%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Chan Joo Lee, Yunbeom Lee, Sungha Park, Seok-Min Kang, Yangsoo Jang, Ji Hyun Lee, Sang-Hak Lee
Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 15 0 R/Contents 16 0 R/TrimBox[0 0 612 792]>>
endobj
15 0 obj
[17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R]
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref001)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref003)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref004)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref001)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref002)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref005)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref006)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref002)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref007)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref008)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref004)>>
endobj
28 0 obj
<>/Border[0 0 0]/A 30 0 R>>
endobj
30 0 obj
<>
endobj
29 0 obj
<>/Border[0 0 0]/A 31 0 R>>
endobj
31 0 obj
<>
endobj
16 0 obj
[32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R]
endobj
32 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
575.9997 666.2299 m
199.9998 666.2299 l
199.9998 666.7299 l
575.9997 666.7299 l
f*
0.83 0.64 0.02 0 k
425.0268 571.5213 m
429.789 571.5213 l
h
f*
435.0047 571.5213 m
439.7102 571.5213 l
h
f*
498.274 558.5386 m
503.0362 558.5386 l
h
f*
461.4236 532.5165 m
466.1858 532.5165 l
h
f*
468.3969 532.5165 m
473.1591 532.5165 l
h
f*
422.022 506.5512 m
426.7843 506.5512 l
h
f*
336.7559 480.5291 m
341.5181 480.5291 l
h
f*
380.8063 441.5244 m
385.5685 441.5244 l
h
f*
405.2976 415.5591 m
410.0598 415.5591 l
h
f*
412.3276 415.5591 m
417.0331 415.5591 l
h
f*
302.9102 337.5496 m
307.6724 337.5496 l
h
f*
232.6677 120.926 m
426.4441 120.926 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(The)Tj
1.9275 0 Td
(common)Tj
4.0222 0 Td
(novelty)Tj
3.3538 0 Td
(of)Tj
1.0444 0 Td
(variants)Tj
3.682 0 Td
(suggested)Tj
4.7801 0 Td
(polymorphism)Tj
6.3794 0 Td
(of)Tj
1.0444 0 Td
(the)Tj
1.5993 0 Td
(two)Tj
1.7605 0 Td
(genes)Tj
2.9122 0 Td
(among)Tj
3.2464 0 Td
(them.)Tj
-35.7522 -1.474 Td
(Our)Tj
1.8738 0 Td
(results)Tj
3.133 0 Td
(provide)Tj
3.4553 0 Td
(rare)Tj
1.9812 0 Td
(genetic)Tj
3.4016 0 Td
(information)Tj
5.1083 0 Td
(associated)Tj
4.9472 0 Td
(with)Tj
1.9753 0 Td
(this)Tj
1.7545 0 Td
(lipid)Tj
1.9634 0 Td
(phenotype)Tj
4.8338 0 Td
(in)Tj
0.9846 0 Td
(East)Tj
-35.412 -1.474 Td
(Asian)Tj
2.6914 0 Td
(people.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 602.5889 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 585.6377 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Individuals)Tj
4.7224 0 Td
(with)Tj
1.9956 0 Td
(hypobetalipoproteinemia)Tj
10.3067 0 Td
(have)Tj
2.058 0 Td
(3040%)Tj
3.3958 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0375 0 Td
(low-density)Tj
4.8869 0 Td
(lipoprotein-)Tj
-32.5188 -1.3039 Td
(cholesterol)Tj
4.5524 0 Td
(\(LDL-C\))Tj
3.7303 0 Td
(levels,)Tj
2.5966 0 Td
(when)Tj
2.4037 0 Td
(they)Tj
1.9276 0 Td
(are)Tj
1.4456 0 Td
(heterozygous.[)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(])Tj
7.8746 0 Td
(Additionally,)Tj
5.4538 0 Td
(they)Tj
1.9276 0 Td
(can)Tj
1.6271 0 Td
(show)Tj
-33.5393 -1.2982 Td
(LDL-C)Tj
3.0443 0 Td
(levels)Tj
/F14 1 Tf
0 Tc
2.3755 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(5)Tj
1.4683 0 Td
(percentile)Tj
4.1612 0 Td
(or)Tj
/F14 1 Tf
0 Tc
1.0999 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(50)Tj
1.9445 0 Td
(mg/dL)Tj
2.897 0 Td
(without)Tj
3.3335 0 Td
(lipid-lowering)Tj
5.9074 0 Td
(therapy.[)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(])Tj
4.6261 0 Td
(In)Tj
1.1112 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
-35.3364 -1.2983 Td
(homozygous)Tj
5.3064 0 Td
(variants,)Tj
3.617 0 Td
(LDL-C)Tj
3.0443 0 Td
(levels)Tj
2.3755 0 Td
(are)Tj
1.4513 0 Td
(known)Tj
3.0047 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(much)Tj
2.5171 0 Td
(lower.)Tj
2.6759 0 Td
(Although)Tj
4.0025 0 Td
(the)Tj
1.474 0 Td
(patients)Tj
3.3676 0 Td
(are)Tj
-35.0133 -1.3039 Td
(often)Tj
2.2847 0 Td
(asymptomatic,)Tj
6.0774 0 Td
(some)Tj
2.3301 0 Td
(have)Tj
2.0636 0 Td
(increased)Tj
3.9968 0 Td
(risk)Tj
1.7178 0 Td
(for)Tj
1.389 0 Td
(steatohepatitis.[)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(])Tj
8.0163 0 Td
(This)Tj
1.9842 0 Td
(phenotype)Tj
4.439 0 Td
(is)Tj
0.8504 0 Td
(asso-)Tj
-35.1493 -1.2983 Td
(ciated)Tj
2.5908 0 Td
(with)Tj
2.0012 0 Td
(variants)Tj
3.3846 0 Td
(of)Tj
/F15 1 Tf
1.0148 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(or)Tj
1.0999 0 Td
(P)Tj
/F15 1 Tf
[()8()]TJ
/F8 1 Tf
(.)Tj
3.1861 0 Td
(Even)Tj
2.2167 0 Td
(common)Tj
3.8437 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(two)Tj
1.7121 0 Td
(genes)Tj
2.4434 0 Td
(may)Tj
1.9276 0 Td
(affect)Tj
-33.9815 -1.2982 Td
(the)Tj
1.4683 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(LDL-C,)Tj
3.2712 0 Td
(although)Tj
3.753 0 Td
(this)Tj
1.6781 0 Td
(effect)Tj
2.3641 0 Td
(can)Tj
1.6214 0 Td
(be)Tj
1.1509 0 Td
(modest.[)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(])Tj
-17.501 -1.304 Td
(In)Tj
1.1111 0 Td
(a)Tj
0.652 0 Td
(Canadian)Tj
4.0819 0 Td
(database,)Tj
3.8607 0 Td
(120)Tj
1.6498 0 Td
(variants)Tj
3.3845 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
1.7292 0 Td
(29)Tj
1.1735 0 Td
(variants)Tj
3.3845 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()8()]TJ
/F8 1 Tf
(,)Tj
3.1805 0 Td
(with)Tj
1.9955 0 Td
(disease-caus-)Tj
-32.1616 -1.2982 Td
(ing)Tj
1.5023 0 Td
(potential,)Tj
3.9855 0 Td
(have)Tj
2.0579 0 Td
(been)Tj
2.1203 0 Td
(reported.[)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(])Tj
5.0457 0 Td
(In)Tj
1.1055 0 Td
(affected)Tj
3.3278 0 Td
(patients,)Tj
3.5943 0 Td
(mutated)Tj
/F15 1 Tf
3.549 0 Td
[()13()]TJ
/F8 1 Tf
2.6815 0 Td
(can)Tj
1.6271 0 Td
(induce)Tj
2.9424 0 Td
(truncated)Tj
-33.5393 -1.2983 Td
(forms)Tj
2.5681 0 Td
(of)Tj
1.0148 0 Td
(apolipoprotein)Tj
6.1455 0 Td
(B)Tj
0.7994 0 Td
(\(apoB\),)Tj
3.1634 0 Td
(which)Tj
2.6532 0 Td
(are)Tj
1.4457 0 Td
(short)Tj
2.2847 0 Td
(enough)Tj
3.2201 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(degradated.)Tj
4.8812 0 Td
(Mutated)Tj
/F15 1 Tf
3.617 0 Td
[()8()]TJ
/F8 1 Tf
-33.9701 -1.2983 Td
(causes)Tj
2.7495 0 Td
(less)Tj
1.6101 0 Td
(degradation)Tj
5.023 0 Td
(of)Tj
1.0148 0 Td
(LDL)Tj
2.0352 0 Td
(receptors)Tj
3.9175 0 Td
(and)Tj
1.7291 0 Td
(increases)Tj
3.8324 0 Td
(the)Tj
1.4684 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2564 0 Td
(receptors)Tj
3.9174 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
-35.2627 -1.3039 Td
(cell,)Tj
1.7858 0 Td
(thereby)Tj
3.2258 0 Td
(reducing)Tj
3.77 0 Td
(blood)Tj
2.5172 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(LDL-C.[)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(])Tj
4.4277 0 Td
(Although)Tj
4.0025 0 Td
(the)Tj
1.4683 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0375 0 Td
(LDL-C)Tj
3.0444 0 Td
(by)Tj
1.1848 0 Td
(a)Tj
0.652 0 Td
(variant)Tj
-34.6221 -1.2982 Td
(of)Tj
1.0147 0 Td
(a)Tj
0.652 0 Td
(specific)Tj
3.1918 0 Td
(gene)Tj
2.0806 0 Td
(may)Tj
1.9276 0 Td
(not)Tj
1.576 0 Td
(be)Tj
1.1509 0 Td
(large,)Tj
2.3811 0 Td
(its)Tj
1.1508 0 Td
(impact)Tj
2.9764 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(cardiovascular)Tj
6.0037 0 Td
(outcome)Tj
3.7304 0 Td
(can)Tj
1.6214 0 Td
(be)Tj
1.1509 0 Td
(greater)Tj
-33.3522 -1.2983 Td
(than)Tj
2.0295 0 Td
(that)Tj
1.7745 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(LDL-C)Tj
3.0444 0 Td
(level)Tj
2.0126 0 Td
(assessed)Tj
3.4753 0 Td
(in)Tj
1.0318 0 Td
(adulthood.[)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(])Tj
6.4062 0 Td
(Therefore,)Tj
4.3937 0 Td
(screening)Tj
4.0535 0 Td
(of)Tj
1.0148 0 Td
(variants)Tj
-31.7251 -1.3039 Td
(related)Tj
2.9423 0 Td
(to)Tj
1.0261 0 Td
(lipid)Tj
2.0466 0 Td
(metabolism)Tj
4.9039 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6577 0 Td
(population)Tj
4.5864 0 Td
(with)Tj
2.0012 0 Td
(extreme)Tj
3.4413 0 Td
(LDL-C)Tj
3.05 0 Td
(levels)Tj
2.3755 0 Td
(can)Tj
1.627 0 Td
(be)Tj
1.1452 0 Td
(a)Tj
0.6577 0 Td
(tool)Tj
1.7801 0 Td
(to)Tj
1.0205 0 Td
(identify)Tj
-34.2933 -1.2983 Td
(an)Tj
1.2018 0 Td
(important)Tj
4.2803 0 Td
(target)Tj
2.5115 0 Td
(affecting)Tj
3.6567 0 Td
(clinical)Tj
3.0727 0 Td
(outcomes.)Tj
-13.5268 -1.2982 Td
(Here,)Tj
2.4321 0 Td
(the)Tj
1.474 0 Td
(aim)Tj
1.7404 0 Td
(of)Tj
1.0148 0 Td
(our)Tj
1.6214 0 Td
(study)Tj
2.3925 0 Td
(was)Tj
1.7007 0 Td
(to)Tj
1.0205 0 Td
(examine)Tj
3.6057 0 Td
(the)Tj
1.4683 0 Td
(prevalence)Tj
4.4844 0 Td
(and)Tj
1.7291 0 Td
(characteristics)Tj
5.9074 0 Td
(of)Tj
1.0148 0 Td
(rare)Tj
1.8198 0 Td
(and)Tj
-34.6221 -1.304 Td
(common)Tj
3.8437 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
/F15 1 Tf
1.0148 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
/F15 1 Tf
1.7292 0 Td
[()8()]TJ
/F8 1 Tf
2.9536 0 Td
(underlying)Tj
4.5978 0 Td
(the)Tj
1.4684 0 Td
(phenotype)Tj
4.439 0 Td
(of)Tj
1.0148 0 Td
(hypobetalipoproteinemia)Tj
-27.1387 -1.2982 Td
(in)Tj
1.0318 0 Td
(Korean)Tj
3.1804 0 Td
(subjects.)Tj
3.6057 0 Td
(We)Tj
1.61 0 Td
(used)Tj
2.058 0 Td
(targeted)Tj
3.4639 0 Td
(next-generation)Tj
6.5933 0 Td
(sequencing,)Tj
4.9379 0 Td
(which)Tj
2.6533 0 Td
(is)Tj
0.8447 0 Td
(becoming)Tj
4.1839 0 Td
(wide-)Tj
-34.1629 -1.2983 Td
(spread)Tj
2.8516 0 Td
(in)Tj
1.0375 0 Td
(genetic)Tj
3.067 0 Td
(studies.[)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(])Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 300.0188 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.5023 Td
(Study)Tj
2.7543 0 Td
(population)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 264.9826 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(Institutional)Tj
5.1647 0 Td
(Review)Tj
3.0954 0 Td
(Board)Tj
2.6362 0 Td
(of)Tj
1.0148 0 Td
(Severance)Tj
4.2009 0 Td
(Hospital)Tj
3.617 0 Td
(approved)Tj
3.9742 0 Td
(the)Tj
1.4683 0 Td
(study)Tj
2.3867 0 Td
(protocols,)Tj
4.184 0 Td
(and)Tj
1.7348 0 Td
(all)Tj
-35.2571 -1.2982 Td
(subjects)Tj
3.3788 0 Td
(provided)Tj
3.8154 0 Td
(written)Tj
3.1125 0 Td
(informed)Tj
3.9684 0 Td
(consent.)Tj
3.5603 0 Td
(Subjects)Tj
3.4923 0 Td
(with)Tj
1.9956 0 Td
(extremely)Tj
4.1442 0 Td
(low)Tj
1.6611 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(LDL-C)Tj
3.0444 0 Td
(were)Tj
-35.5632 -1.2983 Td
(included)Tj
3.7133 0 Td
(in)Tj
1.0318 0 Td
(this)Tj
1.6781 0 Td
(study.)Tj
2.6135 0 Td
(Between)Tj
3.6 0 Td
(November)Tj
4.4617 0 Td
(2000)Tj
2.126 0 Td
(and)Tj
1.7291 0 Td
(March)Tj
2.8687 0 Td
(2011,)Tj
2.347 0 Td
(13,545)Tj
2.8233 0 Td
(subjects)Tj
3.3789 0 Td
(were)Tj
-32.3714 -1.3039 Td
(enrolled)Tj
3.5149 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(Cardiovascular)Tj
6.2418 0 Td
(Genome)Tj
3.6567 0 Td
(Center)Tj
2.948 0 Td
(Cohort,)Tj
3.3222 0 Td
(Yonsei)Tj
2.9594 0 Td
(University)Tj
4.3993 0 Td
(College)Tj
3.1975 0 Td
(of)Tj
1.0148 0 Td
(Medi-)Tj
-33.7604 -1.2983 Td
(cine,)Tj
2.1089 0 Td
(Seoul,)Tj
2.6249 0 Td
(Korea.)Tj
2.8516 0 Td
(Men)Tj
2.0863 0 Td
(and)Tj
1.7291 0 Td
(women)Tj
/F7 1 Tf
0 Tc
3.2032 0 Td
()Tj
/F8 1 Tf
-0.004 Tc
(18)Tj
1.9445 0 Td
(years)Tj
2.262 0 Td
(were)Tj
2.126 0 Td
(recruited)Tj
3.8494 0 Td
(in)Tj
1.0375 0 Td
(this)Tj
1.6724 0 Td
(cohort)Tj
2.8573 0 Td
(when)Tj
2.4038 0 Td
(they)Tj
1.9219 0 Td
(visited)Tj
-34.6788 -1.2982 Td
(Severance)Tj
4.1952 0 Td
(Hospital)Tj
3.6227 0 Td
(for)Tj
1.3833 0 Td
(cardiovascular)Tj
6.0037 0 Td
(diseases,)Tj
3.6056 0 Td
(control)Tj
3.1181 0 Td
(of)Tj
1.0148 0 Td
(risk)Tj
1.7178 0 Td
(factors,)Tj
3.1294 0 Td
(or)Tj
1.0942 0 Td
(health)Tj
2.6816 0 Td
(check-up.)Tj
4.1329 0 Td
(Par-)Tj
-35.6993 -1.3039 Td
(ticipants)Tj
3.6339 0 Td
(were)Tj
2.1203 0 Td
(interviewed)Tj
4.9096 0 Td
(about)Tj
2.4945 0 Td
(their)Tj
2.109 0 Td
(medical)Tj
3.3618 0 Td
(histories,)Tj
3.8324 0 Td
(and)Tj
1.7292 0 Td
(then)Tj
2.0182 0 Td
(underwent)Tj
4.5694 0 Td
(physical)Tj
3.4526 0 Td
(exami-)Tj
-34.2309 -1.2983 Td
(nations.)Tj
3.4072 0 Td
(Among)Tj
3.2485 0 Td
(the)Tj
1.4683 0 Td
(total)Tj
2.0012 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(subjects,)Tj
3.6056 0 Td
(22)Tj
1.1679 0 Td
(subjects,)Tj
3.6057 0 Td
(whose)Tj
2.7212 0 Td
(LDL-C)Tj
3.0501 0 Td
(levels)Tj
2.3754 0 Td
(were)Tj
/F7 1 Tf
0 Tc
2.1203 0 Td
()Tj
/F8 1 Tf
-0.004 Tc
(1)Tj
-33.2048 -1.2983 Td
(percentile)Tj
4.1612 0 Td
(\(48)Tj
1.5137 0 Td
(mg/dL\))Tj
3.2371 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(general)Tj
3.1351 0 Td
(Korean)Tj
3.1804 0 Td
(population,)Tj
4.8132 0 Td
(were)Tj
2.1203 0 Td
(finally)Tj
2.7099 0 Td
(analyzed.)Tj
3.9231 0 Td
(These)Tj
2.5682 0 Td
(22)Tj
1.1735 0 Td
(sub-)Tj
-35.0189 -1.2982 Td
(jects)Tj
1.9842 0 Td
(were)Tj
2.1203 0 Td
(free)Tj
1.7234 0 Td
(from)Tj
2.2111 0 Td
(hypolipidemic)Tj
5.981 0 Td
(treatment)Tj
4.1386 0 Td
(before)Tj
2.7382 0 Td
(or)Tj
1.0999 0 Td
(after)Tj
2.0352 0 Td
(enrollment)Tj
4.6545 0 Td
(to)Tj
1.0204 0 Td
(our)Tj
1.6271 0 Td
(study.)Tj
2.6192 0 Td
(This)Tj
1.9843 0 Td
(cut-)Tj
-35.9374 -1.304 Td
(off)Tj
1.3039 0 Td
(value)Tj
2.3017 0 Td
(is)Tj
0.8504 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(data)Tj
1.9162 0 Td
(from)Tj
2.2053 0 Td
(2011)Tj
2.1204 0 Td
(Korea)Tj
2.6305 0 Td
(National)Tj
3.6907 0 Td
(Health)Tj
2.9196 0 Td
(and)Tj
1.7292 0 Td
(Nutrition)Tj
4.0421 0 Td
(Examination)Tj
-30.9257 -1.2982 Td
(Survey)Tj
2.9253 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(https://knhanes.cdc.)Tj
8.3962 0 Td
(go.kr/knhanes/eng/index.do)Tj
0 g
(\).)Tj
12.1095 0 Td
(The)Tj
1.7801 0 Td
(level)Tj
2.0126 0 Td
(of)Tj
1.0148 0 Td
(LDL-C)Tj
3.0501 0 Td
(was)Tj
1.6951 0 Td
(assessed)Tj
3.4752 0 Td
(by)Tj
-36.4589 -1.2983 Td
(direct)Tj
2.5284 0 Td
(measurement.)Tj
5.8961 0 Td
(Individuals)Tj
4.7225 0 Td
(with)Tj
2.0012 0 Td
(diagnosis)Tj
3.9571 0 Td
(of)Tj
1.0148 0 Td
(thyroid-,)Tj
3.7474 0 Td
(liver-,)Tj
2.5625 0 Td
(or)Tj
1.0942 0 Td
(kidney)Tj
2.9423 0 Td
(disease,)Tj
3.2428 0 Td
(preg-)Tj
-33.7093 -1.3039 Td
(nancy,)Tj
2.8516 0 Td
(cancer,)Tj
3.0727 0 Td
(or)Tj
1.0999 0 Td
(prescribed)Tj
4.4106 0 Td
(regimens)Tj
3.9005 0 Td
(that)Tj
1.7801 0 Td
(could)Tj
2.4492 0 Td
(affect)Tj
2.3754 0 Td
(lipid)Tj
2.0466 0 Td
(profiles)Tj
3.2031 0 Td
(\(such)Tj
2.3981 0 Td
(as)Tj
1.0148 0 Td
