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.

Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle

“…Previous studies have reported that some disease-associated alleles are accompanied by a favorable effect on other economic traits in cattle [27–29]. Meat from Japanese Black cattle is highly valued for its abundant marbling due to considerable intramuscular fat deposition [30, 31].…”

Genome‐wide association study for carcass traits, fatty acid composition, chemical composition, sugar, and the effects of related candidate genes in Japanese Black cattle

“…), and FYVE, RhoGEF and PH domain‐containing protein 3 ( FGD3 ; Takasuga et al . ). Regarding fatty acid composition, fatty acid synthase ( FASN ; Abe et al .…”

Genetic Variants in SDC3 Gene are Significantly Associated with Growth Traits in Two Chinese Beef Cattle Breeds

“…Because all syndecans have a common structure, according to the three different structural domains of SDC3, the site where the missense mutation occurred probably located in a large extracellular domain. The functional significance of this substitution is unknown, but we presumed this missense mutation may change the amino acid property and affect the encoded protein structure (31) As a result, numerous current studies on animal genomics are focused on the analysis of mutations located within economically important genes that could correspond to previously described quantitative trait loci (QTL) (32)(33)(34).…”

“…Numerous studies in the past few decades have clearly shown that synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the expression and function of the protein in which they occur (32)(33)(34)(35). However, according to recent research, the synonymous SNPs can affect protein expression by alteration or increase in the stability of the mRNA (38)(39)(40)(41).…”