A genome‐wide association study suggests new candidate genes for milk production traits in Chinese Holstein cattle

Yue, Shujian; Zhao, Yiqiang; Gu, X. R.; Yin, Bin; Jiang, Yunliang; Wang, Z. H.; Shi, Kerong

doi:10.1111/age.12593

Cited by 28 publications

(21 citation statements)

References 18 publications

(16 reference statements)

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“…For example, GWAS with contiguous genome assemblies identified candidate loci associated with tuberculosis susceptibility and recombination hot spots in wild boar and Soay sheep, respectively (Johnston, Bérénos, Slate, & Pemberton, ; Queirós, Alves, Vicente, Gortázar, & de la Fuente, ). GWAS and genomic selection are now routine approaches to improve selective breeding in agriculture and horticulture, for example to investigate beef and milk production traits in cattle (Sorbolini et al, ; Yue et al, ) and growth and fatness in pigs (Guo et al, ).…”

Section: Introductionmentioning

confidence: 99%

Improving Illumina assemblies with Hi‐C and long reads: An example with the North African dromedary

Elbers

Rogers

Perelman

et al. 2019

Molecular Ecology Resources

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Researchers have assembled thousands of eukaryotic genomes using Illumina reads, but traditional mate‐pair libraries cannot span all repetitive elements, resulting in highly fragmented assemblies. However, both chromosome conformation capture techniques, such as Hi‐C and Dovetail Genomics Chicago libraries and long‐read sequencing, such as Pacific Biosciences and Oxford Nanopore, help span and resolve repetitive regions and therefore improve genome assemblies. One important livestock species of arid regions that does not have a high‐quality contiguous reference genome is the dromedary ( Camelus dromedarius ). Draft genomes exist but are highly fragmented, and a high‐quality reference genome is needed to understand adaptation to desert environments and artificial selection during domestication. Dromedaries are among the last livestock species to have been domesticated, and together with wild and domestic Bactrian camels, they are the only representatives of the Camelini tribe, which highlights their evolutionary significance. Here we describe our efforts to improve the North African dromedary genome. We used Chicago and Hi‐C sequencing libraries from Dovetail Genomics to resolve the order of previously assembled contigs, producing almost chromosome‐level scaffolds. Remaining gaps were filled with Pacific Biosciences long reads, and then scaffolds were comparatively mapped to chromosomes. Long reads added 99.32 Mbp to the total length of the new assembly. Dovetail Chicago and Hi‐C libraries increased the longest scaffold over 12‐fold, from 9.71 Mbp to 124.99 Mbp and the scaffold N50 over 50‐fold, from 1.48 Mbp to 75.02 Mbp. We demonstrate that Illumina de novo assemblies can be substantially upgraded by combining chromosome conformation capture and long‐read sequencing.

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Section: Introductionmentioning

confidence: 99%

Improving Illumina assemblies with Hi‐C and long reads: An example with the North African dromedary

Elbers

Rogers

Perelman

et al. 2019

Molecular Ecology Resources

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“…Genome-wide association study (GWAS) is a commonly used strategy to identify potential genetic variants underlying important complex traits in human and domestic animals. So far, some candidate genes and QTL regions for milk production traits have been detected with GWA studies in dairy cattle, such as DLGAP1, AP2B1, SCD, BTA11 (1.59 ~ 3.37 Mbp), and BTA3 (70.34 ~ 73.69 Mbp) [11][12][13][14][15][16]. In our previous GWAS for milk FAs in Chinese Holstein cows, 83 genome-wide signi cant single nucleotide polymorphisms (SNPs) were detected in total [15], in which, two SNPs (ARS-BFGL-NGS-109493 and BTA-56389-no-rs) associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3phosphate O-acyltransferase 3 (AGPAT3) gene.…”

Section: Introductionmentioning

confidence: 99%

A Post-GWAS Confirming the Genetic Effects and Functional Polymorphisms of AGPAT3 Gene on Milk Fatty Acids in Dairy Cattle

Shi

Zhu²,

Lv³

et al. 2020

Preprint

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Background: In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3,000bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1,065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with medium-chain saturated fatty acids (C6:0, C8:0 and C10:0; P < 0.0001~ 0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G>A, g.146704373A>G g.146704618A>G and g.146704699G>A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A>G and g.146704618A>G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk medium-chain saturated FAs in dairy cattle, and two potential causal mutations were detected.

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“…SNPs from the X chromosome were counted due to the overall majority of female individuals in the study population. After the data quality control procedure (Yue et al, 2017;Yan et al, 2019), 361 animals with 41,092 SNP genotypes were finally retained for the subsequent GWAS analysis. Physical map length, the number of SNPs, and the SNP density on each chromosome, before and after the data cleaning procedure, are shown in Supplementary Table S2.…”

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confidence: 99%

“…The similarity might reflect the sharing of breeding histories among the cattle. Multidimensional scaling (MDS) analysis of 12,380 independent SNP markers (Purcell et al, 2007;Yue et al, 2017;Yan et al, 2019) with r 2 < 0.2 (Wang et al, 2009), using the first and the second components, indicating that there was slight population stratification (Supplementary Figure S2). To better correct cryptic population stratification, the first MDS component was used to be the covariate in the following genome-wide association analysis (Supplementary Figure S3).…”

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confidence: 99%

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Identification of Whole-Genome Significant Single Nucleotide Polymorphisms in Candidate Genes Associated With Serum Biochemical Traits in Chinese Holstein Cattle

et al. 2020

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A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E−06 and 2.43E−06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E−06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene LOC101903458 on chromosome 8) was identified to be significantly associated with serum high-and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.

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A genome‐wide association study suggests new candidate genes for milk production traits in Chinese Holstein cattle

Cited by 28 publications

References 18 publications

Improving Illumina assemblies with Hi‐C and long reads: An example with the North African dromedary

Improving Illumina assemblies with Hi‐C and long reads: An example with the North African dromedary

A Post-GWAS Confirming the Genetic Effects and Functional Polymorphisms of AGPAT3 Gene on Milk Fatty Acids in Dairy Cattle

Identification of Whole-Genome Significant Single Nucleotide Polymorphisms in Candidate Genes Associated With Serum Biochemical Traits in Chinese Holstein Cattle

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