application of homozygosity haplotype analysis to genetic mapping with high-density snp genotype data应用纯合性单体型分析遗传与高密度snp基因型数据映射.pdfVIP

Application of Homozygosity Haplotype Analysis to Genetic Mapping with High-Density SNP Genotype Data 1 1,2 1,2 1,2,3 ´ 4 Haiyan Jiang *, Andrew Orr , Duane L. Guernsey , Johane Robitaille , Geraldine Asselin , Mark E. 5,6 ´4,5 Samuels , Marie-Pierre Dube 1 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada, 2 Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada, 3 Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada, 4 Montreal Heart Institute, Montreal, Quebec, Canada, 5 Department of ´ ´ Medicine, Universite de Montreal, Montreal, Quebec, Canada, 6 Centre de Recherche du CHU Ste-Justine, Montreal, Quebec, Canada Abstract Background: In families segregating a monogenic genetic disorder with a single disease gene introduction, patients share a mutation-carrying chromosomal interval with identity-by-descent (IBD). Such a shared chromosomal interval or haplotype, surrounding the actual pathogenic mutation, is typically detected and defined by multipoint linkage and phased haplotype analysis using microsatellite or SNP genotype data. High-density SNP genotype data presents a computational challenge for conventional genetic analyses. A novel non-parametric method termed Homozygosity Haplotype (HH) was recently proposed for the genome-wide search of the autosomal segments shared among patients using high density SNP genotype data. Methodology/Principal Findings: The applicability and the effectiveness of HH in identifying the potential linkage of disease causative gene with high-density SNP g