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.

Akiko Takasuga,Tatsuo Fujita,Akio Suzuki,Naoto Watanabe,Toshitake Ootsubo,Takashi Hirano,Takehito Tsuji,Hiroshi Okabe,Toshio Watanabe,Yosuke Saito,Yoshikazu Sugimoto,Kunio Sato,Takatoshi Kojima,Hiroshi Kobayashi,Ichiro Tabuchi,Makio Hayakawa,Koji Setoguchi,Shinji Sasaki,R Nakamura ,Syoyo Nishimura ,Tomohiro Matsuhashi

doi:10.1371/journal.pgen.1005433

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.

Highlights

Carcass weight, as a measure of meat yield, is an economically important trait in livestock
The carcass weight quantitative trait locus (QTL), named CW-3, was previously identified as one of three major QTL in Japanese Black cattle, and it was found to originate from a specific line that had been maintained in a regional subpopulation
Half-sib QTL analyses of the elite sires repeatedly detected the CW-3 QTL, while skeletal dysplasia has been found in the descendants

Summary

Introduction

As a measure of meat yield, is an economically important trait in livestock. Due to its economic significance, several quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS) have been conducted with the objective of identifying genes for improving meat production. These studies reveal that body length or stature is often times directly related to meat yield [1,2,3]. Two loci, named CW-1 and CW-2, correspond to PLAG1 [7] and NCAPG-LCORL [2], respectively, both of which have been identified as loci influencing adult human height [8,9,10] and associated with body size-related traits in different cattle breeds and other livestock species (reviewed in [11]). The third locus, named CW-3, showed the largest allele substitution effect (+35.0 kg) among the three loci, while the Q allele frequency was the lowest (11.5%) and detected in a specific line of Japanese Black cattle [7]

Methods

Results

Discussion

Conclusion