(lipid-modifying)Tj
-30.6026 -1.2983 Td
(agents,)Tj
2.9763 0 Td
(corticosteroids,)Tj
6.3552 0 Td
(or)Tj
1.0999 0 Td
(oral)Tj
1.7801 0 Td
(estrogen\))Tj
3.9572 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(time)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(blood)Tj
2.5172 0 Td
(sampling)Tj
3.8777 0 Td
(were)Tj
2.1204 0 Td
(excluded.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 437.8393 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Genetic)Tj
3.6142 0 Td
(variants)Tj
3.6567 0 Td
(in)Tj
0.9779 0 Td
(extremely)Tj
4.4859 0 Td
(low)Tj
1.6866 0 Td
(LDL-C)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01864)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(16,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(13)Tj
/F11 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(Research)Tj
3.6992 0 Td
(Council)Tj
2.9693 0 Td
(of)Tj
0.9496 0 Td
(Science)Tj
3.0969 0 Td
(&)Tj
0.8575 0 Td
(Technology)Tj
4.5213 0 Td
(\(NST\))Tj
-16.0938 -1.3748 Td
(grant)Tj
2.1543 0 Td
(by)Tj
1.1126 0 Td
(the)Tj
1.3677 0 Td
(Korean)Tj
2.8418 0 Td
(government)Tj
4.6984 0 Td
(\(MSIP\))Tj
2.8914 0 Td
(\(No.)Tj
1.8142 0 Td
(CAP-)Tj
-16.8804 -1.3749 Td
(12-2-KBSI\))Tj
4.3937 0 Td
(\(SH)Tj
1.637 0 Td
(Lee\);)Tj
2.0693 0 Td
(and)Tj
1.5874 0 Td
(the)Tj
1.3748 0 Td
(Basic)Tj
2.204 0 Td
(Science)Tj
-13.2662 -1.3748 Td
(Research)Tj
3.6992 0 Td
(Progra)Tj
2.5016 0 Td
(m)Tj
0.9779 0 Td
(through)Tj
3.1465 0 Td
(the)Tj
1.3748 0 Td
(NRF)Tj
1.8142 0 Td
(funded)Tj
2.7922 0 Td
(by)Tj
1.1126 0 Td
(the)Tj
-17.419 -1.3748 Td
(Ministry)Tj
3.2386 0 Td
(of)Tj
0.9496 0 Td
(Science,)Tj
3.3236 0 Td
(ICT)Tj
1.474 0 Td
(and)Tj
1.5875 0 Td
(Future)Tj
2.5724 0 Td
(Planning)Tj
3.4441 0 Td
(\(No:)Tj
-16.5898 -1.3748 Td
(NRF-2015R1A)Tj
5.3858 0 Td
(2A2A030065)Tj
4.8331 0 Td
(77)Tj
1.1693 0 Td
(\(JH)Tj
1.5378 0 Td
(Lee\).)Tj
/F10 1 Tf
-12.926 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F11 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
33 0 obj
<>stream
endstream
endobj
34 0 obj
<>stream
endstream
endobj
35 0 obj
<>stream
endstream
endobj
36 0 obj
<>stream
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
BT
10.3394 73.7155 Td
(exist.)Tj
ET
Q
endstream
endobj
44 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 45 0 R/Contents 46 0 R/TrimBox[0 0 612 792]>>
endobj
45 0 obj
[47 0 R 48 0 R 49 0 R 50 0 R 51 0 R]
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.s001)>>
endobj
48 0 obj
<>/Border[0 0 0]/A 52 0 R>>
endobj
52 0 obj
<>
endobj
49 0 obj
<>/Border[0 0 0]/A 53 0 R>>
endobj
53 0 obj
<>
endobj
50 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.t001)>>
endobj
51 0 obj
<>/Border[0 0 0]/A 54 0 R>>
endobj
54 0 obj
<>
endobj
46 0 obj
[55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R]
endobj
55 0 obj
<>stream
q
0.83 0.64 0.02 0 k
473.1024 484.9512 m
497.4236 484.9512 l
h
f*
500.4283 198.9354 m
560.9764 198.9354 l
h
f*
200.0126 185.9528 m
275.3575 185.9528 l
h
f*
440.1071 107.9433 m
469.3039 107.9433 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Laboratory)Tj
4.9417 0 Td
(assessment)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(total)Tj
2.0069 0 Td
(cholesterol,)Tj
4.7792 0 Td
(triglyceride,)Tj
4.9833 0 Td
(high-density)Tj
5.2384 0 Td
(lipoprotein-cholester)Tj
8.4075 0 Td
(ol)Tj
0.9694 0 Td
(\(HDL-C\),)Tj
4.1839 0 Td
(and)Tj
-35.7389 -1.3039 Td
(LDL-C)Tj
3.0443 0 Td
(were)Tj
2.126 0 Td
(measured)Tj
4.1046 0 Td
(in)Tj
1.0374 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(subjects.)Tj
3.6056 0 Td
(The)Tj
1.7801 0 Td
(subjects)Tj
3.3789 0 Td
(fasted)Tj
2.5569 0 Td
(and)Tj
1.7291 0 Td
(avoided)Tj
3.3618 0 Td
(alcohol)Tj
3.1125 0 Td
(for)Tj
1.3833 0 Td
(at)Tj
0.9524 0 Td
(least)Tj
-34.7865 -1.2982 Td
(12)Tj
1.1678 0 Td
(hours)Tj
2.5172 0 Td
(before)Tj
2.7382 0 Td
(blood)Tj
2.5172 0 Td
(sampling.)Tj
4.1045 0 Td
(Samples)Tj
3.4979 0 Td
(were)Tj
2.1203 0 Td
(analyzed)Tj
3.7021 0 Td
(within)Tj
2.8119 0 Td
(4)Tj
0.6973 0 Td
(hours)Tj
2.5115 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.652 0 Td
(laboratory)Tj
4.3539 0 Td
(that)Tj
-34.5767 -1.2983 Td
(was)Tj
1.6951 0 Td
(certified)Tj
3.5149 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(Korean)Tj
3.1805 0 Td
(Society)Tj
3.0671 0 Td
(of)Tj
1.0148 0 Td
(Laboratory)Tj
4.6431 0 Td
(Medicine.)Tj
4.2179 0 Td
(Circulating)Tj
4.7338 0 Td
(apoB)Tj
2.2564 0 Td
(\(Roche,)Tj
3.2938 0 Td
(Basel,)Tj
-34.2649 -1.3039 Td
(Switzerland\))Tj
5.2497 0 Td
(and)Tj
1.7291 0 Td
(proprotein)Tj
4.5467 0 Td
(convertase)Tj
4.4674 0 Td
(subtilisin/kexin)Tj
6.4006 0 Td
(type)Tj
1.9162 0 Td
(9)Tj
0.6917 0 Td
(\(PCSK9\))Tj
3.7473 0 Td
(levels)Tj
2.3755 0 Td
(\(R&D)Tj
2.6248 0 Td
(Systems,)Tj
-33.749 -1.2983 Td
(Minneapolis,)Tj
5.4594 0 Td
(MN,)Tj
2.0693 0 Td
(USA\))Tj
2.4605 0 Td
(were)Tj
2.1203 0 Td
(measured)Tj
4.1102 0 Td
(using)Tj
2.3867 0 Td
(ELISA)Tj
2.829 0 Td
(assays.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 594.0283 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Targeted)Tj
4.1764 0 Td
(sequencing)Tj
5.2677 0 Td
(and)Tj
1.8662 0 Td
(variant)Tj
3.1843 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 577.0204 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Two)Tj
2.0182 0 Td
(target)Tj
2.5115 0 Td
(genes)Tj
2.4434 0 Td
(were)Tj
2.1203 0 Td
(sequenced:)Tj
/F15 1 Tf
4.6148 0 Td
[()13()]TJ
/F8 1 Tf
2.6816 0 Td
(\(MIM)Tj
2.6872 0 Td
(107730\))Tj
3.4129 0 Td
(and)Tj
/F15 1 Tf
1.7348 0 Td
[()8()]TJ
/F8 1 Tf
2.948 0 Td
(\(MIM)Tj
2.6872 0 Td
(607786\).)Tj
3.6397 0 Td
(Genomic)Tj
-33.4996 -1.2982 Td
(DNA)Tj
2.3754 0 Td
(was)Tj
1.7007 0 Td
(extracted)Tj
3.8835 0 Td
(from)Tj
2.2053 0 Td
(blood)Tj
2.5172 0 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4684 0 Td
(QiagenDNeasy)Tj
6.2532 0 Td
(kit)Tj
1.2812 0 Td
(\(Qiagen,)Tj
3.6737 0 Td
(Valencia,)Tj
3.9118 0 Td
(CA,)Tj
1.7971 0 Td
(USA\).)Tj
-33.4542 -1.2983 Td
(For)Tj
1.627 0 Td
(mutation)Tj
3.9175 0 Td
(analysis,)Tj
3.5546 0 Td
(a)Tj
0.652 0 Td
(panel)Tj
2.3924 0 Td
(for)Tj
1.3833 0 Td
(targeted)Tj
3.4639 0 Td
(DNA)Tj
2.3754 0 Td
(capture)Tj
3.2145 0 Td
(and)Tj
1.7291 0 Td
(sequencing)Tj
4.7168 0 Td
(was)Tj
1.7008 0 Td
(developed)Tj
4.269 0 Td
(by)Tj
-34.9963 -1.3039 Td
(Celemics,)Tj
4.0705 0 Td
(Inc.)Tj
1.7574 0 Td
(\(Seoul,)Tj
2.9651 0 Td
(Korea\).)Tj
3.1974 0 Td
(Targeted)Tj
3.7757 0 Td
(sequencing)Tj
4.7112 0 Td
(and)Tj
1.7348 0 Td
(variant)Tj
3.0274 0 Td
(analysis)Tj
3.3278 0 Td
(were)Tj
2.1203 0 Td
(conducted)Tj
4.4277 0 Td
(as)Tj
-35.1153 -1.2983 Td
(described.)Tj
4.2746 0 Td
(Briefly,)Tj
3.0784 0 Td
(DNA)Tj
2.3754 0 Td
(fragments,)Tj
4.456 0 Td
(containing)Tj
4.5298 0 Td
(all)Tj
1.1452 0 Td
(coding)Tj
2.9593 0 Td
(exons)Tj
2.5228 0 Td
(and)Tj
1.7291 0 Td
(exon-intron)Tj
5.057 0 Td
(junctions,)Tj
-32.1276 -1.2982 Td
(were)Tj
2.1203 0 Td
(enriched)Tj
3.736 0 Td
(by)Tj
1.1792 0 Td
(solution-based)Tj
6.0888 0 Td
(hybridization)Tj
5.6069 0 Td
(capture,)Tj
3.4412 0 Td
(followed)Tj
3.651 0 Td
(by)Tj
1.1792 0 Td
(sequencing)Tj
4.7168 0 Td
(using)Tj
2.3925 0 Td
(the)Tj
1.4683 0 Td
(Illu-)Tj
-35.5802 -1.2983 Td
(mina)Tj
2.2903 0 Td
(HiSeq)Tj
2.6589 0 Td
(2000)Tj
2.1203 0 Td
(platform)Tj
3.702 0 Td
(\(Illumina,)Tj
4.218 0 Td
(Inc.,)Tj
1.9785 0 Td
(San)Tj
1.6838 0 Td
(Diego,)Tj
2.8403 0 Td
(CA,)Tj
1.7915 0 Td
(USA\).)Tj
2.6815 0 Td
(The)Tj
1.7859 0 Td
(quality)Tj
2.9536 0 Td
(of)Tj
1.0148 0 Td
(next-genera-)Tj
-31.7194 -1.3039 Td
(tion)Tj
1.8425 0 Td
(sequencing)Tj
4.7111 0 Td
(data)Tj
1.9162 0 Td
(including)Tj
4.0422 0 Td
(coverage)Tj
3.719 0 Td
(information)Tj
5.0797 0 Td
(is)Tj
0.8447 0 Td
(presented)Tj
4.1159 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(S1)Tj
1.1735 0 Td
(Fig)Tj
0 g
(.)Tj
1.7008 0 Td
(Analysis)Tj
3.5773 0 Td
(of)Tj
-33.7604 -1.2983 Td
(sequencing)Tj
4.7168 0 Td
(data)Tj
1.9105 0 Td
(was)Tj
1.7008 0 Td
(performed)Tj
4.4674 0 Td
(using)Tj
2.3924 0 Td
(an)Tj
1.2019 0 Td
(in-house)Tj
3.7303 0 Td
(analysis)Tj
3.3279 0 Td
(pipeline.)Tj
3.6567 0 Td
(Briefly,)Tj
3.0727 0 Td
(sequencing)Tj
4.7168 0 Td
(reads)Tj
-34.8942 -1.2982 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.4683 0 Td
(HiSeq)Tj
2.6589 0 Td
(2000)Tj
2.126 0 Td
(raw)Tj
1.7064 0 Td
(data)Tj
1.9162 0 Td
(were)Tj
2.1203 0 Td
(sorted)Tj
2.7099 0 Td
(by)Tj
1.1849 0 Td
(index)Tj
2.4491 0 Td
(and)Tj
1.7292 0 Td
(barcode)Tj
3.4128 0 Td
(sequences.)Tj
4.4447 0 Td
(Sorted)Tj
2.8233 0 Td
(fastq)Tj
2.109 0 Td
(files)Tj
-35.0643 -1.304 Td
(were)Tj
2.1203 0 Td
(aligned)Tj
3.135 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(hg19)Tj
2.16 0 Td
(reference)Tj
3.9175 0 Td
(genome)Tj
3.4072 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4684 0 Td
(Burrows-Wheeler)Tj
7.353 0 Td
(Aligner)Tj
3.2258 0 Td
(\(BWA;)Tj
3.016 0 Td
(ver.)Tj
-34.6901 -1.2982 Td
(0.7.12\))Tj
2.9139 0 Td
(BWA-MEM)Tj
5.1534 0 Td
(algorithm.)Tj
4.3823 0 Td
(Output)Tj
3.1351 0 Td
(SAM)Tj
2.2734 0 Td
(files)Tj
1.8028 0 Td
(were)Tj
2.126 0 Td
(converted)Tj
4.1952 0 Td
(into)Tj
1.8426 0 Td
(BAM)Tj
2.3754 0 Td
(files)Tj
1.8085 0 Td
(and)Tj
1.7291 0 Td
(sorted)Tj
-33.7377 -1.2983 Td
(using)Tj
2.3867 0 Td
(SAMtools)Tj
4.1953 0 Td
(\(ver.)Tj
2.0352 0 Td
(1.1\).)Tj
1.9616 0 Td
(Duplicate)Tj
4.0932 0 Td
(removal)Tj
3.4752 0 Td
(was)Tj
1.7008 0 Td
(performed)Tj
4.4674 0 Td
(with)Tj
1.9956 0 Td
(Picard)Tj
2.8062 0 Td
(tools)Tj
2.1374 0 Td
(\(ver.)Tj
2.0352 0 Td
(1.128\))Tj
-33.2898 -1.3039 Td
(MarkDuplicates.)Tj
6.8711 0 Td
(Realignment)Tj
5.3177 0 Td
(around)Tj
3.1351 0 Td
(known)Tj
3.0048 0 Td
(indel)Tj
2.2336 0 Td
(sites)Tj
1.9333 0 Td
(and)Tj
1.7291 0 Td
(Base)Tj
2.0182 0 Td
(Quality)Tj
3.1975 0 Td
(Score)Tj
2.4208 0 Td
(Recalibration)Tj
-31.8612 -1.2983 Td
(\(BQSR\))Tj
3.3221 0 Td
(were)Tj
2.1203 0 Td
(performed)Tj
4.4731 0 Td
(using)Tj
2.3867 0 Td
(GATK)Tj
2.9084 0 Td
(\(v3.3.0\))Tj
3.2314 0 Td
(to)Tj
1.0262 0 Td
(create)Tj
2.5908 0 Td
(the)Tj
1.4684 0 Td
(final)Tj
2.0069 0 Td
(BAM)Tj
2.3754 0 Td
(files.)Tj
2.0296 0 Td
(Variants)Tj
3.6283 0 Td
(were)Tj
-33.5676 -1.2982 Td
(called)Tj
2.5171 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4684 0 Td
(GATK)Tj
2.9083 0 Td
(v3.3.0)Tj
2.5512 0 Td
(Unified)Tj
3.2768 0 Td
(Genotyper)Tj
4.4787 0 Td
(algorithm)Tj
4.1556 0 Td
(for)Tj
1.3889 0 Td
(loci)Tj
1.6611 0 Td
(with)Tj
2.0013 0 Td
(sequencing)Tj
4.7111 0 Td
(depth)Tj
-33.5109 -1.3039 Td
(greater)Tj
3.0047 0 Td
(than)Tj
2.0295 0 Td
(or)Tj
1.0999 0 Td
(equal)Tj
2.3584 0 Td
(to)Tj
1.0261 0 Td
(50X.)Tj
2.0466 0 Td
(Analysis)Tj
3.5773 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(splice)Tj
2.4604 0 Td
(regions,)Tj
3.3902 0 Td
(including)Tj
4.0422 0 Td
(sufficient)Tj
3.9118 0 Td
(intronic)Tj
3.4526 0 Td
(bases,)Tj
-34.8829 -1.2983 Td
(was)Tj
1.6951 0 Td
(performed)Tj
4.473 0 Td
(using)Tj
2.3868 0 Td
(Human)Tj
3.3165 0 Td
(Splicing)Tj
3.4355 0 Td
(Finder.)Tj
3.1068 0 Td
(Functional)Tj
4.5524 0 Td
(annotation)Tj
4.6091 0 Td
(of)Tj
1.0148 0 Td
(genetic)Tj
3.0727 0 Td
(variants)Tj
3.3846 0 Td
(was)Tj
-35.0473 -1.2983 Td
(performed)Tj
4.4673 0 Td
(by)Tj
1.1849 0 Td
(ANNOVAR)Tj
5.1193 0 Td
(\(ver.)Tj
2.0353 0 Td
(2014-11-12\).)Tj
5.2951 0 Td
(Functional)Tj
4.5467 0 Td
(effect)Tj
2.3641 0 Td
(predictions)Tj
4.7338 0 Td
(for)Tj
1.3833 0 Td
(single)Tj
2.5342 0 Td
(nucleo-)Tj
-33.664 -1.2982 Td
(tide)Tj
1.7347 0 Td
(variants)Tj
3.3903 0 Td
(were)Tj
2.1203 0 Td
(performed)Tj
4.473 0 Td
(using)Tj
2.3868 0 Td
(SIFT,)Tj
2.3981 0 Td
(PolyPhen-2)Tj
4.8755 0 Td
(and)Tj
1.7291 0 Td
(MutationTaster,)Tj
6.7181 0 Td
(and)Tj
1.7291 0 Td
(matched)Tj
-31.555 -1.304 Td
(against)Tj
3.0273 0 Td
(the)Tj
1.4684 0 Td
(Korean)Tj
3.1804 0 Td
(population)Tj
4.5864 0 Td
(exome)Tj
2.863 0 Td
(data)Tj
1.9106 0 Td
(\(n)Tj
1.1111 0 Td
(=)Tj
0.7994 0 Td
(476\))Tj
1.9842 0 Td
(and)Tj
1.7348 0 Td
(public)Tj
2.7043 0 Td
(databases)Tj
4.0025 0 Td
(of)Tj
1.0148 0 Td
(variants)Tj
3.3902 0 Td
(\(dbSNP)Tj
-33.7774 -1.2982 Td
(138,)Tj
1.8708 0 Td
(Exome)Tj
3.0047 0 Td
(Variant)Tj
3.2655 0 Td
(Server)Tj
2.7439 0 Td
(and)Tj
1.7291 0 Td
(1000)Tj
2.1203 0 Td
(Genome)Tj
3.6624 0 Td
(project)Tj
3.016 0 Td
(SNP)Tj
1.9899 0 Td
([April)Tj
2.6476 0 Td
(2012)Tj
2.1203 0 Td
(release])Tj
3.2428 0 Td
(from)Tj
2.2053 0 Td
(both)Tj
-33.6186 -1.2983 Td
(Asian)Tj
2.5114 0 Td
(and)Tj
1.7348 0 Td
(all-population)Tj
5.862 0 Td
(databases\).)Tj
4.5695 0 Td
(We)Tj
1.61 0 Td
(then)Tj
2.0183 0 Td
(prioritized)Tj
4.4503 0 Td
(variants)Tj
3.3903 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(following)Tj
-32.8249 -1.3039 Td
(criteria:)Tj
3.2995 0 Td
(1\))Tj
1.0374 0 Td
(variants)Tj
3.3902 0 Td
(that)Tj
1.7745 0 Td
(were)Tj
2.126 0 Td
(reported)Tj
3.6567 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(disease-causing)Tj
6.3949 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(Human)Tj
3.3165 0 Td
(Gene)Tj
2.3301 0 Td
(Mutation)Tj
-32.0086 -1.2983 Td
(Database;)Tj
4.0705 0 Td
(2\))Tj
1.0374 0 Td
(disruptive)Tj
4.235 0 Td
(variants)Tj
3.3902 0 Td
(\(nonsense,)Tj
4.5071 0 Td
(splice-site)Tj
4.1555 0 Td
([two)Tj
2.0523 0 Td
(nucleotides)Tj
4.7735 0 Td
(on)Tj
1.2756 0 Td
(either)Tj
2.5341 0 Td
(side)Tj
1.7972 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.8432 -1.2982 Td
(intron/exon)Tj
5.0342 0 Td
(boundary])Tj
4.4391 0 Td
(and)Tj
1.7291 0 Td
(frameshift\))Tj
4.6375 0 Td
(that)Tj
1.7801 0 Td
(were)Tj
2.1203 0 Td
(novel)Tj
2.3981 0 Td
(or)Tj
1.0998 0 Td
(rare;)Tj
2.0466 0 Td
(and)Tj
1.7292 0 Td
(3\))Tj
1.0374 0 Td
(novel)Tj
2.3981 0 Td
(or)Tj
1.0999 0 Td
(rare)Tj
1.8198 0 Td
(missense)Tj
-33.3692 -1.304 Td
(variants)Tj
3.3902 0 Td
(that)Tj
1.7744 0 Td
(were)Tj
2.126 0 Td
(predicted)Tj
3.9968 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(deleterious)Tj
4.5978 0 Td
(by)Tj
1.1792 0 Td
(SIFT,)Tj
2.4038 0 Td
(Polyphen-2)Tj
4.8302 0 Td
(\(HumVar\),)Tj
4.7395 0 Td
(or)Tj
1.0941 0 Td
(Mutation-)Tj
-32.309 -1.2982 Td
(Taster.)Tj
2.9423 0 Td
(Variants)Tj
3.6283 0 Td
(that)Tj
1.7802 0 Td
(met)Tj
1.7631 0 Td
(these)Tj
2.2507 0 Td
(criteria)Tj
3.0784 0 Td
(were)Tj
2.1203 0 Td
(validated)Tj
3.8324 0 Td
(by)Tj
1.1849 0 Td
(bidirectional)Tj
5.3064 0 Td
(Sanger)Tj
2.9367 0 Td
(sequencing)Tj
4.7168 0 Td
(of)Tj
-35.5405 -1.2983 Td
(PCR)Tj
2.0636 0 Td
(amplicons.)Tj
4.5694 0 Td
(Databases)Tj
4.2066 0 Td
(used)Tj
2.0636 0 Td
(for)Tj
1.3833 0 Td
(identity)Tj
3.3052 0 Td
(and)Tj
1.7291 0 Td
(frequency)Tj
4.1896 0 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(variants)Tj
3.3902 0 Td
(included)Tj
