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Identity-by-descent filtering of exome sequence data for disease–gene identification in autosomal recessive disorders

机译:外显子序列数据的后裔身份过滤用于常染色体隐性遗传疾病的疾病基因鉴定

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摘要

>Motivation: Next-generation sequencing and exome-capture technologies are currently revolutionizing the way geneticists screen for disease-causing mutations in rare Mendelian disorders. However, the identification of causal mutations is challenging due to the sheer number of variants that are identified in individual exomes. Although databases such as dbSNP or HapMap can be used to reduce the plethora of candidate genes by filtering out common variants, the remaining set of genes still remains on the order of dozens.>Results: Our algorithm uses a non-homogeneous hidden Markov model that employs local recombination rates to identify chromosomal regions that are identical by descent (IBD = 2) in children of consanguineous or non-consanguineous parents solely based on genotype data of siblings derived from high-throughput sequencing platforms. Using simulated and real exome sequence data, we show that our algorithm is able to reduce the search space for the causative disease gene to a fifth or a tenth of the entire exome.>Availability: An R script and an accompanying tutorial are available at .>Contact:
机译:>动机:下一代测序和外显子组捕获技术目前正在改变遗传学家筛查罕见孟德尔疾病中致病突变的方式。但是,由于在单个外显子组中识别出的变体数量众多,因此确定因果突变是一项挑战。尽管可以使用诸如dbSNP或HapMap之类的数据库通过过滤掉常见变体来减少过多的候选基因,但是其余的基因组仍然保持在数十种左右。>结果:我们的算法使用的是非-均质的隐马尔可夫模型,该模型仅使用源自高通量测序平台的同胞的基因型数据,采用局部重组率来鉴定血缘或非血缘父母子女的血统相同的染色体区域(IBD = 2)。使用模拟的和实际的外显子组序列数据,我们证明了我们的算法能够将导致疾病的基因的搜索空间减少到整个外显子组的五分之一或十分之一。>可用性:随附的教程可从以下网站获得。>联系方式:

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