Scientia Agricultura Sinica ›› 2024, Vol. 57 ›› Issue (11): 2243-2253.doi: 10.3864/j.issn.0578-1752.2024.11.015

• ANIMAL SCIENCE·VETERINARY SCIENCE • Previous Articles     Next Articles

The Efficiency of Haplotype-Based Genomic Selection Using Genotyping by Target Sequencing in Pigs

LIU YanLing1(), QIU Ao1(), ZHANG ZiPeng1, WANG Xue1, DU HeHe1, LUO WenXue2, WANG GuiJiang2, WEI Xia3, SHI WenYing3, DING XiangDong1()   

  1. 1 College of Animal Science and Technology, China Agricultural University/National Engineering Laboratory of Animal Breeding/ Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Beijing 100193
    2 Hebei Animal Husbandry Extension Station, Shijiazhuang 050061
    3 Zhangjiakou Dahaoheshan New Agricultural Development Co., Ltd., Zhangjiakou 076250, Hebei
  • Received:2023-12-12 Accepted:2024-03-01 Online:2024-06-01 Published:2024-06-07
  • Contact: DING XiangDong

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Abstract:

【Objective】This study explored the efficiency of haplotype-based genomic selection using genotyping by target sequencing technology in order to provide the useful experience for molecular breeding of pigs in China.【Method】The growth traits records of 1 267 Large White pigs and the reproduction trait records of 800 Large White pigs were collected and genotyped by using the porcine 50K liquid-phase SNP panel (liquid-phase 50K) based on the Genotyping by Target Sequencing (GBTS) as well as its target resequencing data. Three strategies for haplotype block partition, including fixed SNP number, fixed length, and target block, were proposed to construct haplotypes, and the corresponding haplotype-based genomic prediction were compared with single SNP genomic prediction. The target block partition strategy was mainly based on target resequencing data obtained by the GBTS, and one haplotype block contained one target site in liquid-phase 50K and its upstream and downstream SNPs (mSNP) within 400 bp from target resequencing data. In this study, after phasing haplotype using Beagle 5.1 within each haplotype block, the different haplotypes were recoded as haplotype alleles, and then haplotype allele matrix was constructed using haplotype dosage model. A single-step GBLUP model (ssGBLUP) was then used to estimate genomic breeding values for three traits of days at 100 kg body weight (AGE), backfat thickness at 100 kg (BF), and total number of born (TNB). A two-trait animal model was implemented for two growth traits of AGE and BF, and repeatability model for TNB. Younger validation population and five-fold cross validation were carried out to assess the efficiency of genomic prediction. The correlation coefficients between estimated breeding values and genomic estimated breeding values were measured as the accuracy of genomic prediction, and the regression coefficients of genomic estimated breeding values on estimated breeding values were measured unbiasedness, respectively.【Result】The results from the younger validation population showed that the target resequencing data yielded lower accuracies of genomic selection on three traits than liquid-phase 50K SNP, even its number of SNP after genotype quality control was increased from 42 302 in liquid phase 50K to 88 105. The haplotype blocks partitioned by target block strategy contained 2.08 SNPs and 5.67 haplotype alleles on average. The accuracies of haplotype-based genomic selection based on all three haplotype block partition strategies were improved, and the target block gained the largest improvement, yielding 4.80%, 1.98% and 6.04% higher accuracies on AGE, BF and TNB than liquid- phase 50K, respectively. In addition, the target block strategy generated the lowest bias in most scenarios as well. The five-fold cross-validation obtained similar results as younger validation population did, target block gained advantages over both single SNP and other haplotype block partition methods. The fixed length of 400 bp block partition strategy performed comparable with target block, while it was time demanding. Although fixed 2 and 5 SNP haplotype block partition methods performed better than single SNP method, they were worse than target block.【Conclusion】Due to the short length, the linkage disequilibrium between most of the target sites in liquid-phase 50K SNPs and their mSNPs in same blocks are strong, resulting in target block strategy obtained higher accuracy in haplotype-based genomic selection than single SNP and other haplotype block partition strategies, which could make use of the technique advantage of GBTS, and further broaden the application of liquid-phase chip.

