Conceived and designed the experiments: SS RO. Performed the experiments: SM KHBGK CC. Analyzed the data: SM CC. Contributed reagents/materials/analysis tools: RO SS. Wrote the paper: SS.
The authors have declared that no competing interests exist.
Genetic individuality is the foundation of personalized medicine, yet its determinants are currently poorly understood. One issue is the difference between monozygotic twins that are assumed identical and have been extensively used in genetic studies for decades
Genome-wide constancy and change underlies evolution and familial inheritance but remains ill-defined. An assessment of changes as the genome is passed on from one generation (meiosis) and developmental cycle (mitosis) to the next is needed. It directly contributes to the sum of genetic individuality. At present, these inquiries are difficult
CNVs are structural variants that are both frequent and relevant and may range in size in humans from 1 Kb to several Mb
Studies on these two genome-wide variations (SNPs and CNVs) have greatly enhanced our understanding of evolution and genetic individuality. They are also helping to elucidate the cause of genetic, and genomic disorders including schizophrenia
Members of the family one are indicated with (I-) and members of the family two are indicated with (II-). The designations included in this figure are followed in subsequent figures and tables.
Family 1 | Family 2 | |||||||
I-1-1 | I-1-2 | I-2-1 | I-2-2 | II-1-1 | II-1-2 | II-2-1 | II-2-2 | |
|
82 | 74 | 53 | 53 | N/A | N/A | 43 | 43 |
|
Male | Female | Female | Female | Male | Female | Female | Female |
|
Afro-American | Caucasian | ||||||
|
Compulsive Personality Disorder | N/A | Schizophrenia, Paranoid Type, onset age 22 | Bipolar I Disorder, onset age 52 | Major depression and panic disorder for 6 months after cardiac surgery, onset age 73 | N/A | Schizoaffective Disorder, onset age 27 | Single episode of Major Depression, fully remitted, onset age 18 |
Demography and Clinical History of monozygotic (MZ) twins discordant for Schizophrenia (SCZ). Family one is indicated with (I), family two is indicated with (II). N/A = Not Applicable.
The number of CNVs per individual ranged from 35 to 65, with the exception of one individual who is described more fully later (
These include LINE (blue), SINE (purple), LTR (yellow), Satellite (sky blue), simple repeats (black) and low complexity repeats (green) with numerical values on top of the bars representing percentage of that repeat.
CNV Size | Family 1 | Family 2 | ||||||
I-1-1 | I-1-2 | I-2-1 | I-2-2 | II-1-1 | II-1-2 | II-2-1 | II-2-2 | |
|
0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 |
|
17 | 18 | 15 | 20 | 119 | 50 | 24 | 24 |
|
11 | 6 | 4 | 10 | 25 | 6 | 13 | 9 |
|
5 | 5 | 6 | 5 | 11 | 3 | 1 | 4 |
|
2 | 0 | 2 | 2 | 6 | 1 | 1 | 2 |
|
6 | 2 | 4 | 7 | 7 | 2 | 5 | 2 |
|
9 | 4 | 5 | 3 | 5 | 2 | 4 | 5 |
|
5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
|
3 | 0 | 0 | 0 | 2 | 0 | 2 | 2 |
|
|
|
|
|
|
|
|
|
Numerical values in each cell of the table indicate how many CNVs of that particular size range were observed in that particular individual.
CNVs | Family 1 | Family 2 | ||||||
I-1-1 | I-1-2 | I-2-1 | I-2-2 | II-1-1 | II-1-2 | II-2-1 | II-2-2 | |
|
21 | 6 | 5 | 6 | 52 | 11 | 6 | 4 |
|
37 | 29 | 31 | 41 | 125 | 53 | 44 | 45 |
|
1 | 1 | 0 | 2 | 42 | 6 | 1 | 0 |
|
57 | 34 | 36 | 45 | 135 | 58 | 49 | 49 |
|
|
|
|
|
|
|
|
|
Frequency of CNVs which are losses (deletion) or gains (duplication) and characterization as present or absent from The Database of Genomic Variants (DGV).
