A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves
A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves
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DOI：
10.1111/age.12834
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发表时间：
2019-09-05
期刊：
影响因子：
2.4
通讯作者：
Wade, Claire
中科院分区：
文献类型：
--
作者：
Jagannathan, V;Droegemueller, C.;Wade, Claire
家犬是研究疾病遗传基础的极好模型。在狗身上发现了400多种类似人类疾病的遗传特征。为了进一步开展犬的医学遗传学研究，我们建立了犬生物医学变异数据库联盟（DBVDC），并提供了一个功能注释的基因组变异的全面列表，这些变异是通过对来自126个品种和8只狼的582只犬进行全基因组测序确定的。研究中使用的基因组的最小覆盖率为10倍，平均覆盖率接近24倍。总共，我们确定了23 133 692个单核苷酸变异（SNV）和10 048 038个短indel，包括93%的未描述的变异。平均而言，相对于参考基因组组装，每个单独的狗基因组携带类似于410万个单核苷酸和类似于140万个短插入缺失变体。约2%的变异位于注释基因和位点的编码区。变异效应分类结果显示，有247 141个SNV和99 562个短插入缺失对11 267个蛋白质编码基因有中度或高度影响。平均而言，每个基因组包含30个潜在胚胎致死基因和97个与发育障碍相关的基因的杂合功能丧失变体。使用DBVDC变体目录，已经揭示了50多种遗传性疾病和性状，使育种和诊断的基因检测成为可能。注释的变异及其相应的基因型频率的资源构成了一个非常有用的工具，用于识别潜在的变异致病罕见的遗传性疾病的狗。
The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have a minimum coverage of 10x and an average coverage of similar to 24x. In total, we identified 23 133 692 single-nucleotide variants (SNVs) and 10 048 038 short indels, including 93% undescribed variants. On average, each individual dog genome carried similar to 4.1 million single-nucleotide and similar to 1.4 million short-indel variants with respect to the reference genome assembly. About 2% of the variants were located in coding regions of annotated genes and loci. Variant effect classification showed 247 141 SNVs and 99 562 short indels having moderate or high impact on 11 267 protein-coding genes. On average, each genome contained heterozygous loss-of-function variants in 30 potentially embryonic lethal genes and 97 genes associated with developmental disorders. More than 50 inherited disorders and traits have been unravelled using the DBVDC variant catalogue, enabling genetic testing for breeding and diagnostics. This resource of annotated variants and their corresponding genotype frequencies constitutes a highly useful tool for the identification of potential variants causative for rare inherited disorders in dogs.