The 81st Annual Meeting of the American Association of Physical Anthropologists (2012)

The extent of rare, population specific genomic copy number variation: Implications for indigenous human populations


Pathology, Harvard Medical School/Brigham and Women’s Hospital

Thursday 8:45-9:00, Galleria North Add to calendar

Copy number variants (CNVs) are DNA segments that vary in copy number among individuals and are surprisingly widespread in the genomes of phenotypically normal humans. In addition, CNVs functionally affect expression levels, susceptibility to certain common diseases, and intriguingly, local adaptations. Hence, CNVs may constitute a major portion of the genomic variation that contributes to heritable phenotypic variation among humans. Recently, several studies attempted high-resolution and comprehensive discovery of copy number variants among continental populations (e.g., Yoruba, representing African populations, and Caucasians from Utah (CEU) representing European populations), and found an excess of rare and singleton CNVs when compared to other types of genomic variants, such as single nucleotide polymorphisms (SNPs). For instance, in one recent study, we sequenced the genomes of 8 self-identified Koreans and uncovered 3,346 deletion CNVs mapped at nucleotide resolution. We revealed that more than 75% of these variants are population specific. In our preliminary analysis of the existing CNV data, we provide evidence that high de novo CNV formation rates, coupled with higher rates of purifying selection, contribute to the high rates of population-specific CNVs among humans. We further extrapolated our estimation to indigenous populations with different sizes and demographic histories. Taken together, we provide evidence that there is ample incentive for undertaking focused studies with well-contextualized sampling from local populations in order to discover population-specific variants that have had a phenotypic impact on extant human groups.

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