Genome-wide association study using haplotype alleles for the evaluation of reproductive traits in Nelore cattle

<div><p>Zebu cattle (<i>Bos taurus indicus</i>) are highly adapted to tropical regions. However, females reach puberty after taurine heifers, which affects the economic efficiency of beef cattle breeding in the tropical regions. The aims of this study were to establish associations between the haplotype alleles of the bovine genome and age at first calving (AFC) in the Nelore cattle, and to identify the genes and quantitative trait loci (QTL) related to this phenotype. A total of 2,273 Nelore cattle (995 males and 1,278 females) genotyped using the Illumina BovineHD BeadChip were used in the current study. The association analysis included females with valid first calving records as well as open heifers. Linkage disequilibrium (LD) analysis among the markers was performed using blocks of 5, 10, and 15 markers, which were determined by sliding windows shifting one marker at a time. Then, the haplotype block size to be used in the association study was chosen based on the highest r² average among the SNPs in the block. The five HapAlleles most strongly associated with the trait (top five) were considered as significant associations. The results of the analysis revealed four genomic regions related to AFC, which overlapped with 20 QTL of the reproductive traits reported previously. Furthermore, there were 19 genes related to reproduction in those regions. In conclusion, the use of haplotypes allowed the detection of chromosomal regions associated with AFC in Nelore cattle, and provided the basis for elucidating the mechanisms underlying this trait.</p></div

Summary of the genes present in 1-MB windows centered on the haplotypes that were top five significant haplotype alleles.

<p>Summary of the genes present in 1-MB windows centered on the haplotypes that were top five significant haplotype alleles.</p

Manhattan plot of the genomic-wide association analysis of the –log₁₀ (p-value) of haplotype alleles and AFC trait.

<p>Each point in the graph represents a haplotype allele, arrows indicates de top five significant genomic regions and respective genes. The dashed line represent–log10(5 x 10⁻⁵) threshold.</p

Top five regions of the GWAS with haplotypic blocks, indicating the chromosomal localization (Chr), start and end positions, the respective SNPs, size and p-values.

<p>Top five regions of the GWAS with haplotypic blocks, indicating the chromosomal localization (Chr), start and end positions, the respective SNPs, size and p-values.</p

Detected major loci explaining variance in scrotal circumference in Nellore cattle.

a<p>MAF =  Minor allele frequency.</p>b<p> =  Average percentage of phenotypic variance explained by overlapping 1 Mb SNP windows.</p

Manhattan plots of scrotal circumference variance explained by SNP windows in Nellore cattle.

<p>Pseudo-phenotypes were based on dEBVs corrected for age (SC_A) and corrected for age and weight at yearling (SC_AW). Each dot represents a 1 Mb SNP window. Horizontal dashed lines represent adopted thresholds (SC_A = 0.40% and SC_Aw = 0.42%). Arrows indicate signals shared between the two models. Histograms represent the distribution of phenotypic variance explained by SNP windows, and the dotted vertical line marks the adopted thresholds.</p

Regional plots of scrotal circumference variance explained by SNP windows in Nellore cattle.

<p>Pseudo-phenotypes were based on dEBVs corrected for age (SC_A) and corrected for age and weight at yearling (SC_AW). Clear common signals between SC_A and SC_Aw were found on chromosomes A) 6, B) 10, C) 14 and D) 21. Vertical black dashed lines delimit the regions where the highest variance explained were found. Linkage disequilibrium structure for these regions (bottom) is portrayed as a heatmap of r² values between SNPs.</p

Descriptive statistics for scrotal circumference dEBVs of 861 Nellore bulls.

<p>Histograms (top), boxplot (bottom left) and normal quantile-quantile plots (bottom right) are provided for scrotal circumference A) corrected for age (SC_A) and B) corrected for age and weight at yearling (SC_AW). A scatter plot illustrating the linear relationship between the two dEBVs is also provided (C).</p