Genome-Wide Association Study Identifies Major Loci for Carcass Weight on BTA14 in Hanwoo (Korean Cattle)

<div><p>This genome-wide association study (GWAS) was conducted to identify major loci that are significantly associated with carcass weight, and their effects, in order to provide increased understanding of the genetic architecture of carcass weight in Hanwoo. This genome-wide association study identified one major chromosome region ranging from 23 Mb to 25 Mb on chromosome 14 as being associated with carcass weight in Hanwoo. Significant Bonferroni-corrected genome-wide associations (<i>P<1.52</i>×<i>10⁻⁶</i>) were detected for 6 Single Nucleotide Polymorphic (SNP) loci for carcass weight on chromosome 14. The most significant SNP was <i>BTB-01280026</i> (<i>P = 4.02×10⁻¹¹</i>), located in the 25 Mb region on Bos taurus autosome 14 (BTA14). The other 5 significant SNPs were <i>Hapmap27934-BTC-065223</i> (<i>P = 4.04×10⁻¹¹</i>) in 25.2 Mb, <i>BTB-01143580</i> (<i>P = 6.35×10⁻¹¹</i>) in 24.3 Mb, <i>Hapmap30932-BTC-011225</i> (<i>P = 5.92×10⁻¹⁰</i>) in 24.8 Mb, <i>Hapmap27112-BTC-063342</i> (<i>P = 5.18×10⁻⁹</i>) in 25.4 Mb, and <i>Hapmap24414-BTC-073009</i> (<i>P = 7.38×10⁻⁸</i>) in 25.4 Mb, all on BTA 14. One SNP (<i>BTB-01143580; P = 6.35×10⁻¹¹</i>) lies independently from the other 5 SNPs. The 5 SNPs that lie together showed a large Linkage disequilibrium (LD) block (block size of 553 kb) with LD coefficients ranging from 0.53 to 0.89 within the block. The most significant SNPs accounted for 6.73% to 10.55% of additive genetic variance, which is quite a large proportion of the total additive genetic variance. The most significant SNP (<i>BTB-01280026; P = 4.02×10⁻¹¹</i>) had 16.96 kg of allele substitution effect, and the second most significant SNP (<i>Hapmap27934-BTC-065223; P = 4.04×10⁻¹¹</i>) had 18.06 kg of effect on carcass weight, which correspond to 44% and 47%, respectively, of the phenotypic standard deviation for carcass weight in Hanwoo cattle. Our results demonstrated that carcass weight was affected by a major Quantitative Trait Locus (QTL) with a large effect and by many SNPs with small effects that are normally distributed.</p></div

Effect of the most significantly associated SNPs (<i>BTB_01143580</i> and <i>BTB_01280026</i>) on the carcass weight in the Hanwoo breed.

<p>The boxplots show the effects of the most significantly associated two SNPs and their haplotypes on the carcass weight.</p

Frequencies of favorable alleles of 6 SNP markers for carcass weight in the 1.1

<p>FA  =  favorable allele for carcass weight in Hanwoo (Korean brown cattle).</p><p>AG  =  Angus, BR  =  Brahman, HT  =  Holstein, HF  =  Hereford, LM  =  Limousine, KB  =  Korean brown Hanwoo, CHB  =  Korean Brindle Hanwoo, YBH  =  Chinese Yanbian cattle, CS  =  Chosun cattle and JBB  =  Jeju Black Hanwoo.</p

Reginal plot of the p values on chromosome 14 and candidate genes surrounding the six most significant SNPs.

<p>Significance (-log 10 of p-values) is plotted against position along the BTA14 and the 1.1 Mb region surrounding the six significant SNPs.</p

Trait means, standard deviations, variance components for the carcass traits, and number of animals in the Hanwoo discovery set.

<p>Trait means, standard deviations, variance components for the carcass traits, and number of animals in the Hanwoo discovery set.</p

The -logP value for the association between SNP and carcass weight on chromosome 14 (grey colour) and additive genetic variance (red colour) that significant SNPs (P<0.001) account for in single marker regression analysis.

<p>The -logP value for the association between SNP and carcass weight on chromosome 14 (grey colour) and additive genetic variance (red colour) that significant SNPs (P<0.001) account for in single marker regression analysis.</p

Association of 32,696 SNPs with the carcass weight in the Hanwoo breed.

<p>(A) Manhattan plot. Significance threshold was set up at P<1.5×10⁻⁶ (Bonferroni corrected significance level). (B) Quantile-quantile plot. The red line represents the 95% concentration band under the null hypothesis of no association. The black dot represent the P-values of the entire study, upper six dots represent SNPs with P<1×10⁻⁸ in this study.</p

SNPs showing significant association with carcass weight in 1,011 Hanwoo animals.

<p>Six SNPs meet the genome wide significance level of <i>P<1.52×10^-6</i>. The allelic substitution effect (β) is given for the minor allele in additive genetic effect derived from linear regression model of the carcass weight (kg). Positions are based on the Btau 4.1 assembly of the bovine genome sequence. The Vg indicates proportion of SNP vairance calculated from equation in material and methods.</p