title: Genome-Wide Association Mapping for Female Infertility in Inbred Mice.
abstract: The genetic factors underlying female infertility in humans are only partially understood. Here, we performed a genome-wide association study of female infertility in 25 inbred mouse strains by using publicly available SNP data. As a result, a total of four SNPs were identified after chromosome-wise multiple test correction. The first SNP rs29972765 is located in a gene desert on chromosome 18, about 72 kb upstream of Skor2 (SKI family transcriptional corepressor 2). The second SNP rs30415957 resides in the intron of Plce1 (phospholipase C epsilon 1). The remaining two SNPs (rs30768258 and rs31216810) are close to each other on chromosome 19, in the vicinity of Sorbs1 (sorbin and SH3 domain containing 1). Using quantitative RT-PCR, we found that Sorbs1 is highly expressed in the mouse uterus during embryo implantation. Knockdown of Sorbs1 by siRNA attenuates the induction of differentiation marker gene Prl8a2 (decidual prolactin-related protein) in an in vitro model of decidualization using mouse endometrial stromal cells, suggesting that Sorbs1 may be a potential candidate gene for female infertility in mice. Our results may represent an opportunity to further understand female infertility in humans.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China jilongliu@scau.edu.cn.
authors.forename: Ji-Long
authors.identifier: 0000-0002-6948-2576
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Department of Biology, Shantou University, Shantou 515063, China.
authors.forename: Tong-Song
authors.initials: TS
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002874:Chromosome Mapping; D003656:Decidua / Q000378:metabolism / Q000473:pathology; D010064:Embryo Implantation / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000473:pathology; D007438:Introns / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000235:genetics*; D014599:Uterus / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C119201:ponsin; D011388:Prolactin; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: Decidualization; Female infertility; Genome-wide association mapping; Inbred mice