Chr No. | Family 1 | Family 2 | ||||||
I-1-1 | I-1-2 | I-2-1 | I-2-2 | II-1-1 | II-1-2 | II-2-1 | II-2-2 | |
|
4 | 2 | 2 | 2 | 11 | 2 | 6 | 6 |
|
4 | 2 | 5 | 5 | 11 | 2 | 2 | 3 |
|
1 | 4 | 2 | 3 | 7 | 4 | 4 | 2 |
|
4 | 3 | 2 | 4 | 8 | 1 | 3 | 2 |
|
0 | 0 | 0 | 0 | 12 | 0 | 2 | 1 |
|
0 | 0 | 0 | 0 | 10 | 2 | 0 | 0 |
|
2 | 6 | 3 | 4 | 10 | 5 | 3 | 4 |
|
1 | 0 | 3 | 3 | 7 | 3 | 3 | 3 |
|
1 | 1 | 2 | 3 | 4 | 4 | 3 | 4 |
|
2 | 1 | 1 | 1 | 3 | 5 | 1 | 1 |
|
3 | 1 | 2 | 1 | 5 | 1 | 2 | 2 |
|
0 | 1 | 0 | 1 | 4 | 3 | 0 | 1 |
|
0 | 0 | 0 | 0 | 40 | 1 | 1 | 0 |
|
4 | 6 | 3 | 5 | 4 | 6 | 5 | 3 |
|
4 | 3 | 1 | 3 | 2 | 6 | 6 | 8 |
|
2 | 1 | 2 | 3 | 9 | 1 | 1 | 1 |
|
4 | 1 | 2 | 3 | 8 | 2 | 2 | 1 |
|
0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
|
0 | 1 | 0 | 0 | 7 | 3 | 2 | 1 |
|
0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
|
1 | 2 | 2 | 3 | 2 | 3 | 2 | 1 |
|
3 | 0 | 3 | 2 | 3 | 1 | 1 | 1 |
|
18 | 0 | 1 | 1 | 9 | 9 | 1 | 2 |
|
|
|
|
|
|
|
|
|
Chromosome specific distribution of
Chr. No = Chromosome number.
A novel feature of the data included in this report is that we are able to classify observed CNVs into two groups based on their absence or presence in one of the parents. CNVs that were found in one or both twins and not seen in either parent, were classified as
Sl. No | Location | Family 1 | Status | Meiosis | Mitosis | Novel | Genes (Overlapping or Nearby) | SD | |||||
I-2-1 | Size (kb) | Breakpoints | I-2-2 | Size (kb) | Breakpoints | ||||||||
1 |
|
Yes | 112 | 16724089…16835888 |
|
|
NBPF1, NBPF10 | 1 | |||||
2 |
|
Yes | 152 | 1407209…1559511 | Yes | 152 | 1407209…1559511 |
|
|
TPO | 0 | ||
3 |
|
Yes | 1147 | 89862331…91008912 | Yes | 1159 | 89850279…91008912 |
|
|
0 | |||
4 |
|
Yes | 191 | 132801221…132992517 |
|
|
1 | ||||||
5 |
|
Yes | 118 | 64706066…64823721 | Yes | 118 | 64704377…64822216 |
|
|
1 | |||
6 |
|
Yes | 126 | 7847289…7973253 |
|
|
1 | ||||||
7 |
|
Yes | 336 | 47045602…47381308 | Yes | 250 | 47131383…47381308 |
|
|
0 | |||
8 |
|
Yes | 154 | 48178242…48332398 |
|
|
|
|
0 | ||||
9 |
|
Yes | 569 | 45361389…45929992 |
|
|
FAM27A | 1 | |||||
10 |
|
Yes | 141 | 38777481…38918566 |
|
|
1 | ||||||
11 |
|
Yes | 861 | 65412415…66273526 |
|
|
1 | ||||||
12 |
|
Yes | 196 | 8303317…8499801 |
|
|
CLEC6A | 1 | |||||
13 |
|
Yes | 103 | 89780137…89883415 |
|
|
|
|
0 | ||||
14 |
|
Yes | 119 | 13891136…14009908 |
|
|
ANKRD21, LOC441956 | 1 | |||||
15 |
|
Yes | 149 | 47917899…48066856 | Yes | 149 | 47917899…48066856 |
|
|
SSX5, SSX1, SSX9 | 0 |
Sl. No | Location | Family 2 | Status | Meiosis | Mitosis | Novel | Genes (Overlapping or Nearby) | SD | |||||
