Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation
Date
2008-12-18
Authors
Lee, Soohyun
Kasif, Simon
Weng, Zhiping
Cantor, Charles R.
Version
OA Version
Citation
Lee, Soohyun, Simon Kasif, Zhiping Weng, Charles R. Cantor. "Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation" PLoS ONE 3(12): e3906. (2008)
Abstract
BACKGROUND. Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. RESULTS. We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. CONCLUSIONS. Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.