Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology
DNA Mutational Analysis; *Gene Dosage; Gene Duplication; Gene Frequency; Genotype; Humans; Linkage Disequilibrium; Models, Genetic; *Polymorphism, Single Nucleotide; Sample Size
Bioinformatics | Computational Biology | Genetics and Genomics | Systems Biology
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.
Rights and Permissions
Copyright: 2008 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2008;3(12):e3906. doi: 10.1371/journal.pone.0003906. Epub 2008 Dec 18. Link to article on publisher's site
Lee, Soohyun; Kasif, Simon; Weng, Zhiping; and Cantor, Charles R., "Quantitative analysis of single nucleotide polymorphisms within copy number variation" (2008). Program in Bioinformatics and Integrative Biology Publications and Presentations. 39.