II-2-1 | Size (kb) | Breakpoints | II-2-2 | Size (kb) | Breakpoints | ||||||||
1 |
|
Yes | 120 | 143867807…143987616 |
|
|
NOTCH2NL | 0 | |||||
2 |
|
Yes | 104 | 147353175…147456930 | Yes | 104 | 147353175…147456930 |
|
|
0 | |||
3 |
|
Yes | 119 | 241230453…241349107 |
|
|
0 | ||||||
4 |
|
Yes | 155 | 126958012…127112518 |
|
|
1 | ||||||
5 |
|
Yes | 299 | 48986100…49285347 |
|
|
0 | ||||||
6 |
|
Yes | 101 | 770367…871743 | Yes | 107 | 770367…877436 |
|
|
ZDHHC11 | 1 | ||
7 |
|
Yes | 151 | 34119387…34269887 |
|
|
1 | ||||||
8 |
|
Yes | 202 | 61761008…61962936 |
|
|
0 | ||||||
9 |
|
Yes | 116 | 64588316…64704125 | Yes | 125 | 64579322…64704125 |
|
|
1 | |||
10 |
|
Yes | 100 | 142956516…143056637 |
|
|
LOC441294, FAM139A | 1 | |||||
11 |
|
Yes | 220 | 12071704…12291845 | Yes | 220 | 12071704…12291845 |
|
|
FAM86B1, DEFB130 | 0 | ||
12 |
|
Yes | 2720 | 41465094…44184864 | Yes | 1901 | 42249132…44149779 |
|
|
ANKRD20A2, ANKRD20A3, FOXD4L4, FOXD4L2 | 1 | ||
13 |
|
Yes | 250 | 67416254…67665974 |
|
|
ANKRD20A1, ANKRD20A3 | 1 | |||||
14 |
|
Yes | 267 | 67239223…67505822 | Yes | 139 | 67239223…67378031 |
|
|
1 | |||
15 |
|
Yes | 189 | 8310909…8499801 |
|
|
1 | ||||||
16 |
|
Yes | 208 | 18138676…18346383 |
|
|
1 | ||||||
17 |
|
Yes | 601 | 18072112…18672662 | Yes | 601 | 18072112…18672662 |
|
|
OR11H12, ACTBL1 | 1 | ||
18 |
|
Yes | 106 | 18276329…18382609 |
|
|
1 | ||||||
19 |
|
Yes | 203 | 19882763…20085783 | Yes | 221 | 19864583…20085783 |
|
|
OR4M2, OR4N4, LOC650137 | 1 | ||
20 |
|
Yes | 227 | 26808083…27035216 |
|
|
APBA2 | 0 | |||||
21 |
|
Yes | 110 | 28452853…28563274 |
|
|
CHRFAM7A | 1 | |||||
22 |
|
Yes | 199 | 22127012…22326425 |
|
|
0 | ||||||
23 |
|
Yes | 109 | 58847652…58957090 |
|
|
|
|
0 | ||||
24 |
|
Yes | 118 | 28147331…28264860 |
|
|
1 | ||||||
25 |
|
Yes | 3480 | 10106540…13586186 | Yes | 3814 | 9758730…13572586 |
|
|
BAGE2, BAGE4, BAGE | 0 |
Identity of
The genes overlapping disease specific
The genotypes generated by the Affymetrix 6.0 array have also allowed us to establish that ∼0.12% (1086 and 1022 in twin pair 1 and 2 respectively; 11 substitutions shared by both pairs) of the SNPs in the twins represented
We have been able to establish genome-wide (CNVs and SNPs) discordance for MZ twin pairs. Also, given that the twins are discordant for schizophrenia, it is possible to assign provisional CNVs (and genes) as well as substitutions (SNPs) that may be associated with the disease status of the affected twins in family 1 and family 2 (
Sl. No | Location | Family 1 | Status | Novel | Genes (Overlapping or Nearby) | SD | |||||||||||
