title: Non-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.
abstract: 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.
authors: National Livestock Breeding Center, Odakura, Nishigo, Fukushima, Japan; Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Akiko
authors: A
authors: Takasuga
authors: Oita Prefectural Agriculture, Forestry and Fisheries Research Center, Kuju, Takeda, Oita, Japan.
authors: Kunio
authors: K
authors: Sato
authors: Shimane Prefectural Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors: Ryouichi
authors: R
authors: Nakamura
authors: Miyagi Prefectural Livestock Experiment Station, Iwadeyama, Osaki, Miyagi, Japan.
authors: Yosuke
authors: Y
authors: Saito
authors: National Livestock Breeding Center, Odakura, Nishigo, Fukushima, Japan; Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Shinji
authors: S
authors: Sasaki
authors: Graduate School of Environmental and Life Science, Okayama University, Tsushima-naka, Okayama, Japan.
authors: Takehito
authors: T
authors: Tsuji
authors: Aomori Prefectural Industrial Technology Research Center, Moritatukimino, Morita, Tugaru, Aomori, Japan.
authors: Akio
authors: A
authors: Suzuki
authors: Okayama Prefectural Research Institute of Livestock Industry, Misaki, Kume, Okayama, Japan.
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Gifu Prefectural Livestock Research Institute, Kiyomi, Takayama, Gifu, Japan.
authors: Tamako
authors: T
authors: Matsuhashi
authors: Cattle Breeding Development Institute of Kagoshima Prefecture, Osumi, So, Kagoshima, Japan.
authors: Koji
authors: K
authors: Setoguchi
authors: Nagasaki Prefectural Beef Cattle Improvement Center, Tabiracho Kotedamen, Hirado, Nagasaki, Japan.
authors: Hiroshi
authors: H
authors: Okabe
authors: Saga Prefectural Livestock Experiment Station, Yamauchi, Takeo, Saga, Japan.
authors: Toshitake
authors: T
authors: Ootsubo
authors: Tottori Animal Husbandry Experiment Station, Kotoura, Touhaku, Tottori, Japan.
authors: Ichiro
authors: I
authors: Tabuchi
authors: Oita Prefectural Agriculture, Forestry and Fisheries Research Center, Kuju, Takeda, Oita, Japan.
authors: Tatsuo
authors: T
authors: Fujita
authors: Oita Prefectural Agriculture, Forestry and Fisheries Research Center, Kuju, Takeda, Oita, Japan.
authors: Naoto
authors: N
authors: Watanabe
authors: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Takashi
authors: T
authors: Hirano
authors: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Shota
authors: S
authors: Nishimura
authors: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Toshio
authors: T
authors: Watanabe
authors: School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan.
authors: Makio
authors: M
authors: Hayakawa
authors: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors: Yoshikazu
authors: Y
authors: Sugimoto
authors: National Livestock Breeding Center, Odakura, Nishigo, Fukushima, Japan.
authors: Takatoshi
authors: T
authors: Kojima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001827:Body Height / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000662:veterinary*; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006132:Growth Plate / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D040641:Quantitative Trait Loci; D012306:Risk
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D017027:Protein Tyrosine Phosphatases