Key words: pig, liquid chip, genomic selection, haplotype, genotyping by target sequencing

Table 1

Data statistics of growth traits and reproductive traits"

达百公斤日龄
Age at 100 kg weight		 达百公斤背膘厚
Backfat thickness at 100 kg weight		 总产仔数
Total born number
表型数据量Number of phenotype records 1267 1267 2898
测定年份Year 2019-2021 2019-2021 2016-2021
系谱记录数Number of pedigree animals 42198

Fig. 1

Flowchart of haplotype matrix construction"

Table 2

Statistics of haplotype number and haplotype allele from different haplotype block partition methods"

统计量
Statistic		 2 SNPs/
block		 5 SNPs/
block		 400 bp/
block		 靶向block
Targeting block
单倍型等位基因数Number of haplotype alleles 153367 210348 238449 240015
单倍型区块数Number of haplotype blocks 44053 17621 42473 42302
每个单倍型区块的平均SNP数
The average number of SNPS per haplotype block		 2 5 2.07 2.08
每个单倍型区块的平均单倍型等位基因数
The average number of haplotype alleles per haplotype block		 3.48 11.94 5.61 5.67
每个单倍型区块的最大SNP数
The maximum number of SNPS per haplotype block		 2 5 7 7
每个单倍型区块的最小SNP数
The minimum number of SNPs per haplotype block		 2 5 1 1
SNP大于等于2的单倍型区块数
The number of haplotype blocks with more than or equal to two SNPs		 44052 17621 21066 21089

Fig. 2

Averaged LD (r2) of adjacent markers in 50K liquid-phase chip, target resequencing data and different kinds of haplotype blocks"

Table 3

The accuracy and unbiasedness of genomic selection on growth and reproduction traits based on SNP and haplotype in younger validation population"

SNP/单倍型
SNP/Haplotype		 单倍型等位基因数或SNP标记数
The number of haplotype alleles or SNP markers		 AGE BF TNB
准确性
Accuracy		 无偏性
Unbiasedness		 准确性Accuracy 无偏性
Unbiasedness		 准确性Accuracy 无偏性Unbiasedness
液相50K SNP
Liquid phase 50K SNP		 42302 0.562 1.139 0.607 1.020 0.596 0.744
靶向重测序mSNP
Target sequencing mSNP		 88105 0.554 1.172 0.599 1.011 0.578 0.745
2 SNPs/block 153367 0.563 1.150 0.608 1.039 0.612 0.736
5 SNPs/block 210348 0.557 1.153 0.604 1.107 0.606 0.743
400 bp/block 238449 0.589 1.134 0.619 1.010 0.632 0.745
靶向block
Target block		 240015 0.589 1.134 0.619 1.010 0.633 0.745

Table 4

The accuracy and unbiasedness of genomic selection on growth and reproduction traits based on SNP and haplotype in five-fold cross validation"

SNP/单倍型
SNP/Haplotype		 AGE BF TNB
准确性
Accuracy		 无偏性
Unbiasedness		 准确性
Accuracy		 无偏性
Unbiasedness		 准确性
Accuracy		 无偏性
Unbiasedness
液相50K SNP
Liquid phase 50K SNP		 0.785±0.004 0.735±0.09 0.736±0.008 0.688±0.11 0.740±0.010 0.929±0.12
靶向重测序mSNP
Target sequencing mSNP		 0.780±0.003 0.756±0.09 0.730±0.007 0.704±0.12 0.725±0.012 0.903±0.11
2 SNPs/block 0.792±0.003 0.744±0.08 0.746±0.007 0.700±0.12 0.751±0.012 0.895±0.11
5 SNPs/block 0.787±0.004 0.747±0.09 0.740±0.007 0.710±0.12 0.746±0.011 0.884±0.11
400 bp/block 0.796±0.003 0.739±0.09 0.748±0.007 0.992±0.48 0.756±0.012 0.897±0.11
靶向 block
Target block		 0.796±0.003 0.739±0.09 0.748±0.007 0.992±0.48 0.756±0.012 0.897±0.11
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