I-1-1 | Size(kb) | Breakpoints | I-1-2 | Size(kb) | Breakpoints | I-2-1 | Size(kb) | Breakpoints | I-2-2 | Size(kb) | Breakpoints | ||||||
1 | 1p36.33 | Yes | 167 | 51586…218557 | Yes | 707 | 51586…758644 | Yes | 707 | 51586…758644 |
|
OR4F5, OR4F3, OR4F16, OR4F29 | 1 | ||||
2 | 1q21.1 | Yes | 765 | 147303136…148068045 | Yes | 734 | 147311699…148045353 | Yes | 577 | 147381253…147958358 |
|
PPIAL4, FCGR1A, HIST2H2BF | 1 | ||||
3 | 2p11.2 | Yes | 338 | 88917155…89254935 | Yes | 322 | 88914734…89236978 | Yes | 325 | 88917155…89242149 | Yes | 327 | 88914734…89242149 |
|
1 | ||
4 | 2p11.1 | Yes | 138 | 91017077…91154841 | Yes | 143 | 91017077…91160399 | Yes | 137 | 91017077…91154463 |
|
1 | |||||
5 | 2q21.2 | Yes | 236 | 132597824…132833718 | Yes | 222 | 132597824…132819911 | Yes | 222 | 132597824…132819911 |
|
1 | |||||
6 | 3p12.3 | Yes | 306 | 75677859…75984129 | Yes | 380 | 75597086…75977210 | Yes | 182 | 75583442…75764996 | Yes | 402 | 75582277…75984129 |
|
1 | ||
7 | 3q21.2 | Yes | 132 | 126907150…127039328 | Yes | 185 | 126907150…127091652 |
|
1 | ||||||||
8 | 3q21.3 | Yes | 170 | 131198515…131368353 | Yes | 166 | 131213377…131379054 | Yes | 176 | 131214431…131389948 |
|
1 | |||||
9 | 4p16.2 | Yes | 196 | 4040542…4236511 | Yes | 363 | 3873500…4236511 | Yes | 366 | 3870638…4236511 |
|
0 | |||||
10 | 4p11 | Yes | 436 | 48849363…49285347 | Yes | 497 | 48788531…49285347 | Yes | 497 | 48788531…49285347 |
|
1 | |||||
11 | 4q35.2 | Yes | 232 | 191021837…191254119 | Yes | 195 | 191059369…191254119 | Yes | 223 | 191031042…191254119 |
|
FRG1, TUBB4Q, FRG2, DUX4 | 0 | ||||
12 | 7p11.1 | Yes | 231 | 57523223…57753919 | Yes | 101 | 57640100…57741512 | Yes | 315 | 57640100…57954861 | Yes | 117 | 57640100…57757406 |
|
1 | ||
13 | 7q11.21 | Yes | 112 | 61365830…61477958 | Yes | 111 | 61365830…61476918 |
|
0 | ||||||||
14 | 7q11.21 | Yes | 253 | 64320173…64573380 | Yes | 415 | 64204380…64619667 | Yes | 385 | 64204380…64589253 |
|
ZNF92 | 0 | ||||
15 | 8p23.1 | Yes | 694 | 7209579…7903560 | Yes | 215 | 7027251…7242508 | Yes | 270 | 7021193…7291135 |
|
DEFB103A, DEFB103B, SPAG11B, DEFB104B, DEFB104A, DEFB106B, DEFB106A, DEFB105B, DEFB105A, DEFB107B, DEFB107A, SPAG11A, DEFB4 | 2 | ||||
16 | 9q12 | Yes | 690 | 68115006…68805366 | Yes | 1141 | 68115006…69256300 | Yes | 694 | 68115006…68809437 |
|
FOXD4L6, CBWD6, ANKRD20A4, CCDC29 | 1 | ||||
17 | 10q11.1 | Yes | 183 | 41972779…42155347 | Yes | 105 | 41934430…42039743 | Yes | 183 | 41972779…42155347 | Yes | 239 | 41934430…42173117 |
|
1 | ||
18 | 11p15.4 | Yes | 175 | 3405799…3580813 | Yes | 131 | 3430789…3561991 | Yes | 139 | 3430789…3569305 | Yes | 156 | 3406002…3561991 |