3.7134 0 Td
(1000)Tj
-33.0971 -1.3039 Td
(Genomes)Tj
4.0195 0 Td
(Project,)Tj
3.2825 0 Td
(Exome)Tj
3.0047 0 Td
(Sequencing)Tj
4.8302 0 Td
(Project)Tj
3.0614 0 Td
(6500,)Tj
2.347 0 Td
(and)Tj
1.7292 0 Td
(gnomAD)Tj
3.9798 0 Td
(browser)Tj
3.4469 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(http://gnomad.)Tj
-29.7012 -1.2983 Td
(broadinstitute.org/)Tj
0 g
(\).)Tj
8.3167 0 Td
(Variants)Tj
3.634 0 Td
(were)Tj
2.1203 0 Td
(classified)Tj
3.8211 0 Td
(as)Tj
1.0148 0 Td
(rare)Tj
1.8198 0 Td
(when)Tj
2.4038 0 Td
(minor)Tj
2.7326 0 Td
(allele)Tj
2.2394 0 Td
(frequency)Tj
4.1895 0 Td
(\(MAF\))Tj
/F14 1 Tf
0 Tc
3.0047 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(1%,)Tj
-35.2967 -1.2982 Td
(whereas)Tj
3.4412 0 Td
(classified)Tj
3.8211 0 Td
(as)Tj
1.0148 0 Td
(common)Tj
3.8437 0 Td
(when)Tj
2.4038 0 Td
(MAF)Tj
/F7 1 Tf
0 Tc
2.3244 0 Td
()Tj
/F8 1 Tf
-0.004 Tc
(5%)Tj
2.228 0 Td
(in)Tj
1.0318 0 Td
(public)Tj
2.7099 0 Td
(databases.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 144 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
/F0 1 Tf
0 -1.5023 Td
(Clinical)Tj
3.3874 0 Td
(characteristics)Tj
6.5386 0 Td
(of)Tj
1.0488 0 Td
(study)Tj
2.5843 0 Td
(subjects)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 109.0204 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Clinical)Tj
3.3165 0 Td
(characteristics)Tj
5.9017 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(study)Tj
2.3867 0 Td
(subjects)Tj
3.3789 0 Td
(are)Tj
1.4457 0 Td
(described)Tj
4.0535 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0374 0 Td
(Table)Tj
2.4435 0 Td
(1)Tj
0 g
(.)Tj
0.9184 0 Td
(Mean)Tj
2.5172 0 Td
(patient)Tj
3.0103 0 Td
(age)Tj
1.5421 0 Td
(was)Tj
1.7008 0 Td
(52)Tj
-36.1415 -1.3039 Td
(years)Tj
2.262 0 Td
(and)Tj
1.7291 0 Td
(64%)Tj
1.9332 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.1203 0 Td
(males;)Tj
2.7326 0 Td
(14%)Tj
1.9275 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(subjects)Tj
3.3788 0 Td
(had)Tj
1.7121 0 Td
(type)Tj
1.9106 0 Td
(2)Tj
0.6973 0 Td
(diabetes)Tj
3.4639 0 Td
(for)Tj
1.3833 0 Td
(0)Tj
0.6973 0 Td
(to)Tj
1.0262 0 Td
(27)Tj
-35.3081 -1.2982 Td
(years;)Tj
2.4888 0 Td
(the)Tj
1.4683 0 Td
(mean)Tj
2.4491 0 Td
(level)Tj
2.0126 0 Td
(of)Tj
1.0148 0 Td
(LDL-C)Tj
3.0444 0 Td
(was)Tj
1.7008 0 Td
(39.2)Tj
1.8708 0 Td
(mg/dL.)Tj
3.1294 0 Td
(The)Tj
1.7802 0 Td
(patients')Tj
3.583 0 Td
(median)Tj
3.2428 0 Td
(apoB)Tj
2.2563 0 Td
(level)Tj
2.0126 0 Td
(was)Tj
1.7008 0 Td
(53)Tj
1.1679 0 Td
(mg/)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 437.8393 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Genetic)Tj
3.6142 0 Td
(variants)Tj
3.6567 0 Td
(in)Tj
0.9779 0 Td
(extremely)Tj
4.4859 0 Td
(low)Tj
1.6866 0 Td
(LDL-C)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01864)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(16,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
BT
66.402 0 Td
(13)Tj
ET
Q
endstream
endobj
62 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 65 0 R/Contents 66 0 R/TrimBox[0 0 612 792]>>
endobj
65 0 obj
[67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R]
endobj
67 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref009)>>
endobj
68 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref010)>>
endobj
69 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.t001)>>
endobj
70 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.s002)>>
endobj
71 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.t002)>>
endobj
72 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.g001)>>
endobj
73 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.t002)>>
endobj
74 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.t003)>>
endobj
75 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.s002)>>
endobj
76 0 obj
<>/Border[0 0 0]/Dest(Lpone.0186446.t001)>>
endobj
77 0 obj
<>/Border[0 0 0]/A 79 0 R>>
endobj
79 0 obj
<>
endobj
78 0 obj
<>/Border[0 0 0]/A 80 0 R>>
endobj
80 0 obj
<>
endobj
66 0 obj
[81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R 87 0 R 88 0 R 89 0 R 90 0 R 91 0 R]
endobj
81 0 obj
<>stream
q
0.83 0.64 0.02 0 k
443.0551 406.9417 m
447.8173 406.9417 l
h
f*
450.0283 406.9417 m
459.5528 406.9417 l
h
f*
416.9197 393.9591 m
446.1165 393.9591 l
h
f*
325.7008 380.9764 m
352.063 380.9764 l
h
f*
291.685 309.4299 m
320.8252 309.4299 l
h
f*
359.1496 244.4598 m
378.7654 244.4598 l
h
f*
426.2173 244.4598 m
431.0362 244.4598 l
h
f*
450.4819 244.4598 m
455.2441 244.4598 l
h
f*
415.7858 192.4157 m
442.148 192.4157 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 421.0582 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(dL)Tj
1.2869 0 Td
(\(interquartile)Tj
5.5445 0 Td
(range:)Tj
2.6872 0 Td
(3961)Tj
2.6362 0 Td
(mg/dL\).)Tj
3.4696 0 Td
(This)Tj
1.9843 0 Td
(median)Tj
3.2428 0 Td
(value)Tj
2.3074 0 Td
(was)Tj
1.6951 0 Td
(much)Tj
2.5171 0 Td
(lower)Tj
2.4548 0 Td
(than)Tj
2.0296 0 Td
(9097)Tj
2.6362 0 Td
(mg/dL,)Tj
-34.4917 -1.3039 Td
(which)Tj
2.6475 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(reported)Tj
3.6567 0 Td
(in)Tj
1.0374 0 Td
(prior)Tj
2.2564 0 Td
(studies)Tj
2.982 0 Td
(in)Tj
1.0375 0 Td
(healthy)Tj
3.1351 0 Td
(Koreans.[)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
6.0945 0 Td
(The)Tj
1.7801 0 Td
(median)Tj
3.2428 0 Td
(PCSK9)Tj
3.0671 0 Td
(level)Tj
-34.6051 -1.2982 Td
(was)Tj
1.6951 0 Td
(251)Tj
1.6497 0 Td
(ng/mL)Tj
2.9197 0 Td
(\(interquartile)Tj
5.5445 0 Td
(range:)Tj
2.6872 0 Td
(190342)Tj
3.5943 0 Td
(ng/mL\))Tj
3.2599 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
2.7836 0 Td
(1)Tj
0 g
(\).)Tj
1.2585 0 Td
(The)Tj
1.7859 0 Td
(characteristics)Tj
5.9017 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(total)Tj
-35.5632 -1.2983 Td
(cohort)Tj
2.8516 0 Td
(are)Tj
1.4513 0 Td
(shown)Tj
2.846 0 Td
(in)Tj
1.0375 0 Td
(Table)Tj
2.4434 0 Td
(A)Tj
0.9014 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(S1)Tj
1.1679 0 Td
(File)Tj
0 g
(.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 353.537 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Analysis)Tj
3.8976 0 Td
(of)Tj
1.0441 0 Td
(candidate)Tj
4.5024 0 Td
(genes)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 336.5291 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Eight)Tj
2.347 0 Td
(rare)Tj
1.8199 0 Td
(variants)Tj
3.3902 0 Td
(\(five)Tj
1.9899 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
1.7291 0 Td
(three)Tj
2.262 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()8()]TJ
/F8 1 Tf
(\))Tj
3.2938 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(two)Tj
1.7121 0 Td
(candidate)Tj
4.1045 0 Td
(genes)Tj
2.4378 0 Td
(were)Tj
2.126 0 Td
(identi-)Tj
-34.4577 -1.2982 Td
(fied)Tj
1.7234 0 Td
(in)Tj
1.0375 0 Td
(nine)Tj
2.0069 0 Td
(subjects.)Tj
3.6056 0 Td
(Among)Tj
3.2429 0 Td
(all)Tj
1.1451 0 Td
(the)Tj
1.4741 0 Td
(rare)Tj
1.8198 0 Td
(variants,)Tj
3.6113 0 Td
(five)Tj
1.6554 0 Td
(were)Tj
2.1203 0 Td
(novel)Tj
2.3981 0 Td
(and)Tj
1.7348 0 Td
(five)Tj
1.6498 0 Td
(were)Tj
2.1259 0 Td
(suspected)Tj
4.0819 0 Td
(of)Tj
-35.4328 -1.3039 Td
(being)Tj
2.4321 0 Td
(disease-causing)Tj
6.3949 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
2.7779 0 Td
(2)Tj
0 g
(\).)Tj
1.2643 0 Td
(Two)Tj
2.0182 0 Td
(subjects)Tj
3.3789 0 Td
(had)Tj
1.7121 0 Td
(more)Tj
2.3414 0 Td
(than)Tj
2.0296 0 Td
(two)Tj
1.7064 0 Td
(different)Tj
3.6567 0 Td
(rare)Tj
1.8198 0 Td
(variants)Tj
3.3903 0 Td
(in)Tj
-34.9226 -1.2983 Td
(either)Tj
2.5284 0 Td
(gene)Tj
2.0807 0 Td
(\(one)Tj
2.0409 0 Td
(subject)Tj
3.016 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
1.7292 0 Td
(another)Tj
3.3278 0 Td
(subject)Tj
3.0217 0 Td
(in)Tj
/F15 1 Tf
1.0318 0 Td
[()13()]TJ
/F8 1 Tf
(/)Tj
/F15 1 Tf
[()8()]TJ
/F8 1 Tf
(\).)Tj
6.3156 0 Td
(Conversely,)Tj
4.8982 0 Td
(12)Tj
1.1735 0 Td
(com-)Tj
-34.8885 -1.2983 Td
(mon)Tj
2.0919 0 Td
(variants)Tj
3.3902 0 Td
(\(nine)Tj
2.3471 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
1.7291 0 Td
(three)Tj
2.262 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()8()]TJ
/F8 1 Tf
(\))Tj
3.2939 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(genes)Tj
2.4378 0 Td
(were)Tj
2.126 0 Td
(discovered)Tj
4.507 0 Td
(in)Tj
1.0318 0 Td
(21)Tj
1.1736 0 Td
(sub-)Tj
-35.3478 -1.3039 Td
(jects.)Tj
2.2053 0 Td
(Among)Tj
3.2485 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(common)Tj
3.8438 0 Td
(variants,)Tj
3.6169 0 Td
(one)Tj
1.7008 0 Td
(in)Tj
/F15 1 Tf
1.0318 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(was)Tj
1.7008 0 Td
(novel.)Tj
2.6249 0 Td
(Five)Tj
1.8935 0 Td
(common)Tj
3.8438 0 Td
(variants)Tj
3.3902 0 Td
(in)Tj
/F15 1 Tf
-34.401 -1.2982 Td
[()13()]TJ
/F8 1 Tf
2.6815 0 Td
(\(e.g.,)Tj
2.126 0 Td
(c.C8216T)Tj
4.0478 0 Td
([p.P2739L]\))Tj
4.9833 0 Td
(and)Tj
1.7291 0 Td
(two)Tj
1.7121 0 Td
(in)Tj
/F15 1 Tf
1.0318 0 Td
[()8()]TJ
/F8 1 Tf
2.9537 0 Td
(\(e.g.)Tj
1.8992 0 Td
(c.G2009A)Tj
4.1726 0 Td
([p.G670E]\))Tj
4.6941 0 Td
(were)Tj
2.1203 0 Td
(frequent)Tj
-34.1515 -1.2983 Td
(and)Tj
1.7291 0 Td
(found)Tj
2.6192 0 Td
(in)Tj
1.0374 0 Td
(more)Tj
2.3414 0 Td
(than)Tj
2.024 0 Td
(10)Tj
1.1735 0 Td
(individuals)Tj
4.6488 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8198 0 Td
(1)Tj
0 g
0.6973 0 Td
(and)Tj
1.7292 0 Td
(Tables)Tj
0.83 0.64 0.02 0 k
2.8006 0 Td
(2)Tj
0 g
0.6973 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7291 0 Td
(3)Tj
0 g
(\).)Tj
1.2643 0 Td
(Three)Tj
2.5738 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
1.0148 0 Td
(unknown)Tj
-33.2898 -1.3039 Td
(frequency)Tj
4.1839 0 Td
(\(one)Tj
2.0409 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()13()]TJ
/F8 1 Tf
2.6872 0 Td
(and)Tj
1.7291 0 Td
(two)Tj
1.7065 0 Td
(in)Tj
/F15 1 Tf
1.0374 0 Td
[()8()]TJ
/F8 1 Tf
(\))Tj
3.2939 0 Td
(were)Tj
2.1203 0 Td
(identified)Tj
4.0592 0 Td
(in)Tj
1.0374 0 Td
(10)Tj
1.1679 0 Td
(subjects.)Tj
3.6056 0 Td
(One)Tj
1.9389 0 Td
(subject)Tj
3.0161 0 Td
(did)Tj
1.542 0 Td
(not)Tj
-36.2038 -1.2983 Td
(possess)Tj
3.1124 0 Td
(any)Tj
1.6554 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7065 0 Td
(genes.)Tj
2.6702 0 Td
(Analysis)Tj
3.5773 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(splice)Tj
2.4605 0 Td
(regions)Tj
3.1634 0 Td
(revealed)Tj
3.5207 0 Td
(no)Tj
1.2755 0 Td
(variants.)Tj
3.617 0 Td
(The)Tj
-35.1153 -1.2983 Td
(type)Tj
1.9048 0 Td
(of)Tj
1.0091 0 Td
(variants)Tj
3.3846 0 Td
(in)Tj
1.0261 0 Td
(non-diabetic)Tj
5.3178 0 Td
(and)Tj
1.7234 0 Td
(diabetic)Tj
3.3619 0 Td
(subjects)Tj
3.3676 0 Td
(was)Tj
1.6951 0 Td
(analyzed)Tj
3.6963 0 Td
(and)Tj
1.7235 0 Td
(there)Tj
2.2563 0 Td
(was)Tj
1.6895 0 Td
(no)Tj
1.2699 0 Td
(significant)Tj
-33.4259 -1.3039 Td
(difference)Tj
4.2009 0 Td
(therein)Tj
3.084 0 Td
(between)Tj
3.5263 0 Td
(the)Tj
1.4684 0 Td
(two)Tj
1.7121 0 Td
(groups)Tj
2.9707 0 Td
(\(Table)Tj
2.7779 0 Td
(B)Tj
0.7994 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0374 0 Td
(S1)Tj
1.1736 0 Td
(File)Tj
0 g
(\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 164.9763 cm
BT
/F6 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(APOB)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 148.0251 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Five)Tj
1.8935 0 Td
(rare)Tj
1.8198 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
/F15 1 Tf
1.0148 0 Td
[()13()]TJ
/F8 1 Tf
2.6816 0 Td
(were)Tj
2.126 0 Td
(discovered)Tj
4.507 0 Td
(in)Tj
1.0318 0 Td
(seven)Tj
2.4321 0 Td
(subjects:)Tj
3.6057 0 Td
(c.G12016A)Tj
4.6431 0 Td
(\(p.V4006I\),)Tj
4.8075 0 Td
(c.)Tj
-33.9531 -1.3039 Td
(C11120T)Tj
3.8721 0 Td
(\(p.A370V\),)Tj
4.6714 0 Td
(c.C2398A)Tj
4.1216 0 Td
(\(p.L800M\),)Tj
4.7225 0 Td
(c.G1342A)Tj
4.1725 0 Td
(\(p.A448T\),)Tj
4.5921 0 Td
(and)Tj
1.7291 0 Td
(c.T35C)Tj
3.0955 0 Td
(\(p.L12P\).)Tj
3.9174 0 Td
(All)Tj
1.3947 0 Td
(the)Tj
-36.2889 -1.2982 Td
(rare)Tj
1.8198 0 Td
(variants)Tj
3.3902 0 Td
(were)Tj
2.1203 0 Td
(present)Tj
3.1634 0 Td
(in)Tj
1.0375 0 Td
(heterozygous)Tj
5.4992 0 Td
(form.)Tj
2.4321 0 Td
(One)Tj
1.9389 0 Td
(subject)Tj
3.016 0 Td
(showed)Tj
3.2485 0 Td
(three)Tj
2.2677 0 Td
(different)Tj
3.6567 0 Td
(rare)Tj
1.8198 0 Td
(het-)Tj
-35.4101 -1.2983 Td
(erozygous)Tj
4.2462 0 Td
(variants)Tj
3.3902 0 Td
(of)Tj
/F15 1 Tf
1.0148 0 Td
[()13()]TJ
/F8 1 Tf
(,)Tj
2.914 0 Td
(while)Tj
2.3698 0 Td
(one)Tj
1.6951 0 Td
(subject)Tj
3.0217 0 Td
(showed)Tj
3.2485 0 Td
(two)Tj
1.7064 0 Td
(rare)Tj
1.8255 0 Td
(heterozygous)Tj
5.4992 0 Td
(variants)Tj
3.3846 0 Td
(of)Tj
/F15 1 Tf
-34.316 -1.3039 Td
[()13()]TJ
/F8 1 Tf
2.6815 0 Td
(and)Tj
/F15 1 Tf
1.7348 0 Td
[()8()]TJ
/F8 1 Tf
(.)Tj
3.1748 0 Td
(Four)Tj
2.1543 0 Td
(of)Tj
1.0148 0 Td
(five)Tj
1.6554 0 Td
(rare)Tj
1.8199 0 Td
(variants)Tj
3.3902 0 Td
(were)Tj
2.1203 0 Td
(novel,)Tj
2.6248 0 Td
(and)Tj
1.7292 0 Td
(c.G10216A,)Tj
4.8755 0 Td
(c.G2398A,)Tj
4.3937 0 Td
(and)Tj
1.7291 0 Td
(c.)Tj
-35.0983 -1.2983 Td
(T35C)Tj
2.4434 0 Td
(variants)Tj
3.3902 0 Td
(were)Tj
2.1203 0 Td
(predicted)Tj
4.0025 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(damaging.)Tj
4.405 0 Td
(Meanwhile,)Tj
4.8926 0 Td
(seven)Tj
2.4321 0 Td
(common)Tj
3.8437 0 Td
(variants)Tj
3.3903 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
ET
Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
199.9998 703.8893 m
575.9997 703.8893 l
575.9997 703.3893 l
199.9998 703.3893 l
f*
389.7111 703.3893 m
389.7111 690.8893 l
389.211 690.8893 l
389.211 703.3893 l
f*
389.211 690.8893 m
199.9998 690.8893 l
199.9998 691.3894 l
389.211 691.3894 l
f*
575.9994 690.8893 m
389.7111 690.8893 l
389.7111 691.3894 l
575.9994 691.3894 l
f*
389.7111 690.8893 m
389.7111 678.3894 l
389.211 678.3894 l
389.211 690.8893 l
f*
389.211 678.3894 m
199.9998 678.3894 l
199.9998 678.8894 l
389.211 678.8894 l
f*
575.9994 678.3894 m
389.7111 678.3894 l
389.7111 678.8894 l
575.9994 678.8894 l
f*
389.7111 678.3894 m
389.7111 665.8894 l
389.211 665.8894 l
389.211 678.3894 l
f*
389.211 665.8894 m
199.9998 665.8894 l
199.9998 666.3895 l
389.211 666.3895 l
f*
575.9994 665.8894 m
389.7111 665.8894 l
389.7111 666.3895 l
575.9994 666.3895 l
f*
389.7111 665.8894 m
389.7111 653.3895 l
389.211 653.3895 l
389.211 665.8894 l
f*
389.211 653.3895 m
199.9998 653.3895 l
199.9998 653.8895 l
389.211 653.8895 l
f*
575.9994 653.3895 m
389.7111 653.3895 l
389.7111 653.8895 l
575.9994 653.8895 l
f*
389.7111 653.3895 m
389.7111 640.8896 l
