بهبود ارزیابی ژنومی گاوهای هلشتاین با استفاده از ماتریس روابط ژنومی بر پایه اطلاعات هاپلوتایپ ها

امروزه استفاده از اطلاعات هاپلوتایپ به منظور تخمین ارزش اصلاحی ژنومی (gebv) با صحت و دقت بالاتر مورد توجه قرار گرفته است. استفاده از شباهت بین هاپلوتایپ ها نسبت به مستقل در نظر گرفتن اثرات هاپلوتایپ ها می تواند منجر به قابلیت پیش گویی بالاتر برآوردهای ژنومی گردد. هدف از این مطالعه بررسی صحت و اریبی gebv به روش بهترین برآورد نااریب خطی ژنومی (gblup) با استفاده از ماتریس روابط خویشاوندی ژنومی بر پایه اطلاعات نشانگرهای چندشکلی تک نوکلئوتیدی (gsnp) و هاپلوتایپ (ghap) و ماتریس هیبرید شامل اطلاعات هاپلوتایپ ها وsnpها (gsnp,hap) بود. ماتریس های روابط خویشاوندی ژنومی با استفاده از تراشه k50 برای جمعیت گاو شیری هلشتاین آمریکای شمالی برای صفات تولید چربی شیر، تولید شیر، نمره سلول بدنی، تیپ و روزهای باز تشکیل گردید. مقادیر صحت gebv با استفاده از ماتریس gsnp و ghap به ترتیب از 0.49 (روزهای باز) تا 0.72 (تولید چربی شیر) و 0.50(روزهای باز) تا 0.73 (تولید چربی شیر) متغیر بود. استفاده از ماتریس ghap در مقایسه با دیگر ماتریس های مورد بررسی در این مطالعه منجر به برآوردهای نااریب تری در تمام صفات شد. استفاده از ماتریس ghap نسبت به gsnp موجب 6 تا 15 درصد کاهش اریبی برآوردها در صفات مختلف گردید. یکی از دلایل بهبود اریبی برآوردها می تواند برآورد بهتر واریانس ژنتیکی در سطح جمعیت توسط هاپلوتایپ نشانگرها نسبت به نشانگر انفرادی باشد. بر اساس نتایج حاضر ماتریس ghap می تواند جایگزین مناسبی برای gsnp در ارزیابی های ژنومی به منظور دستیابی به برآوردهای ارزش اصلاحی نااریب تر و دقیق تر باشد.

Improving Genomic Evaluation of Holstein Cattle Using a HaplotypeBased Relationship Matrix

Abstract Introduction With the advent of high throughput genotyping technologies, interest has grown in using genomic information to estimate breeding values. Genomic selection, in which genetic markers across the whole genome are used to estimate breeding values of individuals, is routinely applied in dairy cattle breeding programs. In dairy cattle, genomic selection has resulted in a substantial increase in the rate of genetic gain compared to traditional selection. This has been achieved mainly by reducing the generation interval, which became possible because of the higher accuracies of genomic breeding values (GEBV) estimated early in life compared to parent averages. Since single nucleotide polymorphism (SNP) genotypes are biallelic and, therefore, their information content is not high, so SNPbased methods may not effectively capture the linkage disequilibrium (LD) between SNPs and multiallelic quantitative trait loci (QTLs). Haplotypes are in general “multiallelic” and compared to individual SNPs may better capture LD with multiallelic QTL. Furthermore, most of the SNPs in the chips are old mutations. This may imply that SNPbased relationship matrix traces very old relationships from distant relatives and, therefore, may not trace changes due to recent selection accurately. It has also been hypothesized that using similarity between haplotypes to model the covariance between genomic effects can result in better predictive ability than modeling covariance based on SNP genotypes. So the objective of this study was to investigate the accuracy and bias of GEBV using genomic best linear unbiased prediction (GBLUP) with alternate genomic relationship matrices (G) based on SNPs and haplotypes information. Materials and Methods The North American Holstein genotype data was provided by the Canadian Dairy Network (CDN). The Holstein bulls with official domestic proofs were genotyped using the Illumina Bovine SNP 50 TM Chip. The genotyped Holstein bulls were classified as estimation group and prediction group. All bulls in prediction group were those bulls who were born from 2007 to 2011 and had official proof in 2015. Deregressed EBV (dEBV) based on the 2015 genetic evaluation (dEBV2015) were used for validation purposes. The estimation group included bulls born mainly between 1960 to 2007. The analyzed traits were fat yield, milk yield, somatic cell score, conformation, and days open. The GEBVs for mentioned traits were estimated based on GBLUP models using SNP1101 software. Three G matrices were built: 1) SNP genotype based relationship matrix (GSNP), 2) haplotype based relationship matrix (GHAP), and 3) hybrid matrix composing of SNP genotype and haplotype based relationship matrices (GSNP, HAP). Accuracy of prediction was calculated as Pearson’s correlation between estimated GEBV and dEBV2015 for prediction group. Bias of prediction was also calculated as regression coefficient of dEBV2015 on GEBV for prediction group. Results and Discussion Observed differences between alternate G matrices were larger in prediction bias than in prediction accuracy. Accuracy of genomic predictions based on GHAP were 0.73, 0.71, 0.62, 0.54, and 0.50 for fat yield, milk yield, somatic cell score, conformation, and days open, respectively. Accuracy of genomic predictions based on GSNP also were 0.72, 0.70, 0.61, 0.56, and 0.49, respectively. Although using GHAP instead of GSNP did not significantly improve the accuracy of prediction, it resulted in estimates with 6 (conformation) to 15% (days open) less bias and closer to one over the different traits. Genomic selection based on GHAP instead of GSNP seems to improve bias of prediction for traits under recent selection, such as days open. This might also be due to the fact that this trait is lowly heritable. Although accuracy of genomic predictions based on GSNP, HAP were similar to GSNP, using GSNP, HAP resulted in higher biases than GHAP or GSNP. Conclusion Based on these findings, GHAP might be an alternative approach to reduce bias of genomic predictions in routine genomic evaluations. Genomic selection based on GHAP instead of GSNP improved bias of prediction especially for low heritable traits under recent selection, such as days open. Small gain achieved with GHAP compared to GSNP may imply that the correlation between IBS and IBD in GHAP is not optimal for maximization of prediction accuracy. Based on current results further research is needed to investigate the use of haplotype length and allele frequency of markers in haplotype segments in the definition of haplotype similarity. In addition, this study suggests further research to assess the effect of recent selection, heritability and genetic architecture of the traits on the performance of haplotype based relationship matrix.