|
1 | ||
19 | 11q13.2 | Yes | 227 | 67239223…67466368 | Yes | 193 | 67273413…67466368 |
|
1 | ||||||||
20 | 14q11.1 | Yes | 1322 | 18138794…19460382 | Yes | 1103 | 18072112…19175240 | Yes | 705 | 18072112…18776746 | Yes | 705 | 18072112…18776746 |
|
OR11H12, ACTBL1, OR4Q3, OR4M1, OR4N2, OR4K5 | 0 | |
21 | 14q32.33 | Yes | 126 | 105265510…105391419 | Yes | 167 | 105100670…105268160 | Yes | 632 | 105190672…105822317 | Yes | 181 | 105149735…105331052 |
|
0 | ||
Yes | 156 | 105413825…105569826 | Yes | 213 | 105289618…105502685 | Yes | 178 | 105827891…106005581 | Yes | 261 | 105341035…105601720 |
|
0 | ||||
Yes | 205 | 105612786…105818132 | Yes | 279 | 105508896…105788389 | Yes | 280 | 105612786…105892769 |
|
0 | |||||||
22 | 15q11.1 | Yes | 471 | 18370252…18841457 | Yes | 178 | 18522238…18700540 | Yes | 1223 | 18845990…20068512 | Yes | 562 | 18276329…18838423 |
|
LOC283755, POTE15, OR4M2 | 1 | |
Yes | 1177 | 18845990…20022565 | Yes | 344 | 18845990…19189673 | Yes | 1078 | 18845990…19923712 |
|
OR4N4, LOC650137 | 1 | ||||||
Yes | 264 | 19303160…19566863 |
|
1 | |||||||||||||
23 | 15q11.2 | Yes | 189 | 22026287…22214843 | Yes | 174 | 22026287…22200408 |
|
1 | ||||||||
24 | 16p11.2 | Yes | 1217 | 32303108…33520394 | Yes | 1297 | 32538757…33836128 | Yes | 1142 | 32538757…33680554 | Yes | 249 | 32538757…32787273 |
|
LOC729355, TP53TG3 | 1 | |
Yes | 752 | 32910319…33662480 |
|
1 | |||||||||||||
25 | 16p11.2 | Yes | 250 | 34374795…34624994 | Yes | 249 | 34375533…34624994 | Yes | 249 | 34375533…34624994 |
|
1 | |||||
26 | 17p11.2 | Yes | 140 | 20559979…20700133 | Yes | 164 | 20538867…20703365 |
|
1 | ||||||||
27 | 17q21.31 | Yes | 229 | 41521621…41750183 | Yes | 123 | 41521621…41644356 | Yes | 123 | 41521621…41644356 |
|
KIAA1267, LRRC37A | 0 | ||||
28 | 17q21.31 | Yes | 351 | 41756820…42107467 | Yes | 296 | 41811739…42107467 | Yes | 392 | 41700624…42092926 | Yes | 302 | 41700624…42002447 |
|
ARL17, LRRC37A2, NSF | 1 | |
29 | 21p11.2 | Yes | 204 | 9758730…9962501 | Yes | 204 | 9758730…9962501 | Yes | 204 | 9758730…9962501 |
|
TPTE | 0 | ||||
30 | 21p11.1 | Yes | 3411 | 10106540…13517603 | Yes | 3419 | 10106540…13525448 | Yes | 3419 | 10106540…13525448 | Yes | 3477 | 10106540…13583117 |
|
BAGE2, BAGE4, BAGE | 2 | |
31 | 22q11.1 | Yes | 339 | 14435171…14774593 | Yes | 320 | 14435207…14754960 | Yes | 320 | 14435207…14754960 |
|
ACTBL1 | 1 | ||||
32 | 22q11.21 | Yes | 124 | 20051708…20175282 | Yes | 136 | 20145854…20281562 | Yes | 136 | 20145854…20281562 |
|
HIC2, UBE2L3 | 1 | ||||
33 | 22q11.22 | Yes | 240 | 21292462…21532509 | Yes | 127 | 21327799…21454509 |
