title: Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.
abstract: The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation.
authors.affiliation: College of Veterinary Medicine, Texas A&M University Interdisciplinary Program in Genetics, Texas A&M University.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Davis
authors.affiliation: College of Veterinary Medicine, Texas A&M University Interdisciplinary Program in Genetics, Texas A&M University.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Seabury
authors.affiliation: College of Veterinary Medicine, Texas A&M University Interdisciplinary Program in Genetics, Texas A&M University.
authors.forename: Wesley A
authors.initials: WA
authors.lastname: Brashear
authors.affiliation: College of Veterinary Medicine, Texas A&M University.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Texas A&M University National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Melody
authors.initials: M
authors.lastname: Roelke-Parker
authors.affiliation: College of Veterinary Medicine, Texas A&M University Interdisciplinary Program in Genetics, Texas A&M University wmurphy@cvm.tamu.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001947:Breeding; D002415:Cats; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D016678:Genome; D055106:Genome-Wide Association Study; D006824:Hybridization, Genetic; D007246:Infertility / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D017423:Sequence Analysis, RNA; D014960:X Chromosome / Q000235:genetics
keywords: Haldane's rule; feline; hybrid sterility; large X-effect; speciation