389.211 640.8896 l
389.211 653.3895 l
f*
389.211 640.8896 m
199.9998 640.8896 l
199.9998 641.3896 l
389.211 641.3896 l
f*
575.9994 640.8896 m
389.7111 640.8896 l
389.7111 641.3896 l
575.9994 641.3896 l
f*
389.7111 640.8896 m
389.7111 628.3896 l
389.211 628.3896 l
389.211 640.8896 l
f*
389.211 628.3896 m
199.9998 628.3896 l
199.9998 628.8897 l
389.211 628.8897 l
f*
575.9994 628.3896 m
389.7111 628.3896 l
389.7111 628.8897 l
575.9994 628.8897 l
f*
389.7111 628.3896 m
389.7111 615.8897 l
389.211 615.8897 l
389.211 628.3896 l
f*
389.211 615.8897 m
199.9998 615.8897 l
199.9998 616.3897 l
389.211 616.3897 l
f*
575.9994 615.8897 m
389.7111 615.8897 l
389.7111 616.3897 l
575.9994 616.3897 l
f*
389.7111 615.8897 m
389.7111 603.3898 l
389.211 603.3898 l
389.211 615.8897 l
f*
389.211 603.3898 m
199.9998 603.3898 l
199.9998 603.8898 l
389.211 603.8898 l
f*
575.9994 603.3898 m
389.7111 603.3898 l
389.7111 603.8898 l
575.9994 603.8898 l
f*
389.7111 603.3898 m
389.7111 590.8898 l
389.211 590.8898 l
389.211 603.3898 l
f*
389.211 590.8898 m
199.9998 590.8898 l
199.9998 591.3899 l
389.211 591.3899 l
f*
575.9994 590.8898 m
389.7111 590.8898 l
389.7111 591.3899 l
575.9994 591.3899 l
f*
389.7111 590.8898 m
389.7111 578.3899 l
389.211 578.3899 l
389.211 590.8898 l
f*
389.211 578.3899 m
199.9998 578.3899 l
199.9998 578.8899 l
389.211 578.8899 l
f*
575.9994 578.3899 m
389.7111 578.3899 l
389.7111 578.8899 l
575.9994 578.8899 l
f*
389.7111 578.3899 m
389.7111 565.89 l
389.211 565.89 l
389.211 578.3899 l
f*
389.211 565.89 m
199.9998 565.89 l
199.9998 566.39 l
389.211 566.39 l
f*
575.9994 565.89 m
389.7111 565.89 l
389.7111 566.39 l
575.9994 566.39 l
f*
389.7111 565.89 m
389.7111 553.39 l
389.211 553.39 l
389.211 565.89 l
f*
389.211 553.39 m
199.9998 553.39 l
199.9998 553.89 l
389.211 553.89 l
f*
575.9994 553.39 m
389.7111 553.39 l
389.7111 553.89 l
575.9994 553.89 l
f*
389.7111 553.39 m
389.7111 540.8901 l
389.211 540.8901 l
389.211 553.39 l
f*
389.211 540.8901 m
199.9998 540.8901 l
199.9998 541.3901 l
389.211 541.3901 l
f*
575.9994 540.8901 m
389.7111 540.8901 l
389.7111 541.3901 l
575.9994 541.3901 l
f*
389.7111 540.8901 m
389.7111 528.3901 l
389.211 528.3901 l
389.211 540.8901 l
f*
389.211 528.3901 m
199.9998 528.3901 l
199.9998 528.8902 l
389.211 528.8902 l
f*
575.9994 528.3901 m
389.7111 528.3901 l
389.7111 528.8902 l
575.9994 528.8902 l
f*
389.7111 528.3901 m
389.7111 515.8902 l
389.211 515.8902 l
389.211 528.3901 l
f*
389.211 515.8902 m
199.9998 515.8902 l
199.9998 516.3902 l
389.211 516.3902 l
f*
575.9994 515.8902 m
389.7111 515.8902 l
389.7111 516.3902 l
575.9994 516.3902 l
f*
389.7111 515.8902 m
389.7111 503.3903 l
389.211 503.3903 l
389.211 515.8902 l
f*
389.211 503.3903 m
199.9998 503.3903 l
199.9998 503.8903 l
389.211 503.8903 l
f*
575.9994 503.3903 m
389.7111 503.3903 l
389.7111 503.8903 l
575.9994 503.8903 l
f*
575.9994 457.6402 m
199.9998 457.6402 l
199.9998 458.1403 l
575.9994 458.1403 l
f*
0.83 0.64 0.02 0 k
200.0126 444.5858 m
350.7591 444.5858 l
h
f*
0 g
7.9999 0 0 7.9999 200.0125 708.7181 cm
BT
/F3 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.7992 0 Td
(1.)Tj
1.2614 0 Td
(Clinical)Tj
3.7276 0 Td
(characterist)Tj
5.5701 0 Td
(ics)Tj
1.5874 0 Td
(of)Tj
1.1552 0 Td
(study)Tj
2.8559 0 Td
(subjects)Tj
3.9969 0 Td
(.)Tj
0 Tc
-22.9537 -1.8567 Td
(Variable)Tj
3.8693 0 Td
(s)Tj
26.1427 0 Td
(Study)Tj
2.9977 0 Td
(subjects)Tj
4.2732 0 Td
(\(n)Tj
1.1764 0 Td
(=)Tj
0.8079 0 Td
(22\))Tj
/F0 1 Tf
-39.2672 -1.559 Td
(Age,)Tj
2.2748 0 Td
(years)Tj
30.6498 0 Td
(52.1)Tj
/F9 1 Tf
2.1615 0 Td
[( )]TJ
/F0 1 Tf
0.7724 0 Td
(16.3)Tj
-35.8585 -1.5662 Td
(Male)Tj
33.8105 0 Td
(14)Tj
1.3252 0 Td
(\(64\))Tj
-35.1357 -1.559 Td
(Medical)Tj
3.6425 0 Td
(history)Tj
-2.7213 -1.5662 Td
(Hyperte)Tj
3.4725 0 Td
(nsion)Tj
29.4168 0 Td
(12)Tj
1.3252 0 Td
(\(55\))Tj
-34.2145 -1.5591 Td
(Type)Tj
2.4378 0 Td
(2)Tj
0.7796 0 Td
(diabetes)Tj
29.9411 0 Td
(3)Tj
0.7867 0 Td
(\(14\))Tj
-33.9452 -1.559 Td
(Curren)Tj
3.026 0 Td
(t)Tj
0.5103 0 Td
(smoker)Tj
29.6222 0 Td
(7)Tj
0.7867 0 Td
(\(32\))Tj
-34.8664 -1.5662 Td
(Body)Tj
2.4945 0 Td
(mass)Tj
2.6079 0 Td
(index,)Tj
2.8771 0 Td
(kg/m)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 281.1401 609.959 cm
BT
/F0 1 Tf
1 TL
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 465.6188 606.3874 cm
BT
/F0 1 Tf
1 TL
0 0 Td
(23.5)Tj
/F9 1 Tf
2.1614 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(2.8)Tj
-36.1277 -1.559 Td
(Laborato)Tj
3.9118 0 Td
(ry)Tj
1.063 0 Td
(values)Tj
-4.0535 -1.5662 Td
(Total)Tj
2.4378 0 Td
(cholestero)Tj
4.578 0 Td
(l,)Tj
0.7299 0 Td
(mg/dL)Tj
24.8103 0 Td
(124)Tj
/F9 1 Tf
1.8851 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(21)Tj
-35.2064 -1.559 Td
(TG,)Tj
1.8992 0 Td
(mg/dL)Tj
29.7427 0 Td
(185)Tj
1.885 0 Td
(\(96,269\))Tj
-33.5269 -1.5662 Td
(HDL-C)Tj
3.026 0 Td
(,)Tj
0.5102 0 Td
(mg/dL)Tj
28.4672 0 Td
(48.3)Tj
/F9 1 Tf
2.1613 0 Td
[( )]TJ
/F0 1 Tf
0.7725 0 Td
(17.4)Tj
-34.9372 -1.5591 Td
(LDL-C,)Tj
3.3732 0 Td
(mg/dL)Tj
28.9065 0 Td
(39.2)Tj
/F9 1 Tf
2.1614 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(7.1)Tj
-35.2064 -1.5661 Td
(Non-HD)Tj
3.5787 0 Td
(L-C,)Tj
2.1119 0 Td
(mg/dL)Tj
27.1418 0 Td
(75)Tj
/F9 1 Tf
1.3323 0 Td
[( )]TJ
/F0 1 Tf
0.7725 0 Td
(16)Tj
-34.9372 -1.5591 Td
(apoB,)Tj
2.8205 0 Td
(mg/dL)Tj
29.2608 0 Td
(53)Tj
1.3322 0 Td
(\(39,)Tj
1.9418 0 Td
(61\))Tj
-35.3553 -1.5661 Td
(PCSK9,)Tj
3.7701 0 Td
(ng/mL)Tj
27.4821 0 Td
(251)Tj
1.8849 0 Td
(\(190,)Tj
2.4945 0 Td
(342\))Tj
-36.5529 -2.3457 Td
(Values)Tj
3.2599 0 Td
(are)Tj
1.6653 0 Td
(presented)Tj
4.6418 0 Td
(as)Tj
1.2756 0 Td
(mean)Tj
/F9 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7724 0 Td
(SD,)Tj
1.8922 0 Td
(n)Tj
0.7795 0 Td
(\(%\),)Tj
2.0552 0 Td
(or)Tj
1.1126 0 Td
(median)Tj
3.4795 0 Td
(\(interquar)Tj
4.2449 0 Td
(tile)Tj
1.5024 0 Td
(range\);)Tj
3.3733 0 Td
(TG:)Tj
1.8991 0 Td
(triglyceride)Tj
4.7977 0 Td
(;)Tj
0.5102 0 Td
(HDL-C:)Tj
3.5433 0 Td
(high-)Tj
-43.5191 -1.4953 Td
(density)Tj
3.3733 0 Td
(lipoprotein-c)Tj
5.4 0 Td
(holesterol;)Tj
4.8118 0 Td
(LDL-C:)Tj
3.3733 0 Td
(low-densit)Tj
4.4646 0 Td
(y)Tj
0.7299 0 Td
(lipoprotein-c)Tj
5.4001 0 Td
(holesterol;)Tj
4.8118 0 Td
(apoB:)Tj
2.8204 0 Td
(apolipopro)Tj
4.6205 0 Td
(tein)Tj
1.8355 0 Td
(B;)Tj
1.1693 0 Td
(PCSK9:)Tj
-42.8105 -1.5024 Td
(proprote)Tj
3.6922 0 Td
(in)Tj
0.9992 0 Td
(convertas)Tj
4.3087 0 Td
(e)Tj
0.7866 0 Td
(subtilis)Tj
3.026 0 Td
(in/kexin)Tj
3.6 0 Td
(type)Tj
2.1048 0 Td
(9.)Tj
0.83 0.64 0.02 0 k
/F11 1 Tf
-0.025 Tc
-18.5175 -2.2465 Td
(https://d)Tj
3.0827 0 Td
(oi.org/10.1371/j)Tj
5.9174 0 Td
(ournal.pon)Tj
3.9827 0 Td
(e.0186446.t00)Tj
5.3858 0 Td
(1)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 437.8393 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Genetic)Tj
3.6142 0 Td
(variants)Tj
3.6567 0 Td
(in)Tj
0.9779 0 Td
(extremely)Tj
4.4859 0 Td
(low)Tj
1.6866 0 Td
(LDL-C)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01864)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(16,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(4)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
82 0 obj
<>stream
endstream
endobj
83 0 obj
<>stream
endstream
endobj
84 0 obj
<>stream
endstream
endobj
85 0 obj
<>stream
endstream
endobj
86 0 obj
<>stream
endstream
endobj
87 0 obj
<>stream
endstream
endobj
88 0 obj
<>stream
endstream
endobj
89 0 obj
<>stream
endstream
endobj
90 0 obj
<>stream
endstream
endobj
91 0 obj
<>stream
BT
66.402 0 Td
(13)Tj
ET
Q
endstream
endobj
92 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 94 0 R/Contents 95 0 R/TrimBox[0 0 612 792]>>
endobj
94 0 obj
[96 0 R 97 0 R 98 0 R 99 0 R 100 0 R]
endobj
96 0 obj
<>/Border[0 0 0]/Dest(Lpone.0186446.t002)>>
endobj
97 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref011)>>
endobj
98 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref011)>>
endobj
99 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref011)>>
endobj
100 0 obj
<>/Border[0 0 0]/A 101 0 R>>
endobj
101 0 obj
<>
endobj
95 0 obj
[102 0 R 103 0 R 104 0 R]
endobj
102 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
49.0289 83.2859 m
49.0289 713.2859 l
49.5289 713.2859 l
49.5289 83.2859 l
f*
49.5289 109.7212 m
95.0287 109.7212 l
95.0287 109.2212 l
49.5289 109.2212 l
f*
95.0287 109.2212 m
95.0287 83.2859 l
94.5286 83.2859 l
94.5286 109.2212 l
f*
49.5289 154.8479 m
95.0287 154.8479 l
95.0287 154.3479 l
49.5289 154.3479 l
f*
95.0287 154.3479 m
95.0287 109.7212 l
94.5286 109.7212 l
94.5286 154.3479 l
f*
49.5289 239.5772 m
95.0287 239.5772 l
95.0287 239.0771 l
49.5289 239.0771 l
f*
95.0287 239.0771 m
95.0287 154.8479 l
94.5286 154.8479 l
94.5286 239.0771 l
f*
49.5289 300.873 m
95.0287 300.873 l
95.0287 300.3729 l
49.5289 300.3729 l
f*
95.0287 300.3729 m
95.0287 239.5772 l
94.5286 239.5772 l
94.5286 300.3729 l
f*
49.5289 362.0772 m
95.0287 362.0772 l
95.0287 361.5772 l
49.5289 361.5772 l
f*
95.0287 361.5772 m
95.0287 300.873 l
94.5286 300.873 l
94.5286 361.5772 l
f*
49.5289 403.8049 m
95.0287 403.8049 l
95.0287 403.3049 l
49.5289 403.3049 l
f*
95.0287 403.3049 m
95.0287 362.0772 l
94.5286 362.0772 l
94.5286 403.3049 l
f*
49.5289 457.0778 m
95.0287 457.0778 l
95.0287 456.5778 l
49.5289 456.5778 l
f*
95.0287 456.5778 m
95.0287 403.8049 l
94.5286 403.8049 l
94.5286 456.5778 l
f*
49.5289 499.7735 m
95.0287 499.7735 l
95.0287 499.2735 l
49.5289 499.2735 l
f*
95.0287 499.2735 m
95.0287 457.0778 l
94.5286 457.0778 l
94.5286 499.2735 l
f*
49.5289 544.2854 m
95.0287 544.2854 l
95.0287 543.7854 l
49.5289 543.7854 l
f*
95.0287 543.7854 m
95.0287 499.7735 l
94.5286 499.7735 l
94.5286 543.7854 l
f*
49.5289 634.0493 m
95.0287 634.0493 l
95.0287 633.5493 l
49.5289 633.5493 l
f*
95.0287 633.5493 m
95.0287 544.2854 l
94.5286 544.2854 l
94.5286 633.5493 l
f*
95.0287 713.2859 m
95.0287 634.0493 l
94.5286 634.0493 l
94.5286 713.2859 l
f*
95.0287 109.7212 m
106.5285 109.7212 l
106.5285 109.2212 l
95.0287 109.2212 l
f*
106.5285 109.2212 m
106.5285 83.2859 l
106.0285 83.2859 l
106.0285 109.2212 l
f*
106.5285 713.2859 m
106.5285 109.7212 l
106.0285 109.7212 l
106.0285 713.2859 l
f*
106.5285 109.7212 m
135.0283 109.7212 l
135.0283 109.2212 l
106.5285 109.2212 l
f*
135.0283 109.2212 m
135.0283 83.2859 l
134.5283 83.2859 l
134.5283 109.2212 l
f*
106.5285 154.8479 m
135.0283 154.8479 l
135.0283 154.3479 l
106.5285 154.3479 l
f*
135.0283 154.3479 m
135.0283 109.7212 l
134.5283 109.7212 l
134.5283 154.3479 l
f*
106.5285 239.5772 m
135.0283 239.5772 l
135.0283 239.0771 l
106.5285 239.0771 l
f*
135.0283 239.0771 m
135.0283 154.8479 l
134.5283 154.8479 l
134.5283 239.0771 l
f*
106.5285 300.873 m
135.0283 300.873 l
135.0283 300.3729 l
106.5285 300.3729 l
f*
135.0283 300.3729 m
135.0283 239.5772 l
134.5283 239.5772 l
134.5283 300.3729 l
f*
106.5285 362.0772 m
135.0283 362.0772 l
135.0283 361.5772 l
106.5285 361.5772 l
f*
135.0283 361.5772 m
135.0283 300.873 l
134.5283 300.873 l
134.5283 361.5772 l
f*
106.5285 403.8049 m
135.0283 403.8049 l
135.0283 403.3049 l
106.5285 403.3049 l
f*
135.0283 403.3049 m
135.0283 362.0772 l
134.5283 362.0772 l
134.5283 403.3049 l
f*
106.5285 457.0778 m
135.0283 457.0778 l
135.0283 456.5778 l
106.5285 456.5778 l
f*
135.0283 456.5778 m
135.0283 403.8049 l
134.5283 403.8049 l
134.5283 456.5778 l
f*
106.5285 499.7735 m
135.0283 499.7735 l
135.0283 499.2735 l
106.5285 499.2735 l
f*
135.0283 499.2735 m
135.0283 457.0778 l
134.5283 457.0778 l
134.5283 499.2735 l
f*
106.5285 544.2854 m
135.0283 544.2854 l
135.0283 543.7854 l
106.5285 543.7854 l
f*
135.0283 543.7854 m
135.0283 499.7735 l
134.5283 499.7735 l
134.5283 543.7854 l
f*
106.5285 634.0493 m
135.0283 634.0493 l
135.0283 633.5493 l
106.5285 633.5493 l
f*
135.0283 633.5493 m
135.0283 544.2854 l
134.5283 544.2854 l
134.5283 633.5493 l
f*
135.0283 713.2859 m
135.0283 634.0493 l
134.5283 634.0493 l
134.5283 713.2859 l
f*
135.0283 109.7212 m
155.0282 109.7212 l
155.0282 109.2212 l
135.0283 109.2212 l
f*
155.0282 109.2212 m
155.0282 83.2859 l
154.5282 83.2859 l
154.5282 109.2212 l
f*
135.0283 154.8479 m
155.0282 154.8479 l
155.0282 154.3479 l
135.0283 154.3479 l
f*
155.0282 154.3479 m
155.0282 109.7212 l
154.5282 109.7212 l
154.5282 154.3479 l
f*
135.0283 239.5772 m
155.0282 239.5772 l
155.0282 239.0771 l
135.0283 239.0771 l
f*
155.0282 239.0771 m
155.0282 154.8479 l
154.5282 154.8479 l
154.5282 239.0771 l
f*
135.0283 300.873 m
155.0282 300.873 l
155.0282 300.3729 l
135.0283 300.3729 l
f*
155.0282 300.3729 m
155.0282 239.5772 l
154.5282 239.5772 l
154.5282 300.3729 l
f*
135.0283 362.0772 m
155.0282 362.0772 l
155.0282 361.5772 l
135.0283 361.5772 l
f*
155.0282 361.5772 m
155.0282 300.873 l
154.5282 300.873 l
154.5282 361.5772 l
f*
135.0283 403.8049 m
155.0282 403.8049 l
155.0282 403.3049 l
135.0283 403.3049 l
f*
155.0282 403.3049 m
155.0282 362.0772 l
154.5282 362.0772 l
154.5282 403.3049 l
f*
135.0283 457.0778 m
155.0282 457.0778 l
155.0282 456.5778 l
135.0283 456.5778 l
f*
155.0282 456.5778 m
155.0282 403.8049 l
154.5282 403.8049 l
154.5282 456.5778 l
f*
135.0283 499.7735 m
155.0282 499.7735 l
155.0282 499.2735 l
135.0283 499.2735 l
f*
155.0282 499.2735 m
155.0282 457.0778 l
154.5282 457.0778 l
154.5282 499.2735 l
f*
135.0283 544.2854 m
155.0282 544.2854 l
155.0282 543.7854 l
135.0283 543.7854 l
f*
155.0282 543.7854 m
155.0282 499.7735 l
154.5282 499.7735 l
154.5282 543.7854 l
f*
135.0283 634.0493 m
155.0282 634.0493 l
155.0282 633.5493 l
135.0283 633.5493 l
f*
155.0282 633.5493 m
155.0282 544.2854 l
154.5282 544.2854 l
154.5282 633.5493 l
f*
155.0282 713.2859 m
155.0282 634.0493 l
154.5282 634.0493 l
154.5282 713.2859 l
f*
155.0282 109.7212 m
183.528 109.7212 l
183.528 109.2212 l
155.0282 109.2212 l
f*
183.528 109.2212 m
183.528 83.2859 l
183.028 83.2859 l
183.028 109.2212 l
f*
155.0282 154.8479 m
183.528 154.8479 l
183.528 154.3479 l
155.0282 154.3479 l
f*
183.528 154.3479 m
183.528 109.7212 l
183.028 109.7212 l
183.028 154.3479 l
f*
155.0282 239.5772 m
183.528 239.5772 l
183.528 239.0771 l
155.0282 239.0771 l
f*
183.528 239.0771 m
183.528 154.8479 l
183.028 154.8479 l
183.028 239.0771 l
f*
155.0282 300.873 m
183.528 300.873 l
183.528 300.3729 l
155.0282 300.3729 l
f*
183.528 300.3729 m
183.528 239.5772 l
183.028 239.5772 l
183.028 300.3729 l
f*
155.0282 362.0772 m
183.528 362.0772 l
183.528 361.5772 l
