RT Journal Article
SR Electronic
T1 Genome wide association analysis uncovers variants for reproductive variation across dog breeds and links to domestication
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 285791
DO 10.1101/285791
A1 Samuel P. Smith
A1 Julie B. Phillips
A1 Maddison L. Johnson
A1 Patrick Abbot
A1 John A. Capra
A1 Antonis Rokas
YR 2018
UL http://biorxiv.org/content/early/2018/12/18/285791.abstract
AB 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, Canis lupus familiaris 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. 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 co-variates. We identified 13 genome-wide significant associations between these traits and genetic loci, including variants near CACNA2D3 with gestation length, MSRB3 and KRT71 with litter size, SM0C2 with cesarean section rate, and HTR2C with stillbirth rate. Some of these loci, such as CACNA2D3 and MSRB3, have been previously implicated in human reproductive pathologies, whereas others have been previously associated with domestication-related traits, including brachycephaly (SM0C2), coat curl (KRT71), and tameness (HTR2C). These results raise the hypothesis that the artificial selection that gave rise to dog breeds also shaped 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 Variation in reproductive traits across mammals has been extensively investigated and is well established, but the genetic contributors to this variation remain largely unknown. Here, we take advantage of the domestic dog, a powerful model for mammalian genetics, to gain insight into the genetic basis of reproductive traits. By examining the association between more than a hundred thousand genetic variants and four reproductive traits that vary extensively across dog breeds, we identified more than a dozen significant associations for cesarean section rate, litter size, stillbirth rate, and gestation length. Some of the variants that we identify are nearby genes previously implicated in human reproductive pathologies, whereas several others have been previously associated with domestication-related traits. Our results establish the domestic dog as a tractable system for studying the genetics of reproductive traits and underscore the potential for cryptic interactions between reproductive and other traits favored over the course of adaptation.