John Capra
Last active: 3/3/2020

Genome-wide association analysis uncovers variants for reproductive variation across dog breeds and links to domestication.

Smith SP, Phillips JB, Johnson ML, Abbot P, Capra JA, Rokas A
Evol Med Public Health. 2019 2019 (1): 93-103

PMID: 31263560 · PMCID: PMC6592264 · DOI:10.1093/emph/eoz015

Background and objectives - The diversity of eutherian reproductive strategies has led to variation in many traits, such as number of offspring, age of reproductive maturity and gestation length. While reproductive trait variation has been extensively investigated and is well established in mammals, the genetic loci contributing to this variation remain largely unknown. The domestic dog, is a powerful model for studies of the genetics of inherited disease due to its unique history of domestication. To gain insight into the genetic basis of reproductive traits across domestic dog breeds, we collected phenotypic data for four traits, cesarean section rate, litter size, stillbirth rate and gestation length, from primary literature and breeders' handbooks.

Methodology - By matching our phenotypic data to genomic data from the Cornell Veterinary Biobank, we performed genome-wide association analyses for these four reproductive traits, using body mass and kinship among breeds as covariates.

Results - We identified 12 genome-wide significant associations between these traits and genetic loci, including variants near with gestation length, and with litter size, with cesarean section rate and with stillbirth rate. A few of these loci, such as and , have been previously implicated in human reproductive pathologies, whereas others have been associated with domestication-related traits, including brachycephaly () and coat curl ().

Conclusions and implications - We hypothesize that the artificial selection that gave rise to dog breeds also influenced the observed variation in their reproductive traits. Overall, our work establishes the domestic dog as a system for studying the genetics of reproductive biology and disease.

LAY SUMMARY - The genetic contributors to variation in mammalian reproductive traits remain largely unknown. We took advantage of the domestic dog, a powerful model system, to test for associations between genome-wide variants and four reproductive traits (cesarean section rate, litter size, stillbirth rate and gestation length) that vary extensively across breeds. We identified associations at a dozen loci, including ones previously associated with domestication-related traits, suggesting that selection on dog breeds also influenced their reproductive traits.

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