155.0282 361.5772 l
f*
183.528 361.5772 m
183.528 300.873 l
183.028 300.873 l
183.028 361.5772 l
f*
155.0282 403.8049 m
183.528 403.8049 l
183.528 403.3049 l
155.0282 403.3049 l
f*
183.528 403.3049 m
183.528 362.0772 l
183.028 362.0772 l
183.028 403.3049 l
f*
155.0282 457.0778 m
183.528 457.0778 l
183.528 456.5778 l
155.0282 456.5778 l
f*
183.528 456.5778 m
183.528 403.8049 l
183.028 403.8049 l
183.028 456.5778 l
f*
155.0282 499.7735 m
183.528 499.7735 l
183.528 499.2735 l
155.0282 499.2735 l
f*
183.528 499.2735 m
183.528 457.0778 l
183.028 457.0778 l
183.028 499.2735 l
f*
155.0282 544.2854 m
183.528 544.2854 l
183.528 543.7854 l
155.0282 543.7854 l
f*
183.528 543.7854 m
183.528 499.7735 l
183.028 499.7735 l
183.028 543.7854 l
f*
155.0282 634.0493 m
183.528 634.0493 l
183.528 633.5493 l
155.0282 633.5493 l
f*
183.528 633.5493 m
183.528 544.2854 l
183.028 544.2854 l
183.028 633.5493 l
f*
183.528 713.2859 m
183.528 634.0493 l
183.028 634.0493 l
183.028 713.2859 l
f*
183.528 109.7212 m
203.5278 109.7212 l
203.5278 109.2212 l
183.528 109.2212 l
f*
203.5278 109.2212 m
203.5278 83.2859 l
203.0278 83.2859 l
203.0278 109.2212 l
f*
183.528 154.8479 m
203.5278 154.8479 l
203.5278 154.3479 l
183.528 154.3479 l
f*
203.5278 154.3479 m
203.5278 109.7212 l
203.0278 109.7212 l
203.0278 154.3479 l
f*
183.528 239.5772 m
203.5278 239.5772 l
203.5278 239.0771 l
183.528 239.0771 l
f*
203.5278 239.0771 m
203.5278 154.8479 l
203.0278 154.8479 l
203.0278 239.0771 l
f*
183.528 300.873 m
203.5278 300.873 l
203.5278 300.3729 l
183.528 300.3729 l
f*
203.5278 300.3729 m
203.5278 239.5772 l
203.0278 239.5772 l
203.0278 300.3729 l
f*
183.528 362.0772 m
203.5278 362.0772 l
203.5278 361.5772 l
183.528 361.5772 l
f*
203.5278 361.5772 m
203.5278 300.873 l
203.0278 300.873 l
203.0278 361.5772 l
f*
183.528 403.8049 m
203.5278 403.8049 l
203.5278 403.3049 l
183.528 403.3049 l
f*
203.5278 403.3049 m
203.5278 362.0772 l
203.0278 362.0772 l
203.0278 403.3049 l
f*
183.528 457.0778 m
203.5278 457.0778 l
203.5278 456.5778 l
183.528 456.5778 l
f*
203.5278 456.5778 m
203.5278 403.8049 l
203.0278 403.8049 l
203.0278 456.5778 l
f*
183.528 499.7735 m
203.5278 499.7735 l
203.5278 499.2735 l
183.528 499.2735 l
f*
203.5278 499.2735 m
203.5278 457.0778 l
203.0278 457.0778 l
203.0278 499.2735 l
f*
183.528 544.2854 m
203.5278 544.2854 l
203.5278 543.7854 l
183.528 543.7854 l
f*
203.5278 543.7854 m
203.5278 499.7735 l
203.0278 499.7735 l
203.0278 543.7854 l
f*
183.528 634.0493 m
203.5278 634.0493 l
203.5278 633.5493 l
183.528 633.5493 l
f*
203.5278 633.5493 m
203.5278 544.2854 l
203.0278 544.2854 l
203.0278 633.5493 l
f*
203.5278 713.2859 m
203.5278 634.0493 l
203.0278 634.0493 l
203.0278 713.2859 l
f*
203.5278 109.7212 m
223.5277 109.7212 l
223.5277 109.2212 l
203.5278 109.2212 l
f*
223.5277 109.2212 m
223.5277 83.2859 l
223.0277 83.2859 l
223.0277 109.2212 l
f*
203.5278 154.8479 m
223.5277 154.8479 l
223.5277 154.3479 l
203.5278 154.3479 l
f*
223.5277 154.3479 m
223.5277 109.7212 l
223.0277 109.7212 l
223.0277 154.3479 l
f*
203.5278 239.5772 m
223.5277 239.5772 l
223.5277 239.0771 l
203.5278 239.0771 l
f*
223.5277 239.0771 m
223.5277 154.8479 l
223.0277 154.8479 l
223.0277 239.0771 l
f*
203.5278 300.873 m
223.5277 300.873 l
223.5277 300.3729 l
203.5278 300.3729 l
f*
223.5277 300.3729 m
223.5277 239.5772 l
223.0277 239.5772 l
223.0277 300.3729 l
f*
203.5278 362.0772 m
223.5277 362.0772 l
223.5277 361.5772 l
203.5278 361.5772 l
f*
223.5277 361.5772 m
223.5277 300.873 l
223.0277 300.873 l
223.0277 361.5772 l
f*
203.5278 403.8049 m
223.5277 403.8049 l
223.5277 403.3049 l
203.5278 403.3049 l
f*
223.5277 403.3049 m
223.5277 362.0772 l
223.0277 362.0772 l
223.0277 403.3049 l
f*
203.5278 457.0778 m
223.5277 457.0778 l
223.5277 456.5778 l
203.5278 456.5778 l
f*
223.5277 456.5778 m
223.5277 403.8049 l
223.0277 403.8049 l
223.0277 456.5778 l
f*
203.5278 499.7735 m
223.5277 499.7735 l
223.5277 499.2735 l
203.5278 499.2735 l
f*
223.5277 499.2735 m
223.5277 457.0778 l
223.0277 457.0778 l
223.0277 499.2735 l
f*
203.5278 544.2854 m
223.5277 544.2854 l
223.5277 543.7854 l
203.5278 543.7854 l
f*
223.5277 543.7854 m
223.5277 499.7735 l
223.0277 499.7735 l
223.0277 543.7854 l
f*
203.5278 634.0493 m
223.5277 634.0493 l
223.5277 633.5493 l
203.5278 633.5493 l
f*
223.5277 633.5493 m
223.5277 544.2854 l
223.0277 544.2854 l
223.0277 633.5493 l
f*
223.5277 713.2859 m
223.5277 634.0493 l
223.0277 634.0493 l
223.0277 713.2859 l
f*
223.5277 109.7212 m
235.0276 109.7212 l
235.0276 109.2212 l
223.5277 109.2212 l
f*
235.0276 109.2212 m
235.0276 83.2859 l
234.5275 83.2859 l
234.5275 109.2212 l
f*
235.0276 713.2859 m
235.0276 109.7212 l
234.5275 109.7212 l
234.5275 713.2859 l
f*
235.0276 109.7212 m
272.0273 109.7212 l
272.0273 109.2212 l
235.0276 109.2212 l
f*
272.0273 109.2212 m
272.0273 83.2859 l
271.5273 83.2859 l
271.5273 109.2212 l
f*
235.0276 154.8479 m
272.0273 154.8479 l
272.0273 154.3479 l
235.0276 154.3479 l
f*
272.0273 154.3479 m
272.0273 109.7212 l
271.5273 109.7212 l
271.5273 154.3479 l
f*
235.0276 239.5772 m
272.0273 239.5772 l
272.0273 239.0771 l
235.0276 239.0771 l
f*
272.0273 239.0771 m
272.0273 154.8479 l
271.5273 154.8479 l
271.5273 239.0771 l
f*
235.0276 300.873 m
272.0273 300.873 l
272.0273 300.3729 l
235.0276 300.3729 l
f*
272.0273 300.3729 m
272.0273 239.5772 l
271.5273 239.5772 l
271.5273 300.3729 l
f*
235.0276 362.0772 m
272.0273 362.0772 l
272.0273 361.5772 l
235.0276 361.5772 l
f*
272.0273 361.5772 m
272.0273 300.873 l
271.5273 300.873 l
271.5273 361.5772 l
f*
235.0276 403.8049 m
272.0273 403.8049 l
272.0273 403.3049 l
235.0276 403.3049 l
f*
272.0273 403.3049 m
272.0273 362.0772 l
271.5273 362.0772 l
271.5273 403.3049 l
f*
235.0276 457.0778 m
272.0273 457.0778 l
272.0273 456.5778 l
235.0276 456.5778 l
f*
272.0273 456.5778 m
272.0273 403.8049 l
271.5273 403.8049 l
271.5273 456.5778 l
f*
235.0276 499.7735 m
272.0273 499.7735 l
272.0273 499.2735 l
235.0276 499.2735 l
f*
272.0273 499.2735 m
272.0273 457.0778 l
271.5273 457.0778 l
271.5273 499.2735 l
f*
235.0276 544.2854 m
272.0273 544.2854 l
272.0273 543.7854 l
235.0276 543.7854 l
f*
272.0273 543.7854 m
272.0273 499.7735 l
271.5273 499.7735 l
271.5273 543.7854 l
f*
235.0276 634.0493 m
272.0273 634.0493 l
272.0273 633.5493 l
235.0276 633.5493 l
f*
272.0273 633.5493 m
272.0273 544.2854 l
271.5273 544.2854 l
271.5273 633.5493 l
f*
272.0273 713.2859 m
272.0273 634.0493 l
271.5273 634.0493 l
271.5273 713.2859 l
f*
272.0273 109.7212 m
317.5271 109.7212 l
317.5271 109.2212 l
272.0273 109.2212 l
f*
317.5271 109.2212 m
317.5271 83.2859 l
317.0271 83.2859 l
317.0271 109.2212 l
f*
272.0273 154.8479 m
317.5271 154.8479 l
317.5271 154.3479 l
272.0273 154.3479 l
f*
317.5271 154.3479 m
317.5271 109.7212 l
317.0271 109.7212 l
317.0271 154.3479 l
f*
272.0273 239.5772 m
317.5271 239.5772 l
317.5271 239.0771 l
272.0273 239.0771 l
f*
317.5271 239.0771 m
317.5271 154.8479 l
317.0271 154.8479 l
317.0271 239.0771 l
f*
272.0273 300.873 m
317.5271 300.873 l
317.5271 300.3729 l
272.0273 300.3729 l
f*
317.5271 300.3729 m
317.5271 239.5772 l
317.0271 239.5772 l
317.0271 300.3729 l
f*
272.0273 362.0772 m
317.5271 362.0772 l
317.5271 361.5772 l
272.0273 361.5772 l
f*
317.5271 361.5772 m
317.5271 300.873 l
317.0271 300.873 l
317.0271 361.5772 l
f*
272.0273 403.8049 m
317.5271 403.8049 l
317.5271 403.3049 l
272.0273 403.3049 l
f*
317.5271 403.3049 m
317.5271 362.0772 l
317.0271 362.0772 l
317.0271 403.3049 l
f*
272.0273 457.0778 m
317.5271 457.0778 l
317.5271 456.5778 l
272.0273 456.5778 l
f*
317.5271 456.5778 m
317.5271 403.8049 l
317.0271 403.8049 l
317.0271 456.5778 l
f*
272.0273 499.7735 m
317.5271 499.7735 l
317.5271 499.2735 l
272.0273 499.2735 l
f*
317.5271 499.2735 m
317.5271 457.0778 l
317.0271 457.0778 l
317.0271 499.2735 l
f*
272.0273 544.2854 m
317.5271 544.2854 l
317.5271 543.7854 l
272.0273 543.7854 l
f*
317.5271 543.7854 m
317.5271 499.7735 l
317.0271 499.7735 l
317.0271 543.7854 l
f*
272.0273 634.0493 m
317.5271 634.0493 l
317.5271 633.5493 l
272.0273 633.5493 l
f*
317.5271 633.5493 m
317.5271 544.2854 l
317.0271 544.2854 l
317.0271 633.5493 l
f*
317.5271 713.2859 m
317.5271 634.0493 l
317.0271 634.0493 l
317.0271 713.2859 l
f*
317.5271 109.7212 m
354.5269 109.7212 l
354.5269 109.2212 l
317.5271 109.2212 l
f*
354.5269 109.2212 m
354.5269 83.2859 l
354.0268 83.2859 l
354.0268 109.2212 l
f*
317.5271 154.8479 m
354.5269 154.8479 l
354.5269 154.3479 l
317.5271 154.3479 l
f*
354.5269 154.3479 m
354.5269 109.7212 l
354.0268 109.7212 l
354.0268 154.3479 l
f*
317.5271 239.5772 m
354.5269 239.5772 l
354.5269 239.0771 l
317.5271 239.0771 l
f*
354.5269 239.0771 m
354.5269 154.8479 l
354.0268 154.8479 l
354.0268 239.0771 l
f*
317.5271 300.873 m
354.5269 300.873 l
354.5269 300.3729 l
317.5271 300.3729 l
f*
354.5269 300.3729 m
354.5269 239.5772 l
354.0268 239.5772 l
354.0268 300.3729 l
f*
317.5271 362.0772 m
354.5269 362.0772 l
354.5269 361.5772 l
317.5271 361.5772 l
f*
354.5269 361.5772 m
354.5269 300.873 l
354.0268 300.873 l
354.0268 361.5772 l
f*
317.5271 403.8049 m
354.5269 403.8049 l
354.5269 403.3049 l
317.5271 403.3049 l
f*
354.5269 403.3049 m
354.5269 362.0772 l
354.0268 362.0772 l
354.0268 403.3049 l
f*
317.5271 457.0778 m
354.5269 457.0778 l
354.5269 456.5778 l
317.5271 456.5778 l
f*
354.5269 456.5778 m
354.5269 403.8049 l
354.0268 403.8049 l
354.0268 456.5778 l
f*
317.5271 499.7735 m
354.5269 499.7735 l
354.5269 499.2735 l
317.5271 499.2735 l
f*
354.5269 499.2735 m
354.5269 457.0778 l
354.0268 457.0778 l
354.0268 499.2735 l
f*
317.5271 544.2854 m
354.5269 544.2854 l
354.5269 543.7854 l
317.5271 543.7854 l
f*
354.5269 543.7854 m
354.5269 499.7735 l
354.0268 499.7735 l
354.0268 543.7854 l
f*
317.5271 634.0493 m
354.5269 634.0493 l
354.5269 633.5493 l
317.5271 633.5493 l
f*
354.5269 633.5493 m
354.5269 544.2854 l
354.0268 544.2854 l
354.0268 633.5493 l
f*
354.5269 713.2859 m
354.5269 634.0493 l
354.0268 634.0493 l
354.0268 713.2859 l
f*
354.5269 109.7212 m
383.0267 109.7212 l
383.0267 109.2212 l
354.5269 109.2212 l
f*
383.0267 109.2212 m
383.0267 83.2859 l
382.5266 83.2859 l
382.5266 109.2212 l
f*
354.5269 154.8479 m
383.0267 154.8479 l
383.0267 154.3479 l
354.5269 154.3479 l
f*
383.0267 154.3479 m
383.0267 109.7212 l
382.5266 109.7212 l
382.5266 154.3479 l
f*
354.5269 239.5772 m
383.0267 239.5772 l
383.0267 239.0771 l
354.5269 239.0771 l
f*
383.0267 239.0771 m
383.0267 154.8479 l
382.5266 154.8479 l
382.5266 239.0771 l
f*
354.5269 300.873 m
383.0267 300.873 l
383.0267 300.3729 l
354.5269 300.3729 l
f*
383.0267 300.3729 m
383.0267 239.5772 l
382.5266 239.5772 l
382.5266 300.3729 l
f*
354.5269 362.0772 m
383.0267 362.0772 l
383.0267 361.5772 l
354.5269 361.5772 l
f*
383.0267 361.5772 m
383.0267 300.873 l
382.5266 300.873 l
382.5266 361.5772 l
f*
354.5269 403.8049 m
383.0267 403.8049 l
383.0267 403.3049 l
354.5269 403.3049 l
f*
383.0267 403.3049 m
383.0267 362.0772 l
382.5266 362.0772 l
382.5266 403.3049 l
f*
354.5269 457.0778 m
383.0267 457.0778 l
383.0267 456.5778 l
354.5269 456.5778 l
f*
383.0267 456.5778 m
383.0267 403.8049 l
382.5266 403.8049 l
382.5266 456.5778 l
f*
354.5269 499.7735 m
383.0267 499.7735 l
383.0267 499.2735 l
354.5269 499.2735 l
f*
383.0267 499.2735 m
383.0267 457.0778 l
382.5266 457.0778 l
382.5266 499.2735 l
f*
354.5269 544.2854 m
383.0267 544.2854 l
383.0267 543.7854 l
354.5269 543.7854 l
f*
383.0267 543.7854 m
383.0267 499.7735 l
382.5266 499.7735 l
382.5266 543.7854 l
f*
354.5269 634.0493 m
383.0267 634.0493 l
383.0267 633.5493 l
354.5269 633.5493 l
f*
383.0267 633.5493 m
383.0267 544.2854 l
382.5266 544.2854 l
382.5266 633.5493 l
f*
383.0267 713.2859 m
383.0267 634.0493 l
382.5266 634.0493 l
382.5266 713.2859 l
f*
383.0267 109.7212 m
411.5265 109.7212 l
411.5265 109.2212 l
383.0267 109.2212 l
f*
411.5265 109.2212 m
411.5265 83.2859 l
411.0265 83.2859 l
411.0265 109.2212 l
f*
383.0267 154.8479 m
411.5265 154.8479 l
411.5265 154.3479 l
383.0267 154.3479 l
f*
411.5265 154.3479 m
411.5265 109.7212 l
411.0265 109.7212 l
411.0265 154.3479 l
f*
383.0267 239.5772 m
411.5265 239.5772 l
411.5265 239.0771 l
383.0267 239.0771 l
f*
411.5265 239.0771 m
411.5265 154.8479 l
411.0265 154.8479 l
411.0265 239.0771 l
f*
383.0267 300.873 m
411.5265 300.873 l
411.5265 300.3729 l
383.0267 300.3729 l
f*
411.5265 300.3729 m
411.5265 239.5772 l
411.0265 239.5772 l
411.0265 300.3729 l
f*
383.0267 362.0772 m
411.5265 362.0772 l
411.5265 361.5772 l
383.0267 361.5772 l
f*
411.5265 361.5772 m
411.5265 300.873 l
411.0265 300.873 l
411.0265 361.5772 l
f*
383.0267 403.8049 m
411.5265 403.8049 l
411.5265 403.3049 l
383.0267 403.3049 l
f*
411.5265 403.3049 m
411.5265 362.0772 l
411.0265 362.0772 l
411.0265 403.3049 l
f*
383.0267 457.0778 m
411.5265 457.0778 l
411.5265 456.5778 l
383.0267 456.5778 l
f*
411.5265 456.5778 m
411.5265 403.8049 l
411.0265 403.8049 l
411.0265 456.5778 l
f*
383.0267 499.7735 m
411.5265 499.7735 l
411.5265 499.2735 l
383.0267 499.2735 l
f*
411.5265 499.2735 m
411.5265 457.0778 l
411.0265 457.0778 l
411.0265 499.2735 l
f*
383.0267 544.2854 m
411.5265 544.2854 l
411.5265 543.7854 l
383.0267 543.7854 l
f*
411.5265 543.7854 m
411.5265 499.7735 l
411.0265 499.7735 l
411.0265 543.7854 l
f*
383.0267 634.0493 m
411.5265 634.0493 l
411.5265 633.5493 l
383.0267 633.5493 l
f*
411.5265 633.5493 m
411.5265 544.2854 l
411.0265 544.2854 l
411.0265 633.5493 l
f*
411.5265 713.2859 m
411.5265 634.0493 l
411.0265 634.0493 l
411.0265 713.2859 l
f*
411.5265 109.7212 m
457.0262 109.7212 l
457.0262 109.2212 l
411.5265 109.2212 l
f*
457.0262 109.2212 m
457.0262 83.2859 l
456.5262 83.2859 l
456.5262 109.2212 l
f*
411.5265 154.8479 m
457.0262 154.8479 l
457.0262 154.3479 l
411.5265 154.3479 l
f*
457.0262 154.3479 m
457.0262 109.7212 l
456.5262 109.7212 l
456.5262 154.3479 l
f*
411.5265 239.5772 m
457.0262 239.5772 l
457.0262 239.0771 l
411.5265 239.0771 l
f*
457.0262 239.0771 m
457.0262 154.8479 l
456.5262 154.8479 l
456.5262 239.0771 l
f*
411.5265 300.873 m
457.0262 300.873 l
457.0262 300.3729 l
411.5265 300.3729 l
f*
457.0262 300.3729 m
457.0262 239.5772 l
456.5262 239.5772 l
456.5262 300.3729 l
f*
411.5265 362.0772 m
457.0262 362.0772 l
457.0262 361.5772 l
411.5265 361.5772 l
f*
457.0262 361.5772 m
457.0262 300.873 l
456.5262 300.873 l
456.5262 361.5772 l