|
GGTL4 | 0 |
Sl. No | Location | Family 2 | Status | Novel | Genes (Overlapping or Nearby) | SD | |||||||||||
II-1-1 | Size(kb) | Breakpoints | II-1-2 | Size(kb) | Breakpoints | II-2-1 | Size(kb) | Breakpoints | II-2-2 | Size(kb) | Breakpoints | ||||||
1 | 1p36.33 | Yes | 707 | 51586…758644 | Yes | 537 | 218557…755132 |
|
OR4F5, OR4F3, OR4F16, OR4F29 | 1 | |||||||
2 | 1p36.13 | Yes | 117 | 16718622…16835888 | Yes | 167 | 16718622…16885360 | Yes | 345 | 16718622…17063437 |
|
NBPF1, NBPF10 | 1 | ||||
3 | 1p21.1 | Yes | 130 | 103910749…104041200 | Yes | 127 | 103931691…104058426 |
|
AMY2B, AMY2A, AMY1A, AMY1C, AMY1B | 1 | |||||||
4 | 1p11.2 | Yes | 21680 | 121045307…142725034 | Yes | 21725 | 121045307…142770353 | Yes | 21725 | 121045307…142770353 |
|
0 | |||||
5 | 1q23.3 | Yes | 121 | 159775403…159896554 | Yes | 116 | 159780383…159896554 | Yes | 121 | 159775403…159896554 |
|
FCGR3A, FCGR2C, FCGR3B | 1 | ||||
6 | 2p11.2 | Yes | 401 | 88925215…89326446 | Yes | 759 | 88914227…89673147 | Yes | 935 | 88926972…89861763 | Yes | 450 | 88914734…89365010 |
|
1 | ||
7 | 2p11.1 | Yes | 160 | 91017077…91176948 | Yes | 268 | 91017077…91285520 | Yes | 1275 | 89879561…91154463 |
|
1 | |||||
8 | 2q21.2 | Yes | 260 | 132593436…132853218 | Yes | 183 | 132597824…132780848 | Yes | 222 | 132597824…132819911 |
|
1 | |||||
9 | 3p12.3 | Yes | 260 | 75583442…75843060 | Yes | 226 | 75538978…75764996 | Yes | 260 | 75583442…75843060 | Yes | 182 | 75583442…75764996 |
|
1 | ||
10 | 3q12.2 | Yes | 108 | 101822746…101930873 | Yes | 102 | 101822746…101925168 |
|
GPR128, TFG | 0 | |||||||
11 | 3q21.3 | Yes | 141 | 131198817…131339424 | Yes | 195 | 131194669…131389948 | Yes | 199 | 131198515…131397648 |
|
1 | |||||
12 | 4p16.2 | Yes | 407 | 3870638…4278016 | Yes | 180 | 3964803…4144453 | Yes | 366 | 3870638…4236511 | Yes | 357 | 3870638…4227503 |
|
OTOP1 | 0 | |
13 | 4q35.2 | Yes | 200 | 191053845…191254119 | Yes | 226 | 191028537…191254119 | Yes | 158 | 191052245…191210542 |
|
FRG1, TUBB4Q, FRG2, DUX4 | 0 | ||||
14 | 7p22.1 | Yes | 157 | 6838697…6995298 | Yes | 155 | 6840798…6995298 |
|
1 | ||||||||
15 | 7p11.1 | Yes | 117 | 57640100…57757406 | Yes | 114 | 57640100…57753919 | Yes | 149 | 57604989…57753919 | Yes | 123 | 57597399…57720623 |
|
1 | ||
16 | 8p23.1 | Yes | 203 | 12415742…12618442 | Yes | 199 | 12415742…12614748 | Yes | 136 | 12415742…12551430 |
|
1 | |||||
17 | 8p11.23 | Yes | 139 | 39349470…39488053 | Yes | 151 | 39354748…39506110 | Yes | 133 | 39354748…39488053 | Yes | 151 | 39354748…39506110 |
|
0 | ||
