气候变化领域集成服务门户(CCPortal): The impact of identity by descent on fitness and disease in dogs

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DOI	10.1073/pnas.2019116118
	The impact of identity by descent on fitness and disease in dogs
	Mooney J.A.; Yohannes A.; Lohmueller K.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Domestic dogs have experienced population bottlenecks, recent inbreeding, and strong artificial selection. These processes have simplified the genetic architecture of complex traits, allowed deleterious variation to persist, and increased both identity-by-descent (IBD) segments and runs of homozygosity (ROH). As such, dogs provide an excellent model for examining how these evolutionary processes influence disease. We assembled a dataset containing 4,414 breed dogs, 327 village dogs, and 380 wolves genotyped at 117,288 markers and data for clinical and morphological phenotypes. Breed dogs have an enrichment of IBD and ROH, relative to both village dogs and wolves, and we use these patterns to show that breed dogs have experienced differing severities of bottlenecks in their recent past. We then found that ROH burden is associated with phenotypes in breed dogs, such as lymphoma. We next test the prediction that breeds with greater ROH have more disease alleles reported in the Online Mendelian Inheritance in Animals (OMIA). Surprisingly, the number of causal variants identified correlates with the popularity of that breed rather than the ROH or IBD burden, suggesting an ascertainment bias in OMIA. Lastly, we use the distribution of ROH across the genome to identify genes with depletions of ROH as potential hotspots for inbreeding depression and find multiple exons where ROH are never observed. Our results suggest that inbreeding has played a large role in shaping genetic and phenotypic variation in dogs and that future work on understudied breeds may reveal new disease-causing variation. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Complex traits; Deleterious mutations; Fitness; Inbreeding depression
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179816
作者单位	Department of Human Genetics, University of California, Los Angeles, CA 90095, United States; Department of Biology, Stanford University, Stanford, CA 94305, United States; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, United States; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, United States
推荐引用方式 GB/T 7714	Mooney J.A.,Yohannes A.,Lohmueller K.E.. The impact of identity by descent on fitness and disease in dogs[J],2021,118(16).
APA	Mooney J.A.,Yohannes A.,&Lohmueller K.E..(2021).The impact of identity by descent on fitness and disease in dogs.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Mooney J.A.,et al."The impact of identity by descent on fitness and disease in dogs".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).