Abstract:
:Copy number variants (CNVs) contribute to human genetic and phenotypic diversity. However, the distribution of larger CNVs in the general population remains largely unexplored. We identify large variants in approximately 2500 individuals by using Illumina SNP data, with an emphasis on "hotspots" prone to recurrent mutations. We find variants larger than 500 kb in 5%-10% of individuals and variants greater than 1 Mb in 1%-2%. In contrast to previous studies, we find limited evidence for stratification of CNVs in geographically distinct human populations. Importantly, our sample size permits a robust distinction between truly rare and polymorphic but low-frequency copy number variation. We find that a significant fraction of individual CNVs larger than 100 kb are rare and that both gene density and size are strongly anticorrelated with allele frequency. Thus, although large CNVs commonly exist in normal individuals, which suggests that size alone can not be used as a predictor of pathogenicity, such variation is generally deleterious. Considering these observations, we combine our data with published CNVs from more than 12,000 individuals contrasting control and neurological disease collections. This analysis identifies known disease loci and highlights additional CNVs (e.g., 3q29, 16p12, and 15q25.2) for further investigation. This study provides one of the first analyses of large, rare (0.1%-1%) CNVs in the general population, with insights relevant to future analyses of genetic disease.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Itsara A,Cooper GM,Baker C,Girirajan S,Li J,Absher D,Krauss RM,Myers RM,Ridker PM,Chasman DI,Mefford H,Ying P,Nickerson DA,Eichler EEdoi
10.1016/j.ajhg.2008.12.014subject
Has Abstractpub_date
2009-02-01 00:00:00pages
148-61issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(09)00002-0journal_volume
84pub_type
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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