18 | 9p11.2 | Yes | 21937 | 44336683…66273526 | Yes | 21015 | 45258754…66273526 | Yes | 21015 | 45258754…66273526 |
|
FAM27A, FAM75A7 | 0 | ||||
9q12 | Yes | 861 | 68352238…69213455 | Yes | 103 | 68115006…68218485 | Yes | 1180 | 68076544…69256300 | Yes | 1099 | 68115006…69213671 |
|
FOXD4L6, CBWD6, ANKRD20A4, CCDC29 | 1 | ||
Yes | 457 | 68352238…68809437 |
|
||||||||||||||
19 | 10q11.1 | Yes | 129 | 41974796…42103488 | Yes | 236 | 41934430…42170853 | Yes | 105 | 41934430…42039743 | Yes | 239 | 41934430…42173117 |
|
1 | ||
20 | 11p15.4 | Yes | 206 | 3383178…3588946 | Yes | 205 | 3376078…3580813 | Yes | 131 | 3430789…3561991 |
|
1 | |||||
21 | 14q11.2 | Yes | 186 | 21602854…21788783 | Yes | 172 | 21625813…21787161 |
|
0 | ||||||||
22 | 14q11.2 | Yes | 226 | 21804698…22030660 | Yes | 226 | 21804698…22030660 |
|
0 | ||||||||
23 | 14q32.33 | Yes | 386 | 105190672…105576359 | Yes | 253 | 105345270…105597999 | Yes | 411 | 105190672…105601397 | Yes | 336 | 105265510…105601397 |
|
0 | ||
24 | 14q32.33 | Yes | 137 | 105760582…105897672 | Yes | 173 | 105645593…105818132 | Yes | 150 | 105638133…105788389 | Yes | 182 | 105640496…105822317 |
|
0 | ||
25 | 15q11.2 | Yes | 156 | 18682380…18838423 | Yes | 183 | 18655531…18838423 | Yes | 156 | 18682380…18838423 |
|
LOC283755, POTE15 | 1 | ||||
Yes | 1067 | 18861808…19928521 | Yes | 572 | 18850029…19422452 | Yes | 344 | 18845990…19189673 |
|
OR4M2, OR4N4, LOC650137 | 1 | ||||||
Yes | 624 | 19207088…19835514 |
|
1 | |||||||||||||
26 | 15q25.3 | Yes | 161 | 83524791…83685356 | Yes | 228 | 83524791…83752853 | Yes | 228 | 83524791…83752450 |
|
AKAP12 | 0 | ||||
27 | 15q25.3 | Yes | 123 | 83784507…83907801 | Yes | 157 | 83784507…83941483 | Yes | 159 | 83790259…83949305 |
|
AKAP13 | 0 | ||||
28 | 16p11.2 | Yes | 118 | 31882658…32000323 | Yes | 1131 | 32531735…33662480 | Yes | 1377 | 32303108…33680554 |
|
LOC729355, TP53TG3 | 1 | ||||
Yes | 294 | 32088275…32382422 |
|
1 | |||||||||||||
Yes | 185 | 32538757…32723310 |
|
1 | |||||||||||||
Yes | 474 | 32962147…33436245 |
|
1 | |||||||||||||
Yes | 211 | 33451476…33662480 |
|
1 | |||||||||||||
29 | 17q21.31 | Yes | 586 | 41521621…42107467 | Yes | 198 | 41521621…41719935 | Yes | 586 | 41521621…42107467 | Yes | 407 | 41700624…42107467 |
|
KIAA1267, LRRC37A, ARL17, LRRC37A2, NSF | 1 | |
30 | 18p11.21 | Yes | 1545 | 15262486…16807594 | Yes | 130 | 15218647…15348836 |
|
ROCK1 | 1 | |||||||
31 | 19q13.31 | Yes | 116 | 47991257…48107552 | Yes | 133 | 47991257…48123857 | Yes | 235 | 47986218…48221228 |
|
PSG1, PSG6, PSG7, PSG11 | 1 | ||||
32 | 21p11.2 | Yes | 204 | 9758730…9962501 | Yes | 204 | 9758730…9962501 | Yes | 204 | 9758730…9962501 |
