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固定长度单倍型可提高混种奶牛群体的基因组预测准确性。

Fixed-length haplotypes can improve genomic prediction accuracy in an admixed dairy cattle population.

作者信息

Hess Melanie, Druet Tom, Hess Andrew, Garrick Dorian

机构信息

Iowa State University, Ames, IA, USA.

LIC, Hamilton, New Zealand.

出版信息

Genet Sel Evol. 2017 Jul 3;49(1):54. doi: 10.1186/s12711-017-0329-y.

Abstract

BACKGROUND

Fitting covariates representing the number of haplotype alleles rather than single nucleotide polymorphism (SNP) alleles may increase genomic prediction accuracy if linkage disequilibrium between quantitative trait loci and SNPs is inadequate. The objectives of this study were to evaluate the accuracy, bias and computation time of Bayesian genomic prediction methods that fit fixed-length haplotypes or SNPs. Genotypes at 37,740 SNPs that were common to Illumina BovineSNP50 and high-density panels were phased for ~58,000 New Zealand dairy cattle. Females born before 1 June 2008 were used for training, and genomic predictions for milk fat yield (n = 24,823), liveweight (n = 13,283) and somatic cell score (n = 24,864) were validated within breed (predominantly Holstein-Friesian, predominantly Jersey, or admixed KiwiCross) in later-born females. Covariates for haplotype alleles of five lengths (125, 250, 500 kb, 1 or 2 Mb) were generated and rare haplotypes were removed at four thresholds (1, 2, 5 or 10%), resulting in 20 scenarios tested. Genomic predictions fitting covariates for either SNPs or haplotypes were calculated by using BayesA, BayesB or BayesN. This is the first study to quantify the accuracy of genomic prediction using haplotypes across the whole genome in an admixed population.

RESULTS

A correlation of 0.349 ± 0.016 between yield deviation and genomic breeding values was obtained for milk fat yield in Holstein-Friesians using BayesA fitting covariates. Genomic predictions were more accurate with short haplotypes than with SNPs but less accurate with longer haplotypes than with SNPs. Fitting only the most frequent haplotype alleles reduced computation time with little decrease in prediction accuracy for short haplotypes. Trends were similar for all traits and breeds and there was little difference between Bayesian methods.

CONCLUSIONS

Fitting covariates for haplotype alleles rather than SNPs can increase prediction accuracy, although it decreased drastically for long (>500 kb) haplotypes. In this population, fitting 250 kb haplotypes with a 1% frequency threshold resulted in the highest genomic prediction accuracy and fitting 125 kb haplotypes with a 10% frequency threshold improved genomic prediction accuracy with comparable computation time to fitting SNPs. This increased accuracy is likely to increase genetic gain by changing the ranking of selection candidates.

摘要

背景

如果数量性状基因座与单核苷酸多态性(SNP)等位基因之间的连锁不平衡不足,拟合代表单倍型等位基因数量而非SNP等位基因的协变量可能会提高基因组预测准确性。本研究的目的是评估拟合固定长度单倍型或SNP的贝叶斯基因组预测方法的准确性、偏差和计算时间。对Illumina BovineSNP50和高密度面板共有的37740个SNP位点的基因型进行了分型,涉及约58000头新西兰奶牛。2008年6月1日前出生的雌性奶牛用于训练,对乳脂产量(n = 24823)、活重(n = 13283)和体细胞评分(n = 24864)的基因组预测在后代雌性奶牛的品种内(主要是荷斯坦-弗里生牛、主要是泽西牛或混合的奇异杂交牛)进行了验证。生成了五种长度(125、250、500 kb、1或2 Mb)的单倍型等位基因的协变量,并在四个阈值(1%、2%、5%或10%)下去除了罕见单倍型,共测试了20种情况。使用BayesA、BayesB或BayesN计算拟合SNP或单倍型协变量的基因组预测。这是第一项在混合群体中量化全基因组使用单倍型进行基因组预测准确性的研究。

结果

使用BayesA拟合协变量时,荷斯坦-弗里生牛的乳脂产量的产量偏差与基因组育种值之间的相关性为0.349±0.016。短单倍型的基因组预测比SNP更准确,但长单倍型的基因组预测比SNP更不准确。仅拟合最常见的单倍型等位基因可减少计算时间,而短单倍型的预测准确性几乎没有下降。所有性状和品种的趋势相似,贝叶斯方法之间差异不大。

结论

拟合单倍型等位基因的协变量而非SNP可以提高预测准确性,尽管长(>500 kb)单倍型的预测准确性大幅下降。在这个群体中,拟合频率阈值为1%的250 kb单倍型导致最高的基因组预测准确性,拟合频率阈值为10%的125 kb单倍型提高了基因组预测准确性,且计算时间与拟合SNP相当。这种提高的准确性可能会通过改变选择候选个体的排名来增加遗传增益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd26/5494768/ed5228a6f933/12711_2017_329_Fig1_HTML.jpg

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