f*
411.5265 403.8049 m
457.0262 403.8049 l
457.0262 403.3049 l
411.5265 403.3049 l
f*
457.0262 403.3049 m
457.0262 362.0772 l
456.5262 362.0772 l
456.5262 403.3049 l
f*
411.5265 457.0778 m
457.0262 457.0778 l
457.0262 456.5778 l
411.5265 456.5778 l
f*
457.0262 456.5778 m
457.0262 403.8049 l
456.5262 403.8049 l
456.5262 456.5778 l
f*
411.5265 499.7735 m
457.0262 499.7735 l
457.0262 499.2735 l
411.5265 499.2735 l
f*
457.0262 499.2735 m
457.0262 457.0778 l
456.5262 457.0778 l
456.5262 499.2735 l
f*
411.5265 544.2854 m
457.0262 544.2854 l
457.0262 543.7854 l
411.5265 543.7854 l
f*
457.0262 543.7854 m
457.0262 499.7735 l
456.5262 499.7735 l
456.5262 543.7854 l
f*
411.5265 634.0493 m
457.0262 634.0493 l
457.0262 633.5493 l
411.5265 633.5493 l
f*
457.0262 633.5493 m
457.0262 544.2854 l
456.5262 544.2854 l
456.5262 633.5493 l
f*
457.0262 713.2859 m
457.0262 634.0493 l
456.5262 634.0493 l
456.5262 713.2859 l
f*
457.0262 109.7212 m
494.026 109.7212 l
494.026 109.2212 l
457.0262 109.2212 l
f*
494.026 109.2212 m
494.026 83.2859 l
493.526 83.2859 l
493.526 109.2212 l
f*
457.0262 154.8479 m
494.026 154.8479 l
494.026 154.3479 l
457.0262 154.3479 l
f*
494.026 154.3479 m
494.026 109.7212 l
493.526 109.7212 l
493.526 154.3479 l
f*
457.0262 239.5772 m
494.026 239.5772 l
494.026 239.0771 l
457.0262 239.0771 l
f*
494.026 239.0771 m
494.026 154.8479 l
493.526 154.8479 l
493.526 239.0771 l
f*
457.0262 300.873 m
494.026 300.873 l
494.026 300.3729 l
457.0262 300.3729 l
f*
494.026 300.3729 m
494.026 239.5772 l
493.526 239.5772 l
493.526 300.3729 l
f*
457.0262 362.0772 m
494.026 362.0772 l
494.026 361.5772 l
457.0262 361.5772 l
f*
494.026 361.5772 m
494.026 300.873 l
493.526 300.873 l
493.526 361.5772 l
f*
457.0262 403.8049 m
494.026 403.8049 l
494.026 403.3049 l
457.0262 403.3049 l
f*
494.026 403.3049 m
494.026 362.0772 l
493.526 362.0772 l
493.526 403.3049 l
f*
457.0262 457.0778 m
494.026 457.0778 l
494.026 456.5778 l
457.0262 456.5778 l
f*
494.026 456.5778 m
494.026 403.8049 l
493.526 403.8049 l
493.526 456.5778 l
f*
457.0262 499.7735 m
494.026 499.7735 l
494.026 499.2735 l
457.0262 499.2735 l
f*
494.026 499.2735 m
494.026 457.0778 l
493.526 457.0778 l
493.526 499.2735 l
f*
457.0262 544.2854 m
494.026 544.2854 l
494.026 543.7854 l
457.0262 543.7854 l
f*
494.026 543.7854 m
494.026 499.7735 l
493.526 499.7735 l
493.526 543.7854 l
f*
457.0262 634.0493 m
494.026 634.0493 l
494.026 633.5493 l
457.0262 633.5493 l
f*
494.026 633.5493 m
494.026 544.2854 l
493.526 544.2854 l
493.526 633.5493 l
f*
494.026 713.2859 m
494.026 634.0493 l
493.526 634.0493 l
493.526 713.2859 l
f*
494.026 109.7212 m
531.0258 109.7212 l
531.0258 109.2212 l
494.026 109.2212 l
f*
531.0258 109.2212 m
531.0258 83.2859 l
530.5258 83.2859 l
530.5258 109.2212 l
f*
494.026 154.8479 m
531.0258 154.8479 l
531.0258 154.3479 l
494.026 154.3479 l
f*
531.0258 154.3479 m
531.0258 109.7212 l
530.5258 109.7212 l
530.5258 154.3479 l
f*
494.026 239.5772 m
531.0258 239.5772 l
531.0258 239.0771 l
494.026 239.0771 l
f*
531.0258 239.0771 m
531.0258 154.8479 l
530.5258 154.8479 l
530.5258 239.0771 l
f*
494.026 300.873 m
531.0258 300.873 l
531.0258 300.3729 l
494.026 300.3729 l
f*
531.0258 300.3729 m
531.0258 239.5772 l
530.5258 239.5772 l
530.5258 300.3729 l
f*
494.026 362.0772 m
531.0258 362.0772 l
531.0258 361.5772 l
494.026 361.5772 l
f*
531.0258 361.5772 m
531.0258 300.873 l
530.5258 300.873 l
530.5258 361.5772 l
f*
494.026 403.8049 m
531.0258 403.8049 l
531.0258 403.3049 l
494.026 403.3049 l
f*
531.0258 403.3049 m
531.0258 362.0772 l
530.5258 362.0772 l
530.5258 403.3049 l
f*
494.026 457.0778 m
531.0258 457.0778 l
531.0258 456.5778 l
494.026 456.5778 l
f*
531.0258 456.5778 m
531.0258 403.8049 l
530.5258 403.8049 l
530.5258 456.5778 l
f*
494.026 499.7735 m
531.0258 499.7735 l
531.0258 499.2735 l
494.026 499.2735 l
f*
531.0258 499.2735 m
531.0258 457.0778 l
530.5258 457.0778 l
530.5258 499.2735 l
f*
494.026 544.2854 m
531.0258 544.2854 l
531.0258 543.7854 l
494.026 543.7854 l
f*
531.0258 543.7854 m
531.0258 499.7735 l
530.5258 499.7735 l
530.5258 543.7854 l
f*
494.026 634.0493 m
531.0258 634.0493 l
531.0258 633.5493 l
494.026 633.5493 l
f*
531.0258 633.5493 m
531.0258 544.2854 l
530.5258 544.2854 l
530.5258 633.5493 l
f*
531.0258 713.2859 m
531.0258 634.0493 l
530.5258 634.0493 l
530.5258 713.2859 l
f*
531.0258 83.2859 m
531.0258 713.2859 l
531.5258 713.2859 l
531.5258 83.2859 l
f*
0.83 0.64 0.02 0 k
244.6299 516.8126 m
244.6299 524.5228 l
h
f*
327.1181 516.8126 m
327.1181 524.5228 l
h
f*
421.115 516.8126 m
421.115 524.5228 l
h
f*
0 g
1 j
1 J
0 7.9999 -7.9999 0 40.7055 83.2818 cm
BT
/F3 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.7992 0 Td
(2.)Tj
1.2614 0 Td
(Genetic)Tj
3.841 0 Td
(variants)Tj
3.9898 0 Td
(identified)Tj
4.6134 0 Td
(in)Tj
1.1055 0 Td
(candidate)Tj
4.826 0 Td
(genes)Tj
3.0757 0 Td
(in)Tj
1.0984 0 Td
(study)Tj
2.8559 0 Td
(subjects)Tj
3.9969 0 Td
(.)Tj
ET
Q
q
1 j
1 J
0 w
0 6.9998 -6.9998 0 58.0535 83.2818 cm
BT
/F3 1 Tf
1 TL
0 0 Td
(Gene)Tj
4.0657 0 Td
(Genomic)Tj
0 -1.2067 Td
(coordinate)Tj
6.4469 1.2067 Td
(Nucleotide)Tj
5.3536 0 Td
(change)Tj
6.7465 0 Td
(Mutation)Tj
4.4141 0 Td
(type)Tj
4.3411 0 Td
(Amino)Tj
3.353 0 Td
(acid)Tj
-3.353 -1.2067 Td
(change)Tj
3.7418 0 Td
(\(rs)Tj
-3.7418 -1.2149 Td
(number)Tj
3.9038 0 Td
(in)Tj
-3.9038 -1.2149 Td
(dbSNP\))Tj
8.7471 3.6365 Td
(Allele)Tj
0 -1.2067 Td
(frequency)Tj
5.9609 1.2067 Td
(Frequency)Tj
5.2888 0 Td
(in)Tj
-5.2888 -1.2067 Td
(gnomAD)Tj
0 -1.2149 Td
(Database)Tj
0 -1.2149 Td
(\(East)Tj
2.6727 0 Td
(Asian\))Tj
4.9405 3.6365 Td
(Affected)Tj
0 -1.2067 Td
(patients)Tj
0 -1.2149 Td
(\(homo/)Tj
0 -1.2149 Td
(hetero\))Tj
6.0987 3.6365 Td
(Report)Tj
6.3578 0 Td
(Effect)Tj
12.8209 0 Td
(SIFT/Polyphen/)Tj
0 -1.2067 Td
(Mutation)Tj
4.414 0 Td
(taster)Tj
-4.414 -1.2149 Td
(prediction)Tj
5.0863 0 Td
(\(Clinical)Tj
-5.0863 -1.2149 Td
(significance)Tj
6.0258 0 Td
(based)Tj
3.1181 0 Td
(on)Tj
-9.1439 -1.2148 Td
(clinVar\))Tj
/F6 1 Tf
-78.9665 -1.6442 Td
(APOB)Tj
/F0 1 Tf
43.9458 0 Td
(Rare)Tj
2.3893 0 Td
(variants)Tj
-42.1317 -1.6441 Td
(chr2:)Tj
0 -1.2148 Td
(21,227,212)Tj
6.4469 1.2148 Td
(c.G12016A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.V4006I)Tj
0 -1.2148 Td
(\(rs183117027\))Tj
8.747 1.2148 Td
(0.045)Tj
5.961 0 Td
(0.006)Tj
7.6051 0 Td
(0/2)Tj
6.0986 0 Td
(Yes)Tj
/F5 1 Tf
[()]TJ
/F0 1 Tf
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/)Tj
4.7299 0 Td
(benign/)Tj
-4.7299 -1.2148 Td
(disease_causing)Tj
0 -1.2149 Td
(\(Likely)Tj
3.1101 0 Td
(benign\))Tj
-78.019 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,228,620)Tj
6.4469 1.2149 Td
(c.C11120T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.A3707V)Tj
0 -1.2149 Td
(\(rs756381590\))Tj
8.747 1.2149 Td
(0.023)Tj
/F9 1 Tf
5.961 0 Td
[( )]TJ
/F0 1 Tf
(0.001)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(Polymorphism)Tj
6.5522 0 Td
(\(NA\))Tj
-81.4611 -1.636 Td
(chr2:)Tj
0 -1.2149 Td
(21,247,843)Tj
6.4469 1.2149 Td
(c.C2398A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.L800M)Tj
0 -1.2149 Td
(\(rs183950016\))Tj
8.747 1.2149 Td
(0.045)Tj
/F9 1 Tf
5.961 0 Td
[( )]TJ
/F0 1 Tf
(0.001)Tj
7.6051 0 Td
(0/2)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/)Tj
4.7299 0 Td
(possibly)Tj
-4.7299 -1.2149 Td
(damaging/)Tj
0 -1.2149 Td
(disease_causing)Tj
7.6456 0 Td
(\(NA\))Tj
-82.5545 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,255,236)Tj
6.4469 1.2149 Td
(c.G1342A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.A448T)Tj
0 -1.2149 Td
(\(rs752032737\))Tj
8.747 1.2149 Td
(0.023)Tj
/F9 1 Tf
5.961 0 Td
[( )]TJ
/F0 1 Tf
(0.001)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(polymorphism)Tj
6.4388 0 Td
(\(NA\))Tj
-81.3477 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,266,783)Tj
6.4469 1.2149 Td
(c.T35C)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.L12P)Tj
0 -1.2149 Td
(\(rs758450840\))Tj
8.747 1.2149 Td
(0.068)Tj
/F9 1 Tf
5.961 0 Td
[( )]TJ
/F0 1 Tf
(0.001)Tj
7.6051 0 Td
(0/3)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Deleterious/)Tj
5.5479 0 Td
(benign/)Tj
-5.5479 -1.2149 Td
(polymorphism)Tj
6.4388 0 Td
(\(NA\))Tj
-42.5448 -1.6441 Td
(Common)Tj
4.2764 0 Td
(variants)Tj
-43.0793 -1.6441 Td
(chr2:)Tj
0 -1.2068 Td
(21,225,281)Tj
6.4469 1.2068 Td
(c.G13013A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2068 Td
(SNV)Tj
8.7552 1.2068 Td
(p.S4338N)Tj
0 -1.2068 Td
(\(rs1042034\))Tj
8.747 1.2068 Td
(0.273)Tj
5.961 0 Td
(0.273)Tj
7.6051 0 Td
(1/10)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/benign/)Tj
0 -1.2068 Td
(polymorphism_)Tj
0 -1.2149 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2148 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-77.6869 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,231,387)Tj
6.4469 1.2149 Td
(c.A8353C)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.N2785H)Tj
0 -1.2149 Td
(\(rs2163204\))Tj
8.747 1.2149 Td
(0.045)Tj
5.961 0 Td
(0.059)Tj
7.6051 0 Td
(0/2)Tj
6.0986 0 Td
(Yes)Tj
/F5 1 Tf
[()]TJ
/F0 1 Tf
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(polymorphism)Tj
0 -1.2149 Td
(\(Conflicting)Tj
0 -1.2149 Td
(interpretations)Tj
6.5522 0 Td
(of)Tj
-6.5522 -1.2148 Td
(pathogenicity\))Tj
-74.9089 -1.6442 Td
(chr2:)Tj
0 -1.2148 Td
(21,231,524)Tj
6.4469 1.2148 Td
(c.C8216T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.P2739L)Tj
0 -1.2148 Td
(\(rs676210\))Tj
8.747 1.2148 Td
(0.364)Tj
5.961 0 Td
(0.725)Tj
7.6051 0 Td
(3/10)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
6.366 0 Td
(Familial)Tj
0 -1.2148 Td
(hypercholesterolemia;)Tj
0 -1.2149 Td
(hypocholesterolemia)Tj
12.8209 2.4297 Td
(Deleterious/probab)Tj
8.4231 0 Td
(ly)Tj
-8.4231 -1.2148 Td
(damaging/)Tj
4.8838 0 Td
(Possibly)Tj
-4.8838 -1.2149 Td
(damaging)Tj
4.6003 0 Td
(\(Benign/)Tj
-4.6003 -1.2149 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-77.6869 -1.636 Td
(chr2:)Tj
0 -1.2149 Td
(21,232,803)Tj
6.4469 1.2149 Td
(c.A6937G)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.I2313V)Tj
0 -1.2149 Td
(\(rs584542\))Tj
8.747 1.2149 Td
(0.455)Tj
5.961 0 Td
(0.999)Tj
7.6051 0 Td
(10/0)Tj
6.0986 0 Td
(Yes)Tj
/F5 1 Tf
[()]TJ
/F0 1 Tf
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(Possibly)Tj
3.9443 0 Td
(damaging)Tj
-3.9443 -1.2148 Td
(\(Benign\))Tj
-74.9089 -1.6442 Td
(chr2:)Tj
0 -1.2148 Td
(21,235,475)Tj
6.4469 1.2148 Td
(c.A4265G)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.Y1422C)Tj
0 -1.2148 Td
(\(rs568413\))Tj
8.747 1.2148 Td
(0.545)Tj
5.961 0 Td
(1.000)Tj
7.6051 0 Td
(12/0)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2148 Td
(Possibly)Tj
3.9443 0 Td
(damaging)Tj
-3.9443 -1.2149 Td
(\(NA\))Tj
-74.9089 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,250,914)Tj
6.4469 1.2149 Td
(c.C1853T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.A618V)Tj
0 -1.2149 Td
(\(rs679899\))Tj
8.747 1.2149 Td
(0.545)Tj
5.961 0 Td
(0.851)Tj
7.6051 0 Td
(11/2)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
6.366 0 Td
(Hypocholesterolemia)Tj
12.8209 0 Td
(Tolerated/probably)Tj
0 -1.2149 Td
(damaging/)Tj
0 -1.2149 Td
(Polymorphism_)Tj
0 -1.2148 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2149 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-77.6869 -1.636 Td
(chr2:)Tj
0 -1.2149 Td
(21,252,534)Tj
6.4469 1.2149 Td
(c.C1594T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.R532W)Tj
4.3897 0 Td
(or)Tj
-4.3897 -1.2149 Td
(R505W)Tj
0 -1.2149 Td
(\(rs13306194\))Tj
8.747 2.4298 Td
(0.159)Tj
5.961 0 Td
(0.135)Tj
7.6051 0 Td
(0/6)Tj
6.0986 0 Td
(Yes\(Yilmaz\))Tj
6.366 0 Td
(Familial)Tj
0 -1.2149 Td
(hypobetalipoproteinemia)Tj
12.8209 1.2149 Td
(Deleterious/probab)Tj
8.4231 0 Td
(ly)Tj
-8.4231 -1.2149 Td
(damaging/)Tj
0 -1.2149 Td
(Disease_causing)Tj
0 -1.2148 Td
(\(Likely)Tj
3.1101 0 Td
(benign\))Tj
-78.019 -1.6442 Td
(chr2:)Tj
0 -1.2148 Td
(21,260,084)Tj
6.4469 1.2148 Td
(c.C581T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.T194M)Tj
0 -1.2148 Td
(\(rs13306198\))Tj
8.747 1.2148 Td
(0.045)Tj
5.961 0 Td
(0.055)Tj
7.6051 0 Td
(0/2)Tj
6.0986 0 Td
(Yes)Tj
/F5 1 Tf
[()]TJ
/F0 1 Tf
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Deleterious/probab)Tj
8.4231 0 Td
(ly)Tj
-8.4231 -1.2148 Td
(damaging/)Tj
0 -1.2149 Td
(polymorphism)Tj
6.4388 0 Td
(\(Likely)Tj
-6.4388 -1.2149 Td
(benign\))Tj
ET
Q
q
1 j
1 J
0 w
0 7.9999 -7.9999 0 541.5307 671.0173 cm
BT
/F0 1 Tf
1 TL
0 0 Td
(\()Tj
/F6 1 Tf
(Continued)Tj
/F0 1 Tf
4.9535 0 Td
(\))Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 437.8393 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Genetic)Tj
3.6142 0 Td
(variants)Tj
3.6567 0 Td
(in)Tj
0.9779 0 Td
(extremely)Tj
4.4859 0 Td
(low)Tj
1.6866 0 Td
(LDL-C)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01864)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(16,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(5)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
103 0 obj
<>stream
endstream
endobj
104 0 obj
<>stream
BT
66.402 0 Td
(13)Tj
ET
Q
endstream
endobj
105 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 106 0 R/Contents 107 0 R/TrimBox[0 0 612 792]>>
endobj
106 0 obj
[108 0 R 109 0 R 110 0 R 111 0 R 112 0 R 113 0 R 114 0 R 115 0 R 116 0 R 117 0 R 118 0 R 119 0 R 120 0 R 121 0 R]
endobj
108 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref011)>>
endobj
109 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref006)>>
endobj
110 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref012)>>
endobj
111 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref012)>>
endobj
112 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref013)>>
endobj
113 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref013)>>
endobj
114 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref006)>>
endobj
115 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref014)>>
endobj
116 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref006)>>
endobj
117 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref012)>>
endobj
118 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref013)>>
endobj
119 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186446.ref015)>>
endobj
120 0 obj
<>/Border[0 0 0]/A 122 0 R>>
endobj
122 0 obj
<>
endobj
121 0 obj
<>/Border[0 0 0]/A 123 0 R>>
endobj
123 0 obj
<>
endobj