|
TPTE | 0 | ||||
33 | 22q11.22 | Yes | 148 | 21300127…21448190 | Yes | 200 | 21298324…21498767 | Yes | 178 | 21298324…21476564 |
|
GGTL4 | 0 | ||||
34 | Xp11.23 | Yes | 112 | 47917899…48029446 | Yes | 269 | 47917899…48186708 | Yes | 184 | 47917899…48102337 | Yes | 257 | 47935225…48192383 |
|
SSX5, SSX1, SSX9, SSX3 | 1 | |
35 | Xq13.1 | Yes | 185 | 71869375…72054837 | Yes | 185 | 71869375…72054837 |
|
|
DMRTC1 | 1 |
Identity of inherited CNVs found in Family 1 (7), Family 2 (8) and the gene regions which they overlap. Inherited CNVs are those which are present in either or both parents and transmitted to either or both twins. All size is in kb. SD indicates the percentage of overlap between segmental duplications and CNVs. ‘0’ means there is no overlap between CNV and segmental duplication, ‘1’ means 90–100% and ‘2’ means 50–90% overlap. Parental CNVs not transmitted to offspring were not included in
We also analyzed genes that overlapped
It is not surprising that genomic studies have begun to use monozygotic twins. In fact a number of them have identified copy number variations
In summary, the present study adds to the recent effort in human genetics to define the phenomenon of constancy and change using inheritance and origin of genome-wide CNVs and SNPs. The results demonstrate that CNVs often result from mitosis during early development facilitated by flanking repeats. They may lead to CNV differences among different tissue and make most individuals mosaics. The described approach expands the search for disease related genetic changes, indicates the time of their occurrence and begins to interrogate the mechanisms involved.
This research was approved by the Committee on Research Involving Human Subjects at the University of Western Ontario. The families and patients were identified, recruited and clinically assessed by Dr. Richard O'Reilly (Psychiatrist) and all participants (
Additional CNV analysis focused on two aspects. The first deals with identification of putative repeat elements in the flanking regions of CNVs; within a 1 kb region upstream and downstream of the CNV breakpoint which could promote breakage, deletion and duplication. The identification of repeat elements was carried out using repeat masker (
The use of Affymetrix 6.0 Human SNP array also allowed us to assess the transmission of a total of 909622 SNPs that are contained on the array. It allowed us to identify SNPs in the twins that were not present in either of the two parents; considered to be
We thank members of the two families who participated in this research.