A Map of Copy Number Variations in Chinese Populations

Abstract

It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ∼35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%), which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a useful resource in further evolutionary and medical studies.

Copy number variations and genetic admixtures in three Xinjiang ethnic minority groups

“…The quality control was the same as our previous study. 9 Samples which did not pass quality control were removed from subsequent analysis. We also removed the loci that showed difference (F ST 40) between combined calling results (all samples) and separate calling results (three ethnic groups).…”

“…We used an ExpectationMaximization algorithm to calculate the allele frequency by assuming that each CNV locus was in Hardy-Weinberg equilibrium, as in our previous study. 9 For each deletion or duplication allele in the admixed populations, the expected allele frequency was calculated as the sum of allele frequency of each ancestral source population weighted by its admixture proportion. Population differentiation for each CNV locus between each pair of populations was measured using the widely used pairwise F ST 13 based on the inferred allele frequency.…”

“…9 Based on the pair-wise distance among populations, we reconstructed the genetic relationship among these populations using Neighbor-joining method.…”

The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population

“…All probe coordinates in this study were mapped to human genome build GRCh37/hg19. We followed two different approaches for constructing a CNV map, which are: (1) so-called copy number variable region (CNVR) using any-overlap criterion 4,8,[11][12][13][16][17][18][20][21] and (2) copy number variable cytogenetic region (CNVcR) representing any cytogenetic region that contains one or more CNVs. The study protocol is shown in Supplementary Figure S1.…”

“…[8][9] Many such cohorts exhibited inter-and intra-population differences in CNV frequency distributions. [10][11][12][13][14][15][16][17][18][19][20][21][22] In addition to disease risk, these differences, furthermore, explain a significant proportion of normal phenotypic variation. [23][24][25][26] In this context, we characterized the genome-wide architecture of CNVs in 286 healthy, unrelated subjects characterized for musical aptitude and related traits.…”