107 0 obj
[124 0 R 125 0 R 126 0 R 127 0 R 128 0 R 129 0 R 130 0 R]
endobj
124 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
48.4183 83.2859 m
48.4183 713.2859 l
48.9183 713.2859 l
48.9183 83.2859 l
f*
48.9183 109.7212 m
94.4181 109.7212 l
94.4181 109.2212 l
48.9183 109.2212 l
f*
94.4181 109.2212 m
94.4181 83.2859 l
93.918 83.2859 l
93.918 109.2212 l
f*
48.9183 154.8479 m
94.4181 154.8479 l
94.4181 154.3479 l
48.9183 154.3479 l
f*
94.4181 154.3479 m
94.4181 109.7212 l
93.918 109.7212 l
93.918 154.3479 l
f*
48.9183 239.5772 m
94.4181 239.5772 l
94.4181 239.0771 l
48.9183 239.0771 l
f*
94.4181 239.0771 m
94.4181 154.8479 l
93.918 154.8479 l
93.918 239.0771 l
f*
48.9183 300.873 m
94.4181 300.873 l
94.4181 300.3729 l
48.9183 300.3729 l
f*
94.4181 300.3729 m
94.4181 239.5772 l
93.918 239.5772 l
93.918 300.3729 l
f*
48.9183 362.0772 m
94.4181 362.0772 l
94.4181 361.5772 l
48.9183 361.5772 l
f*
94.4181 361.5772 m
94.4181 300.873 l
93.918 300.873 l
93.918 361.5772 l
f*
48.9183 403.8049 m
94.4181 403.8049 l
94.4181 403.3049 l
48.9183 403.3049 l
f*
94.4181 403.3049 m
94.4181 362.0772 l
93.918 362.0772 l
93.918 403.3049 l
f*
48.9183 457.0778 m
94.4181 457.0778 l
94.4181 456.5778 l
48.9183 456.5778 l
f*
94.4181 456.5778 m
94.4181 403.8049 l
93.918 403.8049 l
93.918 456.5778 l
f*
48.9183 499.7735 m
94.4181 499.7735 l
94.4181 499.2735 l
48.9183 499.2735 l
f*
94.4181 499.2735 m
94.4181 457.0778 l
93.918 457.0778 l
93.918 499.2735 l
f*
48.9183 544.2854 m
94.4181 544.2854 l
94.4181 543.7854 l
48.9183 543.7854 l
f*
94.4181 543.7854 m
94.4181 499.7735 l
93.918 499.7735 l
93.918 543.7854 l
f*
48.9183 634.0493 m
94.4181 634.0493 l
94.4181 633.5493 l
48.9183 633.5493 l
f*
94.4181 633.5493 m
94.4181 544.2854 l
93.918 544.2854 l
93.918 633.5493 l
f*
94.4181 713.2859 m
94.4181 634.0493 l
93.918 634.0493 l
93.918 713.2859 l
f*
94.4181 109.7212 m
131.4179 109.7212 l
131.4179 109.2212 l
94.4181 109.2212 l
f*
131.4179 109.2212 m
131.4179 83.2859 l
130.9178 83.2859 l
130.9178 109.2212 l
f*
94.4181 154.8479 m
131.4179 154.8479 l
131.4179 154.3479 l
94.4181 154.3479 l
f*
131.4179 154.3479 m
131.4179 109.7212 l
130.9178 109.7212 l
130.9178 154.3479 l
f*
94.4181 239.5772 m
131.4179 239.5772 l
131.4179 239.0771 l
94.4181 239.0771 l
f*
131.4179 239.0771 m
131.4179 154.8479 l
130.9178 154.8479 l
130.9178 239.0771 l
f*
94.4181 300.873 m
131.4179 300.873 l
131.4179 300.3729 l
94.4181 300.3729 l
f*
131.4179 300.3729 m
131.4179 239.5772 l
130.9178 239.5772 l
130.9178 300.3729 l
f*
94.4181 362.0772 m
131.4179 362.0772 l
131.4179 361.5772 l
94.4181 361.5772 l
f*
131.4179 361.5772 m
131.4179 300.873 l
130.9178 300.873 l
130.9178 361.5772 l
f*
94.4181 403.8049 m
131.4179 403.8049 l
131.4179 403.3049 l
94.4181 403.3049 l
f*
131.4179 403.3049 m
131.4179 362.0772 l
130.9178 362.0772 l
130.9178 403.3049 l
f*
94.4181 457.0778 m
131.4179 457.0778 l
131.4179 456.5778 l
94.4181 456.5778 l
f*
131.4179 456.5778 m
131.4179 403.8049 l
130.9178 403.8049 l
130.9178 456.5778 l
f*
94.4181 499.7735 m
131.4179 499.7735 l
131.4179 499.2735 l
94.4181 499.2735 l
f*
131.4179 499.2735 m
131.4179 457.0778 l
130.9178 457.0778 l
130.9178 499.2735 l
f*
94.4181 544.2854 m
131.4179 544.2854 l
131.4179 543.7854 l
94.4181 543.7854 l
f*
131.4179 543.7854 m
131.4179 499.7735 l
130.9178 499.7735 l
130.9178 543.7854 l
f*
94.4181 634.0493 m
131.4179 634.0493 l
131.4179 633.5493 l
94.4181 633.5493 l
f*
131.4179 633.5493 m
131.4179 544.2854 l
130.9178 544.2854 l
130.9178 633.5493 l
f*
131.4179 713.2859 m
131.4179 634.0493 l
130.9178 634.0493 l
130.9178 713.2859 l
f*
131.4179 109.7212 m
142.9177 109.7212 l
142.9177 109.2212 l
131.4179 109.2212 l
f*
142.9177 109.2212 m
142.9177 83.2859 l
142.4177 83.2859 l
142.4177 109.2212 l
f*
142.9177 713.2859 m
142.9177 109.7212 l
142.4177 109.7212 l
142.4177 713.2859 l
f*
142.9177 109.7212 m
162.9176 109.7212 l
162.9176 109.2212 l
142.9177 109.2212 l
f*
162.9176 109.2212 m
162.9176 83.2859 l
162.4175 83.2859 l
162.4175 109.2212 l
f*
142.9177 154.8479 m
162.9176 154.8479 l
162.9176 154.3479 l
142.9177 154.3479 l
f*
162.9176 154.3479 m
162.9176 109.7212 l
162.4175 109.7212 l
162.4175 154.3479 l
f*
142.9177 239.5772 m
162.9176 239.5772 l
162.9176 239.0771 l
142.9177 239.0771 l
f*
162.9176 239.0771 m
162.9176 154.8479 l
162.4175 154.8479 l
162.4175 239.0771 l
f*
142.9177 300.873 m
162.9176 300.873 l
162.9176 300.3729 l
142.9177 300.3729 l
f*
162.9176 300.3729 m
162.9176 239.5772 l
162.4175 239.5772 l
162.4175 300.3729 l
f*
142.9177 362.0772 m
162.9176 362.0772 l
162.9176 361.5772 l
142.9177 361.5772 l
f*
162.9176 361.5772 m
162.9176 300.873 l
162.4175 300.873 l
162.4175 361.5772 l
f*
142.9177 403.8049 m
162.9176 403.8049 l
162.9176 403.3049 l
142.9177 403.3049 l
f*
162.9176 403.3049 m
162.9176 362.0772 l
162.4175 362.0772 l
162.4175 403.3049 l
f*
142.9177 457.0778 m
162.9176 457.0778 l
162.9176 456.5778 l
142.9177 456.5778 l
f*
162.9176 456.5778 m
162.9176 403.8049 l
162.4175 403.8049 l
162.4175 456.5778 l
f*
142.9177 499.7735 m
162.9176 499.7735 l
162.9176 499.2735 l
142.9177 499.2735 l
f*
162.9176 499.2735 m
162.9176 457.0778 l
162.4175 457.0778 l
162.4175 499.2735 l
f*
142.9177 544.2854 m
162.9176 544.2854 l
162.9176 543.7854 l
142.9177 543.7854 l
f*
162.9176 543.7854 m
162.9176 499.7735 l
162.4175 499.7735 l
162.4175 543.7854 l
f*
142.9177 634.0493 m
162.9176 634.0493 l
162.9176 633.5493 l
142.9177 633.5493 l
f*
162.9176 633.5493 m
162.9176 544.2854 l
162.4175 544.2854 l
162.4175 633.5493 l
f*
162.9176 713.2859 m
162.9176 634.0493 l
162.4175 634.0493 l
162.4175 713.2859 l
f*
162.9176 109.7212 m
174.4174 109.7212 l
174.4174 109.2212 l
162.9176 109.2212 l
f*
174.4174 109.2212 m
174.4174 83.2859 l
173.9174 83.2859 l
173.9174 109.2212 l
f*
174.4174 713.2859 m
174.4174 109.7212 l
173.9174 109.7212 l
173.9174 713.2859 l
f*
174.4174 109.7212 m
194.4173 109.7212 l
194.4173 109.2212 l
174.4174 109.2212 l
f*
194.4173 109.2212 m
194.4173 83.2859 l
193.9173 83.2859 l
193.9173 109.2212 l
f*
174.4174 154.8479 m
194.4173 154.8479 l
194.4173 154.3479 l
174.4174 154.3479 l
f*
194.4173 154.3479 m
194.4173 109.7212 l
193.9173 109.7212 l
193.9173 154.3479 l
f*
174.4174 239.5772 m
194.4173 239.5772 l
194.4173 239.0771 l
174.4174 239.0771 l
f*
194.4173 239.0771 m
194.4173 154.8479 l
193.9173 154.8479 l
193.9173 239.0771 l
f*
174.4174 300.873 m
194.4173 300.873 l
194.4173 300.3729 l
174.4174 300.3729 l
f*
194.4173 300.3729 m
194.4173 239.5772 l
193.9173 239.5772 l
193.9173 300.3729 l
f*
174.4174 362.0772 m
194.4173 362.0772 l
194.4173 361.5772 l
174.4174 361.5772 l
f*
194.4173 361.5772 m
194.4173 300.873 l
193.9173 300.873 l
193.9173 361.5772 l
f*
174.4174 403.8049 m
194.4173 403.8049 l
194.4173 403.3049 l
174.4174 403.3049 l
f*
194.4173 403.3049 m
194.4173 362.0772 l
193.9173 362.0772 l
193.9173 403.3049 l
f*
174.4174 457.0778 m
194.4173 457.0778 l
194.4173 456.5778 l
174.4174 456.5778 l
f*
194.4173 456.5778 m
194.4173 403.8049 l
193.9173 403.8049 l
193.9173 456.5778 l
f*
174.4174 499.7735 m
194.4173 499.7735 l
194.4173 499.2735 l
174.4174 499.2735 l
f*
194.4173 499.2735 m
194.4173 457.0778 l
193.9173 457.0778 l
193.9173 499.2735 l
f*
174.4174 544.2854 m
194.4173 544.2854 l
194.4173 543.7854 l
174.4174 543.7854 l
f*
194.4173 543.7854 m
194.4173 499.7735 l
193.9173 499.7735 l
193.9173 543.7854 l
f*
174.4174 634.0493 m
194.4173 634.0493 l
194.4173 633.5493 l
174.4174 633.5493 l
f*
194.4173 633.5493 m
194.4173 544.2854 l
193.9173 544.2854 l
193.9173 633.5493 l
f*
194.4173 713.2859 m
194.4173 634.0493 l
193.9173 634.0493 l
193.9173 713.2859 l
f*
194.4173 109.7212 m
222.9171 109.7212 l
222.9171 109.2212 l
194.4173 109.2212 l
f*
222.9171 109.2212 m
222.9171 83.2859 l
222.4171 83.2859 l
222.4171 109.2212 l
f*
194.4173 154.8479 m
222.9171 154.8479 l
222.9171 154.3479 l
194.4173 154.3479 l
f*
222.9171 154.3479 m
222.9171 109.7212 l
222.4171 109.7212 l
222.4171 154.3479 l
f*
194.4173 239.5772 m
222.9171 239.5772 l
222.9171 239.0771 l
194.4173 239.0771 l
f*
222.9171 239.0771 m
222.9171 154.8479 l
222.4171 154.8479 l
222.4171 239.0771 l
f*
194.4173 300.873 m
222.9171 300.873 l
222.9171 300.3729 l
194.4173 300.3729 l
f*
222.9171 300.3729 m
222.9171 239.5772 l
222.4171 239.5772 l
222.4171 300.3729 l
f*
194.4173 362.0772 m
222.9171 362.0772 l
222.9171 361.5772 l
194.4173 361.5772 l
f*
222.9171 361.5772 m
222.9171 300.873 l
222.4171 300.873 l
222.4171 361.5772 l
f*
194.4173 403.8049 m
222.9171 403.8049 l
222.9171 403.3049 l
194.4173 403.3049 l
f*
222.9171 403.3049 m
222.9171 362.0772 l
222.4171 362.0772 l
222.4171 403.3049 l
f*
194.4173 457.0778 m
222.9171 457.0778 l
222.9171 456.5778 l
194.4173 456.5778 l
f*
222.9171 456.5778 m
222.9171 403.8049 l
222.4171 403.8049 l
222.4171 456.5778 l
f*
194.4173 499.7735 m
222.9171 499.7735 l
222.9171 499.2735 l
194.4173 499.2735 l
f*
222.9171 499.2735 m
222.9171 457.0778 l
222.4171 457.0778 l
222.4171 499.2735 l
f*
194.4173 544.2854 m
222.9171 544.2854 l
222.9171 543.7854 l
194.4173 543.7854 l
f*
222.9171 543.7854 m
222.9171 499.7735 l
222.4171 499.7735 l
222.4171 543.7854 l
f*
194.4173 634.0493 m
222.9171 634.0493 l
222.9171 633.5493 l
194.4173 633.5493 l
f*
222.9171 633.5493 m
222.9171 544.2854 l
222.4171 544.2854 l
222.4171 633.5493 l
f*
222.9171 713.2859 m
222.9171 634.0493 l
222.4171 634.0493 l
222.4171 713.2859 l
f*
222.9171 109.7212 m
251.4169 109.7212 l
251.4169 109.2212 l
222.9171 109.2212 l
f*
251.4169 109.2212 m
251.4169 83.2859 l
250.9169 83.2859 l
250.9169 109.2212 l
f*
222.9171 154.8479 m
251.4169 154.8479 l
251.4169 154.3479 l
222.9171 154.3479 l
f*
251.4169 154.3479 m
251.4169 109.7212 l
250.9169 109.7212 l
250.9169 154.3479 l
f*
222.9171 239.5772 m
251.4169 239.5772 l
251.4169 239.0771 l
222.9171 239.0771 l
f*
251.4169 239.0771 m
251.4169 154.8479 l
250.9169 154.8479 l
250.9169 239.0771 l
f*
222.9171 300.873 m
251.4169 300.873 l
251.4169 300.3729 l
222.9171 300.3729 l
f*
251.4169 300.3729 m
251.4169 239.5772 l
250.9169 239.5772 l
250.9169 300.3729 l
f*
222.9171 362.0772 m
251.4169 362.0772 l
251.4169 361.5772 l
222.9171 361.5772 l
f*
251.4169 361.5772 m
251.4169 300.873 l
250.9169 300.873 l
250.9169 361.5772 l
f*
222.9171 403.8049 m
251.4169 403.8049 l
251.4169 403.3049 l
222.9171 403.3049 l
f*
251.4169 403.3049 m
251.4169 362.0772 l
250.9169 362.0772 l
250.9169 403.3049 l
f*
222.9171 457.0778 m
251.4169 457.0778 l
251.4169 456.5778 l
222.9171 456.5778 l
f*
251.4169 456.5778 m
251.4169 403.8049 l
250.9169 403.8049 l
250.9169 456.5778 l
f*
222.9171 499.7735 m
251.4169 499.7735 l
251.4169 499.2735 l
222.9171 499.2735 l
f*
251.4169 499.2735 m
251.4169 457.0778 l
250.9169 457.0778 l
250.9169 499.2735 l
f*
222.9171 544.2854 m
251.4169 544.2854 l
251.4169 543.7854 l
222.9171 543.7854 l
f*
251.4169 543.7854 m
251.4169 499.7735 l
250.9169 499.7735 l
250.9169 543.7854 l
f*
222.9171 634.0493 m
251.4169 634.0493 l
251.4169 633.5493 l
222.9171 633.5493 l
f*
251.4169 633.5493 m
251.4169 544.2854 l
250.9169 544.2854 l
250.9169 633.5493 l
f*
251.4169 713.2859 m
251.4169 634.0493 l
250.9169 634.0493 l
250.9169 713.2859 l
f*
251.4169 109.7212 m
262.9168 109.7212 l
262.9168 109.2212 l
251.4169 109.2212 l
f*
262.9168 109.2212 m
262.9168 83.2859 l
262.4168 83.2859 l
262.4168 109.2212 l
f*
262.9168 713.2859 m
262.9168 109.7212 l
262.4168 109.7212 l
262.4168 713.2859 l
f*
262.9168 109.7212 m
299.9166 109.7212 l
299.9166 109.2212 l
262.9168 109.2212 l
f*
299.9166 109.2212 m
299.9166 83.2859 l
299.4165 83.2859 l
299.4165 109.2212 l
f*
262.9168 154.8479 m
299.9166 154.8479 l
299.9166 154.3479 l
262.9168 154.3479 l
f*
299.9166 154.3479 m
299.9166 109.7212 l
299.4165 109.7212 l
299.4165 154.3479 l
f*
262.9168 239.5772 m
299.9166 239.5772 l
299.9166 239.0771 l
262.9168 239.0771 l
f*
299.9166 239.0771 m
299.9166 154.8479 l
299.4165 154.8479 l
299.4165 239.0771 l
f*
262.9168 300.873 m
299.9166 300.873 l
299.9166 300.3729 l
262.9168 300.3729 l
f*
299.9166 300.3729 m
299.9166 239.5772 l
299.4165 239.5772 l
299.4165 300.3729 l
f*
262.9168 362.0772 m
299.9166 362.0772 l
299.9166 361.5772 l
262.9168 361.5772 l
f*
299.9166 361.5772 m
299.9166 300.873 l
299.4165 300.873 l
299.4165 361.5772 l
f*
262.9168 403.8049 m
299.9166 403.8049 l
299.9166 403.3049 l
262.9168 403.3049 l
f*
299.9166 403.3049 m
299.9166 362.0772 l
299.4165 362.0772 l
299.4165 403.3049 l
f*
262.9168 457.0778 m
299.9166 457.0778 l
299.9166 456.5778 l
262.9168 456.5778 l
f*
299.9166 456.5778 m
299.9166 403.8049 l
299.4165 403.8049 l
299.4165 456.5778 l
f*
262.9168 499.7735 m
299.9166 499.7735 l
299.9166 499.2735 l
262.9168 499.2735 l
f*
299.9166 499.2735 m
299.9166 457.0778 l
299.4165 457.0778 l
299.4165 499.2735 l
f*
262.9168 544.2854 m
299.9166 544.2854 l
299.9166 543.7854 l
262.9168 543.7854 l
f*
299.9166 543.7854 m
299.9166 499.7735 l
299.4165 499.7735 l
299.4165 543.7854 l
f*
262.9168 634.0493 m
299.9166 634.0493 l
299.9166 633.5493 l
262.9168 633.5493 l
f*
299.9166 633.5493 m
299.9166 544.2854 l
299.4165 544.2854 l
299.4165 633.5493 l
f*
299.9166 713.2859 m
299.9166 634.0493 l
299.4165 634.0493 l
299.4165 713.2859 l
f*
299.9166 109.7212 m
336.9163 109.7212 l
336.9163 109.2212 l
299.9166 109.2212 l
f*
336.9163 109.2212 m
336.9163 83.2859 l
336.4163 83.2859 l
336.4163 109.2212 l
f*
299.9166 154.8479 m
336.9163 154.8479 l
336.9163 154.3479 l
299.9166 154.3479 l
f*
336.9163 154.3479 m
336.9163 109.7212 l
336.4163 109.7212 l
336.4163 154.3479 l
f*
299.9166 239.5772 m
336.9163 239.5772 l
336.9163 239.0771 l
299.9166 239.0771 l
f*
336.9163 239.0771 m
336.9163 154.8479 l
336.4163 154.8479 l
336.4163 239.0771 l
f*
299.9166 300.873 m
336.9163 300.873 l
336.9163 300.3729 l
299.9166 300.3729 l
f*
336.9163 300.3729 m
336.9163 239.5772 l
336.4163 239.5772 l
336.4163 300.3729 l
f*
299.9166 362.0772 m
336.9163 362.0772 l
336.9163 361.5772 l
299.9166 361.5772 l
f*
336.9163 361.5772 m
336.9163 300.873 l
336.4163 300.873 l
336.4163 361.5772 l
f*
299.9166 403.8049 m
336.9163 403.8049 l
336.9163 403.3049 l
299.9166 403.3049 l
f*
336.9163 403.3049 m
336.9163 362.0772 l
336.4163 362.0772 l
336.4163 403.3049 l
f*
299.9166 457.0778 m
336.9163 457.0778 l
336.9163 456.5778 l
299.9166 456.5778 l
f*
336.9163 456.5778 m
336.9163 403.8049 l
336.4163 403.8049 l
336.4163 456.5778 l
f*
299.9166 499.7735 m
336.9163 499.7735 l
