quantitative analysis of single nucleotide polymorphisms within copy number variation定量分析的单核苷酸多态性在拷贝数变异.pdfVIP

Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation 1 1,2,3 1,2,5 1,2,4 Soohyun Lee , Simon Kasif , Zhiping Weng *, Charles R. Cantor * 1 Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America, 2 Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America, 3 Children’s Hospital Informatics Program at Harvard-MIT Health Sciences and Technology, Boston, Massachusetts, United States of America, 4 Sequenom Inc., San Diego, California, United States of America, 5 Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, Massachusetts, United States of America 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