reducing the exome search space for mendelian diseases using genetic linkage analysis of exome genotypes减少对孟德尔疾病的外显子组搜索空间使用外显子组基因型的遗传连锁分析.pdfVIP

Smith et al. Genome Biology 2011, 12:R85 /2011/12/9/R85 METHOD Open Access Reducing the exome search space for Mendelian diseases using genetic linkage analysis of exome genotypes 1* 1 2 2,3 4,5 Katherine R Smith , Catherine J Bromhead , Michael S Hildebrand , A Eliot Shearer , Paul J Lockhart , 6 4,7,8 4 4,7 2,3,9 Hossein Najmabadi , Richard J Leventer , George McGillivray , David J Amor , Richard J Smith and Melanie Bahlo1,10 Abstract Many exome sequencing studies of Mendelian disorders fail to optimally exploit family information. Classical genetic linkage analysis is an effective method for eliminating a large fraction of the candidate causal variants discovered, even in small families that lack a unique linkage peak. We demonstrate that accurate genetic linkage mapping can be performed using SNP genotypes extracted from exome data, removing the need for separate array-based genotyping. We provide software to facilitate such analyses. Background genotypes obtained from genotyping arrays [16-18] or Whole exome sequencing (WES) has recently become a exome data [19,20]. This method does not incorporate popular strategy for discovering potential causal variants genetic map or allele frequency information, which in individuals with inherited Mendelian disorders, pro- could help to eliminate regions from consideration, and viding a cost- effective, fast-track approach to variant is applicable only to