336.9163 499.2735 l
299.9166 499.2735 l
f*
336.9163 499.2735 m
336.9163 457.0778 l
336.4163 457.0778 l
336.4163 499.2735 l
f*
299.9166 544.2854 m
336.9163 544.2854 l
336.9163 543.7854 l
299.9166 543.7854 l
f*
336.9163 543.7854 m
336.9163 499.7735 l
336.4163 499.7735 l
336.4163 543.7854 l
f*
299.9166 634.0493 m
336.9163 634.0493 l
336.9163 633.5493 l
299.9166 633.5493 l
f*
336.9163 633.5493 m
336.9163 544.2854 l
336.4163 544.2854 l
336.4163 633.5493 l
f*
336.9163 713.2859 m
336.9163 634.0493 l
336.4163 634.0493 l
336.4163 713.2859 l
f*
336.9163 109.7212 m
373.9161 109.7212 l
373.9161 109.2212 l
336.9163 109.2212 l
f*
373.9161 109.2212 m
373.9161 83.2859 l
373.4161 83.2859 l
373.4161 109.2212 l
f*
336.9163 154.8479 m
373.9161 154.8479 l
373.9161 154.3479 l
336.9163 154.3479 l
f*
373.9161 154.3479 m
373.9161 109.7212 l
373.4161 109.7212 l
373.4161 154.3479 l
f*
336.9163 239.5772 m
373.9161 239.5772 l
373.9161 239.0771 l
336.9163 239.0771 l
f*
373.9161 239.0771 m
373.9161 154.8479 l
373.4161 154.8479 l
373.4161 239.0771 l
f*
336.9163 300.873 m
373.9161 300.873 l
373.9161 300.3729 l
336.9163 300.3729 l
f*
373.9161 300.3729 m
373.9161 239.5772 l
373.4161 239.5772 l
373.4161 300.3729 l
f*
336.9163 362.0772 m
373.9161 362.0772 l
373.9161 361.5772 l
336.9163 361.5772 l
f*
373.9161 361.5772 m
373.9161 300.873 l
373.4161 300.873 l
373.4161 361.5772 l
f*
336.9163 403.8049 m
373.9161 403.8049 l
373.9161 403.3049 l
336.9163 403.3049 l
f*
373.9161 403.3049 m
373.9161 362.0772 l
373.4161 362.0772 l
373.4161 403.3049 l
f*
336.9163 457.0778 m
373.9161 457.0778 l
373.9161 456.5778 l
336.9163 456.5778 l
f*
373.9161 456.5778 m
373.9161 403.8049 l
373.4161 403.8049 l
373.4161 456.5778 l
f*
336.9163 499.7735 m
373.9161 499.7735 l
373.9161 499.2735 l
336.9163 499.2735 l
f*
373.9161 499.2735 m
373.9161 457.0778 l
373.4161 457.0778 l
373.4161 499.2735 l
f*
336.9163 544.2854 m
373.9161 544.2854 l
373.9161 543.7854 l
336.9163 543.7854 l
f*
373.9161 543.7854 m
373.9161 499.7735 l
373.4161 499.7735 l
373.4161 543.7854 l
f*
336.9163 634.0493 m
373.9161 634.0493 l
373.9161 633.5493 l
336.9163 633.5493 l
f*
373.9161 633.5493 m
373.9161 544.2854 l
373.4161 544.2854 l
373.4161 633.5493 l
f*
373.9161 713.2859 m
373.9161 634.0493 l
373.4161 634.0493 l
373.4161 713.2859 l
f*
373.9161 109.7212 m
385.416 109.7212 l
385.416 109.2212 l
373.9161 109.2212 l
f*
385.416 109.2212 m
385.416 83.2859 l
384.916 83.2859 l
384.916 109.2212 l
f*
385.416 713.2859 m
385.416 109.7212 l
384.916 109.7212 l
384.916 713.2859 l
f*
385.416 109.7212 m
405.4158 109.7212 l
405.4158 109.2212 l
385.416 109.2212 l
f*
405.4158 109.2212 m
405.4158 83.2859 l
404.9158 83.2859 l
404.9158 109.2212 l
f*
385.416 154.8479 m
405.4158 154.8479 l
405.4158 154.3479 l
385.416 154.3479 l
f*
405.4158 154.3479 m
405.4158 109.7212 l
404.9158 109.7212 l
404.9158 154.3479 l
f*
385.416 239.5772 m
405.4158 239.5772 l
405.4158 239.0771 l
385.416 239.0771 l
f*
405.4158 239.0771 m
405.4158 154.8479 l
404.9158 154.8479 l
404.9158 239.0771 l
f*
385.416 300.873 m
405.4158 300.873 l
405.4158 300.3729 l
385.416 300.3729 l
f*
405.4158 300.3729 m
405.4158 239.5772 l
404.9158 239.5772 l
404.9158 300.3729 l
f*
385.416 362.0772 m
405.4158 362.0772 l
405.4158 361.5772 l
385.416 361.5772 l
f*
405.4158 361.5772 m
405.4158 300.873 l
404.9158 300.873 l
404.9158 361.5772 l
f*
385.416 403.8049 m
405.4158 403.8049 l
405.4158 403.3049 l
385.416 403.3049 l
f*
405.4158 403.3049 m
405.4158 362.0772 l
404.9158 362.0772 l
404.9158 403.3049 l
f*
385.416 457.0778 m
405.4158 457.0778 l
405.4158 456.5778 l
385.416 456.5778 l
f*
405.4158 456.5778 m
405.4158 403.8049 l
404.9158 403.8049 l
404.9158 456.5778 l
f*
385.416 499.7735 m
405.4158 499.7735 l
405.4158 499.2735 l
385.416 499.2735 l
f*
405.4158 499.2735 m
405.4158 457.0778 l
404.9158 457.0778 l
404.9158 499.2735 l
f*
385.416 544.2854 m
405.4158 544.2854 l
405.4158 543.7854 l
385.416 543.7854 l
f*
405.4158 543.7854 m
405.4158 499.7735 l
404.9158 499.7735 l
404.9158 543.7854 l
f*
385.416 634.0493 m
405.4158 634.0493 l
405.4158 633.5493 l
385.416 633.5493 l
f*
405.4158 633.5493 m
405.4158 544.2854 l
404.9158 544.2854 l
404.9158 633.5493 l
f*
405.4158 713.2859 m
405.4158 634.0493 l
404.9158 634.0493 l
404.9158 713.2859 l
f*
405.4158 109.7212 m
425.4157 109.7212 l
425.4157 109.2212 l
405.4158 109.2212 l
f*
425.4157 109.2212 m
425.4157 83.2859 l
424.9157 83.2859 l
424.9157 109.2212 l
f*
405.4158 154.8479 m
425.4157 154.8479 l
425.4157 154.3479 l
405.4158 154.3479 l
f*
425.4157 154.3479 m
425.4157 109.7212 l
424.9157 109.7212 l
424.9157 154.3479 l
f*
405.4158 239.5772 m
425.4157 239.5772 l
425.4157 239.0771 l
405.4158 239.0771 l
f*
425.4157 239.0771 m
425.4157 154.8479 l
424.9157 154.8479 l
424.9157 239.0771 l
f*
405.4158 300.873 m
425.4157 300.873 l
425.4157 300.3729 l
405.4158 300.3729 l
f*
425.4157 300.3729 m
425.4157 239.5772 l
424.9157 239.5772 l
424.9157 300.3729 l
f*
405.4158 362.0772 m
425.4157 362.0772 l
425.4157 361.5772 l
405.4158 361.5772 l
f*
425.4157 361.5772 m
425.4157 300.873 l
424.9157 300.873 l
424.9157 361.5772 l
f*
405.4158 403.8049 m
425.4157 403.8049 l
425.4157 403.3049 l
405.4158 403.3049 l
f*
425.4157 403.3049 m
425.4157 362.0772 l
424.9157 362.0772 l
424.9157 403.3049 l
f*
405.4158 457.0778 m
425.4157 457.0778 l
425.4157 456.5778 l
405.4158 456.5778 l
f*
425.4157 456.5778 m
425.4157 403.8049 l
424.9157 403.8049 l
424.9157 456.5778 l
f*
405.4158 499.7735 m
425.4157 499.7735 l
425.4157 499.2735 l
405.4158 499.2735 l
f*
425.4157 499.2735 m
425.4157 457.0778 l
424.9157 457.0778 l
424.9157 499.2735 l
f*
405.4158 544.2854 m
425.4157 544.2854 l
425.4157 543.7854 l
405.4158 543.7854 l
f*
425.4157 543.7854 m
425.4157 499.7735 l
424.9157 499.7735 l
424.9157 543.7854 l
f*
405.4158 634.0493 m
425.4157 634.0493 l
425.4157 633.5493 l
405.4158 633.5493 l
f*
425.4157 633.5493 m
425.4157 544.2854 l
424.9157 544.2854 l
424.9157 633.5493 l
f*
425.4157 713.2859 m
425.4157 634.0493 l
424.9157 634.0493 l
424.9157 713.2859 l
f*
458.1658 713.2859 m
458.1658 83.2859 l
457.6657 83.2859 l
457.6657 713.2859 l
f*
0.83 0.64 0.02 0 k
103.9748 516.8126 m
103.9748 524.5228 l
h
f*
183.9685 516.8126 m
183.9685 520.6677 l
h
f*
183.9685 522.652 m
183.9685 530.3622 l
h
f*
203.9811 516.8126 m
203.9811 524.5228 l
h
f*
203.9811 526.5071 m
203.9811 534.274 l
h
f*
272.4661 516.8126 m
272.4661 524.5228 l
h
f*
309.4866 516.8126 m
309.4866 520.6677 l
h
f*
309.4866 522.652 m
309.4866 530.3622 l
h
f*
355.011 504.737 m
355.011 508.5921 l
h
f*
355.011 510.5764 m
355.011 518.3433 l
h
f*
355.011 520.3276 m
355.011 528.0378 l
h
f*
355.011 530.022 m
355.011 537.7323 l
h
f*
471.2315 83.2819 m
471.2315 234.0283 l
h
f*
0 g
1 j
1 J
0 7.9999 -7.9999 0 40.9322 83.2818 cm
BT
/F3 1 Tf
1 TL
0 0 Td
(Table)Tj
2.8346 0 Td
(2.)Tj
/F0 1 Tf
1.3323 0 Td
(\()Tj
/F6 1 Tf
(Continue)Tj
4.2945 0 Td
(d)Tj
/F0 1 Tf
0.6378 0 Td
(\))Tj
ET
Q
q
1 j
1 J
0 w
0 6.9998 -6.9998 0 57.4299 83.2818 cm
BT
/F3 1 Tf
1 TL
0 0 Td
(Gene)Tj
4.0657 0 Td
(Genomic)Tj
0 -1.2148 Td
(coordinate)Tj
6.4469 1.2148 Td
(Nucleotide)Tj
5.3536 0 Td
(change)Tj
6.7465 0 Td
(Mutation)Tj
4.4141 0 Td
(type)Tj
4.3411 0 Td
(Amino)Tj
3.353 0 Td
(acid)Tj
-3.353 -1.2148 Td
(change)Tj
3.7418 0 Td
(\(rs)Tj
-3.7418 -1.2149 Td
(number)Tj
3.9038 0 Td
(in)Tj
-3.9038 -1.2149 Td
(dbSNP\))Tj
8.7471 3.6446 Td
(Allele)Tj
0 -1.2148 Td
(frequency)Tj
5.9609 1.2148 Td
(Frequency)Tj
5.2888 0 Td
(in)Tj
-5.2888 -1.2148 Td
(gnomAD)Tj
0 -1.2149 Td
(Database)Tj
0 -1.2149 Td
(\(East)Tj
2.6727 0 Td
(Asian\))Tj
4.9405 3.6446 Td
(Affected)Tj
0 -1.2148 Td
(patients)Tj
0 -1.2149 Td
(\(homo/)Tj
0 -1.2149 Td
(hetero\))Tj
6.0987 3.6446 Td
(Report)Tj
6.3578 0 Td
(Effect)Tj
12.8209 0 Td
(SIFT/Polyphen/)Tj
0 -1.2148 Td
(Mutation)Tj
4.414 0 Td
(taster)Tj
-4.414 -1.2149 Td
(prediction)Tj
5.0863 0 Td
(\(Clinical)Tj
-5.0863 -1.2149 Td
(significance)Tj
6.0258 0 Td
(based)Tj
3.1181 0 Td
(on)Tj
-9.1439 -1.2148 Td
(clinVar\))Tj
/F0 1 Tf
-74.7631 -1.6361 Td
(chr2:)Tj
0 -1.2148 Td
(21,263,900)Tj
6.4469 1.2148 Td
(c.C293T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.T98I)Tj
0 -1.2148 Td
(\(rs1367117\))Tj
8.747 1.2148 Td
(0.068)Tj
5.961 0 Td
(0.127)Tj
7.6051 0 Td
(0/3)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
6.366 0 Td
(Hypocholesterolemia)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2148 Td
(Polymorphism)Tj
0 -1.2149 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2149 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-41.7753 -1.6441 Td
(Variants)Tj
3.8875 0 Td
(of)Tj
1.0691 0 Td
(unknown)Tj
4.2116 0 Td
(frequency)Tj
-45.0798 -1.6441 Td
(chr2:)Tj
0 -1.2149 Td
(21,266,774)Tj
6.4469 1.2149 Td
(c.35_44TGGCGCT)Tj
8.5689 0 Td
(GC)Tj
3.5393 0 Td
(frameshift)Tj
0 -1.2149 Td
(substitution)Tj
8.7552 1.2149 Td
(NA)Tj
8.747 0 Td
(0.136)Tj
5.961 0 Td
(NA)Tj
7.6051 0 Td
(0/6)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
/F6 1 Tf
-66.2914 -2.859 Td
(PCSK9)Tj
/F0 1 Tf
43.9458 0 Td
(Rare)Tj
2.3893 0 Td
(variants)Tj
-42.1317 -1.636 Td
(chr1:)Tj
0 -1.2149 Td
(55,505,520)Tj
6.4469 1.2149 Td
(c.G10A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.V4I)Tj
0 -1.2149 Td
(\(rs186669805\))Tj
8.747 1.2149 Td
(0.023)Tj
5.961 0 Td
(0.002)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(])Tj
6.366 0 Td
(Hypercholesterolemia)Tj
12.8209 0 Td
(Tolerated/Benign/B/)Tj
0 -1.2149 Td
(polymorphism)Tj
6.4388 0 Td
(\(NA\))Tj
-81.3477 -1.6441 Td
(chr1:)Tj
0 -1.2149 Td
(55,509,585)Tj
6.4469 1.2149 Td
(c.C277T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.R93C)Tj
0 -1.2149 Td
(\(rs151193009\))Tj
8.747 1.2149 Td
(0.023)Tj
5.961 0 Td
(0.009)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(])Tj
6.366 0 Td
(Hypocholesterolemia)Tj
12.8209 0 Td
(Tolerated/probably)Tj
0 -1.2149 Td
(damaging/D/)Tj
0 -1.2149 Td
(polymorphism)Tj
6.4388 0 Td
(\(Benign\))Tj
-81.3477 -1.6441 Td
(chr1:)Tj
0 -1.2149 Td
(55,524,312)Tj
6.4469 1.2149 Td
(c.C1495T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.R499C)Tj
0 -1.2149 Td
(\(rs201395805\))Tj
8.747 1.2149 Td
(0.023)Tj
/F9 1 Tf
5.961 0 Td
[( )]TJ
/F0 1 Tf
(0.001)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/probably)Tj
0 -1.2149 Td
(damaging/)Tj
0 -1.2148 Td
(polymorphism)Tj
6.4388 0 Td
(\(NA\))Tj
-42.5448 -1.6442 Td
(Common)Tj
4.2764 0 Td
(variants)Tj
-43.0793 -1.636 Td
(chr1:)Tj
0 -1.2148 Td
(55,505,668)Tj
6.4469 1.2148 Td
(c.C158T)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2148 Td
(SNV)Tj
8.7552 1.2148 Td
(p.A53V)Tj
0 -1.2148 Td
(\(rs11583680\))Tj
8.747 1.2148 Td
(0.091)Tj
5.961 0 Td
(0.122)Tj
7.6051 0 Td
(0/4)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(])Tj
6.366 0 Td
(Unknown)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2148 Td
(Polymorphism)Tj
0 -1.2149 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2149 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-77.6869 -1.6441 Td
(chr1:)Tj
0 -1.2149 Td
(55,524,237)Tj
6.4469 1.2149 Td
(c.G1420A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.V474I)Tj
0 -1.2149 Td
(\(rs562556\))Tj
8.747 1.2149 Td
(0.409)Tj
5.961 0 Td
(0.993)Tj
7.6051 0 Td
(8/2)Tj
6.0986 0 Td
(Yes[)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(])Tj
6.366 0 Td
(Hypocholesterolemia;)Tj
0 -1.2149 Td
(familial)Tj
0 -1.2149 Td
(hypercholesterolemia)Tj
12.8209 2.4298 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(Polymorphism)Tj
0 -1.2149 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2148 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-77.6869 -1.6441 Td
(chr1:)Tj
0 -1.2149 Td
(55,529,187)Tj
6.4469 1.2149 Td
(c.G2009A)Tj
12.1082 0 Td
(nonsynonymous)Tj
0 -1.2149 Td
(SNV)Tj
8.7552 1.2149 Td
(p.G670E)Tj
0 -1.2149 Td
(\(rs505151\))Tj
8.747 1.2149 Td
(0.500)Tj
5.961 0 Td
(0.948)Tj
7.6051 0 Td
(10/2)Tj
6.0986 0 Td
(Yes)Tj
0 -1.2149 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(])Tj
6.366 1.2149 Td
(Hypocholesterolemia)Tj
12.8209 0 Td
(Tolerated/Benign/)Tj
0 -1.2149 Td
(Polymorphism)Tj
0 -1.2149 Td
(automatic)Tj
4.5598 0 Td
(\(Benign/)Tj
-4.5598 -1.2149 Td
(Likely)Tj
2.778 0 Td
(benign\))Tj
-41.7753 -1.636 Td
(Variants)Tj
3.8875 0 Td
(of)Tj
1.0691 0 Td
(unknown)Tj
4.2116 0 Td
(frequency)Tj
-45.0798 -1.6441 Td
(chr1:)Tj
0 -1.2149 Td
(55,505,552)Tj
6.4469 1.2149 Td
(c.42_43insCTGCT)Tj
8.2773 0 Td
(GCTG)Tj
3.8309 0 Td
(nonframeshift)Tj
0 -1.2149 Td
(substitution)Tj
8.7552 1.2149 Td
(p.P14delinsPLLL)Tj
8.747 0 Td
(0.091)Tj
5.961 0 Td
(NA)Tj
7.6051 0 Td
(0/4)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
-62.088 -2.859 Td
(chr1:)Tj
0 -1.2149 Td
(55,529,225)Tj
6.4469 1.2149 Td
(c.2048dupA)Tj
12.1082 0 Td
(frameshift)Tj
0 -1.2149 Td
(substitution)Tj
8.7552 1.2149 Td
(p.H683fs)Tj
8.747 0 Td
(0.023)Tj
5.961 0 Td
(NA)Tj
7.6051 0 Td
(0/1)Tj
6.0986 0 Td
(No)Tj
6.366 0 Td
(Unknown)Tj
ET
Q
q
1 j
1 J
0 w
0 7.9999 -7.9999 0 441.1842 83.2818 cm
BT
/F0 1 Tf
1 TL
0 0 Td
(SNV:)Tj
2.5582 0 Td
(single)Tj
2.8134 0 Td
(nucleotide)Tj
4.7481 0 Td
(variant,)Tj
3.4867 0 Td
(NA:)Tj
1.8921 0 Td
(not)Tj
1.6158 0 Td
(available)Tj
/F5 1 Tf
-17.1143 -1.4952 Td
[()]TJ
/F0 1 Tf
(:)Tj
1.063 0 Td
(reported)Tj
3.926 0 Td
(in)Tj
0.9992 0 Td
(genomA)Tj
3.6921 0 Td
(D)Tj
0.9497 0 Td
(browser)Tj
0.83 0.64 0.02 0 k
/F11 1 Tf
-0.025 Tc
-10.63 -2.126 Td
(https://doi.)Tj
3.9756 0 Td
(org/10.1371/j)Tj
5.0244 0 Td
(ournal.pone)Tj
4.4079 0 Td
(.0186446.t002)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 437.8393 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Genetic)Tj
3.6142 0 Td
(variants)Tj
3.6567 0 Td
(in)Tj
0.9779 0 Td
(extremely)Tj
4.4859 0 Td
(low)Tj
1.6866 0 Td
(LDL-C)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01864)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(16,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(6)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
125 0 obj
<>stream
endstream
endobj
126 0 obj
<>stream
endstream
endobj
127 0 obj
<>stream
endstream
endobj
128 0 obj
<>stream
endstream
endobj
129 0 obj
<>stream
endstream
endobj
130 0 obj
<>stream
BT
66.402 0 Td
(13)Tj
ET
Q
endstream
endobj
131 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 133 0 R/Contents 134 0 R/TrimBox[0 0 612 792]>>
endobj
132 0 obj
<>stream
xݿ4Y(s Ȥf%|080p"
'1&2
N"& L` p\ZPgUUP]U<{{u? _o @ @ @ n??!E O@; @ @ @ z @1t, @ @ @mb{$J o+ @ @ /#%D@
@ @ p% @@?1
dD @ @ H .CwB @ @ & ~IG O@ @ @ @ b