Fig 1.
Strategy for epidemiological research on Mendelian disorder using exome sequences.
A flow chart used to study the geographic prevalence shows the process of mutation detection using 1000G and NHLBI datasets. A total of 15,190 haploid exomes were screened for 161 causative mutations linked to 18 genetic disorders. Several platforms (NCBI dbSNP and UCSC Browser) were used to access the validity of mutations and examine previous information on gene annotations and alleles.
Table 1.
Estimated carrier rates of 15 Mendelian disorders by race, ethnicity, and country.
The information about the mutation and carrier rate is shown in this figure. Pustular psoriasis caused by is yet described in OMIM. The abbreviations are as follows: AA, African Americans; EA, European Americans; ASW, American’s of African Ancestry in SW; CEU, Utah Residents (CEPH) with Northern and Western European ancestry; CHB, Han Chinese in Beijing; CHS, Southern Han Chinese; CLM, Colombian from Medellin; FIN, Finnish in Finland; GBR, British in England; IBS, Iberian population in Spain; JPT, Japanese in Tokyo; LWK, Luhya in Webuye; MXL, Mexican ancestry from Los Angeles; PUR, Puerto Rico from Puerto Rica; TSI, Toscani in Italia; YRI, Yoruba in Ibadan.
Fig 2.
Geographical minor allele frequency distribution for the causative mutations of representative three Mendelian disorders.
Pie areas are proportional to the minor allele frequency of the causative mutations for three inherited diseases (A: SCA, B: Pustular psoriasis, C: Miller syndrome). 1000G and NHLBI (2 + 14) populations are displayed separately. The thick white circle indicates the absence (0%) of mutations in the population. The right bar chart shows the mutation minor allele frequency in each population. A world map was obtained from Free Editable Worldmap (http://free-editable-worldmap-for-powerpoint.en.softonic.com/) and modified.
Table 2.
Comparison of predicted exome-based carrier rates with previous clinical estimates.
The P-value is calculated from Chi-square tests between two carrier estimates.
Table 3.
Estimated carrier rates of 17 Mendelian disorders using ExAC data.
The carrier rates of Mendelian disorders were estimated using ExAC dataset. Child-hood cardiomyopathy (MIM no description) and Usher syndrome type 1J (USH1J) (#614869) were detected in ExAC but not in 1000G and NHLBI. ExAC populations are largely divided into six races: African, Latino, European (non-Finnish), European (Finnish), South Asian, East Asian, and Other.
Fig 3.
Risk simulation and mutation detection rate of autosomal recessive disease.
The simulation graph depicts the theoretical mutation detection probability of high-penetrance genetic mutations (under the condition of σ = 0.01) that are associated with inherited disorders. The simulation sample sizes range from 1 to 100,000. The y-axis corresponds to the detection rate of causative mutations.