Open AccessNon-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle
Author(s) -
Akiko Takasuga,
Kunio Sato,
R. Nakamura,
Yosuke Saito,
Shinji Sasaki,
Takehito Tsuji,
Akio Suzuki,
Hiroshi Kobayashi,
Tomohiro Matsuhashi,
Koji Setoguchi,
Hiroshi Okabe,
Toshitake Ootsubo,
Ichiro Tabuchi,
Tatsuo Fujita,
Naoto Watanabe,
Takashi Hirano,
Syoyo Nishimura,
Toshio Watanabe,
Makio Hayakawa,
Yoshikazu Sugimoto,
Takatoshi Kojima
Publication year - 2015
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1005433
Subject(s) - biology , quantitative trait locus , short stature , genetics , dysplasia , allele , single nucleotide polymorphism , genotype , endocrinology , gene
Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia.