Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies


Autoři: Jessica J. Hayward aff001;  Michelle E. White aff001;  Michael Boyle aff002;  Laura M. Shannon aff003;  Margret L. Casal aff004;  Marta G. Castelhano aff005;  Sharon A. Center aff005;  Vicki N. Meyers-Wallen aff001;  Kenneth W. Simpson aff005;  Nathan B. Sutter aff007;  Rory J. Todhunter aff005;  Adam R. Boyko aff001
Působiště autorů: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America aff001;  Cornell Center for Astrophysics and Planetary Science, Cornell University, Ithaca, New York, United States of America aff002;  Department of Horticultural Science, University of Minnesota, St Paul, Minnesota, United States of America aff003;  School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff004;  Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America aff005;  Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America aff006;  Biology Department, La Sierra University, Riverside, California, United States of America aff007
Vyšlo v časopise: Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008003
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008003

Souhrn

Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes.

Klíčová slova:

Biology and life sciences – Computational biology – Genome-wide association studies – Genetics – Genomics – Genome analysis – Animal genomics – Mammalian genomics – Human genetics – Genetic loci – Quantitative trait loci – Molecular genetics – Organisms – Eukaryota – Animals – Animal types – Pets and companion animals – Vertebrates – Amniotes – Mammals – Dogs – Zoology – Physiology – Physiological parameters – Molecular biology – Medicine and health sciences


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