Association of TMEM8B and SPAG8 with Mature Weight in Sheep

SIMPLE SUMMARY: Domestication and the subsequent selection of animals for either economic or morphological features can impact the legacy genome of a population in myriad ways. In sheep, the rs426272889 single nucleotide polymorphism (SNP) was identified as the peak of a signature of selection. We examined phenotypic data and identified associations for the Transmembrane protein 8B (TMEM8B) rs426272889 SNP and its genetically linked Sperm-associated antigen 8 (SPAG8) rs160159557 SNP with ewe mature weight in four sheep breeds. These data provided the first production-relevant phenotypes, as well as the first organism-level (as opposed to cellular or tumor-derived) phenotypes, associated with TMEM8B, and in so doing, improved the annotation of this gene and genomic region by adding body weight implications. Once validated, these data can be applied in genetic or genomic selection aiming to achieve desired mature body weight. ABSTRACT: Signature of selection studies have identified many genomic regions with known functional importance and some without verified functional roles. Multiple studies have identified Transmembrane protein 8B (TMEM8B) rs426272889 as having been recently under extreme selection pressure in domesticated sheep, but no study has provided sheep phenotypic data clarifying a reason for extreme selection. We tested rs426272889 for production trait association in 770 U.S. Rambouillet, Targhee, Polypay, and Suffolk sheep. TMEM8B rs426272889 was associated with mature weight at 3 and 4 years (p < 0.05). This suggested selection for sheep growth and body size might explain the historical extreme selection pressure in this genomic region. We also tested Sperm-associated antigen 8 (SPAG8) rs160159557 encoding a G493C substitution. While this variant was associated with mature weights at ages 3 and 4, it was not as strongly associated as TMEM8B rs426272889. Transmembrane protein 8B has little functional information except as an inhibitor of cancer cell proliferation. To our knowledge, this is the first study linking TMEM8B to whole organism growth and body size under standard conditions. Additional work will be necessary to identify the underlying functional variant(s). Once identified, such variants could be used to improve sheep production through selective breeding.