Dataset Information

A Large-Scale Genome-Wide Association Study in U.S. Holstein Cattle.

ABSTRACT: Genome-wide association study (GWAS) is a powerful approach to identify genomic regions and genetic variants associated with phenotypes. However, only limited mutual confirmation from different studies is available. We conducted a large-scale GWAS using 294,079 first-lactation Holstein cows and identified new additive and dominance effects on five production traits, three fertility traits, and somatic cell score. Four chromosomes had the most significant SNP effects on the five production traits, a Chr14 region containing DGAT1 mostly had positive effects on fat yield and negative effects on milk and protein yields, the 88.07-89.60 Mb region of Chr06 with SLC4A4, GC, NPFFR2, and ADAMTS3 for milk and protein yields, the 30.03-36.67 Mb region of Chr20 with C6 and GHR for milk yield, and the 88.19-88.88 Mb region with ABCC9 as well as the 91.13-94.62 Mb region of Chr05 with PLEKHA5, MGST1, SLC15A5, and EPS8 for fat yield. For fertility traits, the SNP in GC of Chr06, and the SNPs in the 65.02-69.43 Mb region of Chr01 with COX17, ILDR1, and KALRN had the most significant effects for daughter pregnancy rate and cow conception rate, whereas SNPs in AFF1 of Chr06, the 47.54-52.79 Mb region of Chr07, TSPAN4 of Chr29, and NPAS1 of Chr18 had the most significant effects for heifer conception rate. For somatic cell score, GC of Chr06 and PRLR of Chr20 had the most significant effects. A small number of dominance effects were detected for the production traits with far lower statistical significance than the additive effects and for fertility traits with similar statistical significance as the additive effects. Analysis of allelic effects revealed the presence of uni-allelic, asymmetric, and symmetric SNP effects and found the previously reported DGAT1 antagonism was an extreme antagonistic pleiotropy between fat yield and milk and protein yields among all SNPs in this study.

SUBMITTER: Jiang J

PROVIDER: S-EPMC6527781 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Large-Scale Genome-Wide Association Study in U.S. Holstein Cattle.

Jiang Jicai J Ma Li L Prakapenka Dzianis D VanRaden Paul M PM Cole John B JB Da Yang Y

Frontiers in genetics 20190514

Genome-wide association study (GWAS) is a powerful approach to identify genomic regions and genetic variants associated with phenotypes. However, only limited mutual confirmation from different studies is available. We conducted a large-scale GWAS using 294,079 first-lactation Holstein cows and identified new additive and dominance effects on five production traits, three fertility traits, and somatic cell score. Four chromosomes had the most significant SNP effects on the five production traits ...[more]

PMID: 31139206

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Project description:BACKGROUND: Breeding for enhanced immune response (IR) has been suggested as a tool to improve inherent animal health. Dairy cows with superior antibody-mediated (AMIR) and cell-mediated immune responses (CMIR) have been demonstrated to have a lower occurrence of many diseases including mastitis. Adaptive immune response traits are heritable, and it is, therefore, possible to breed for improved IR, decreasing the occurrence of disease. The objective of this study was to perform genome-wide association studies to determine differences in genetic profiles among Holstein cows classified as High or Low for AMIR and CMIR. From a total of 680 cows with immune response phenotypes, 163 cows for AMIR (81 High and 82 Low) and 140 for CMIR (75 High and 65 Low) were selectively genotyped using the Illumina Bovine SNP50 BeadChip. Results were validated using an unrelated population of 164 Holstein bulls IR phenotyped for AMIR and 146 for CMIR. RESULTS: A generalized quasi likelihood score method was used to determine single nucleotide polymorphisms (SNP) and chromosomal regions associated with immune response. After applying a 5% chromosomal false discovery rate, 186 SNPs were significantly associated with AMIR. The majority (93%) of significant markers were on chromosome 23, with a similar peak found in the bull population. For CMIR, 21 SNP markers remained significant. Candidate genes within 250,000 base pairs of significant SNPs were identified to determine biological pathways associated with AMIR and CMIR. Various pathways were identified, including the antigen processing and presentation pathway, important in host defense. Candidate genes included those within the bovine Major Histocompatability Complex such as BoLA-DQ, BoLA-DR and the non-classical BoLA-NC1 for AMIR and BoLA-DQ for CMIR, the complement system including C2 and C4 for AMIR and C1q for CMIR, and cytokines including IL-17A, IL17F for AMIR and IL-17RA for CMIR and tumor necrosis factor for both AMIR and CMIR. Additional genes associated with CMIR included galectins 1, 2 and 3, BCL2 and ?-defensin. CONCLUSIONS: The significant genetic variation associated with AMIR and CMIR in this study may imply feasibility to include immune response in genomic breeding indices as an approach to improve inherent animal health.

Project description:Simple Summary Udder conformation traits are economically important for dairy animals in the dairy industry. Milk production loss can be reduced via a better udder structure in dairy cattle. Udder traits are related to milk production and the somatic cell count, which is a sign of mammary infections (mastitis); as such, it is vital to understand the genetic architecture underlying udder traits in Holstein Friesian cattle for genetic development and long-term selection. Through a GWAS on udder structure traits in Chinese Holstein cattle, we identified several significant single-nucleotide polymorphisms (SNPs) and candidate genes associated with udder traits. The results could provide useful information regarding the genetics architecture of udder structure traits, thus improving the genetic information, health, longevity, and production of dairy cattle. Abstract Udder conformation traits are one of the most economic traits in dairy cows, greatly affecting animal health, milk production, and producer profitability in the dairy industry. Genetic analysis of udder structure and scores have been developed in Holstein cattle. In our research, we conducted a genome-wide association study for five udder traits, including anterior udder attachment (AUA), central suspensory ligament (CSL), posterior udder attachment height (PUAH), posterior udder attachment width (PUAW), and udder depth (UD), in which the fixed and random model circulating probability unification (FarmCPU) model was applied for the association analysis. The heritability and the standard errors of these five udder traits ranged from 0.04 ± 0.00 to 0.49 ± 0.03. Phenotype data were measured from 1000 Holstein cows, and the GeneSeek Genomic Profiler (GGP) Bovine 100 K SNP chip was used to analyze genotypic data in Holstein cattle. For GWAS analysis, 984 individual cows and 84,407 single-nucleotide polymorphisms (SNPs) remained after quality control; a total of 18 SNPs were found at the GW significant threshold (p < 5.90 × 10−7). Many candidate genes were identified within 200kb upstream or downstream of the significant SNPs, which include MGST1, MGST2, MTUS1, PRKN, STXBP6, GRID2, E2F8, CDH11, FOXP1, SLF1, TMEM117, SBF2, GC, ADGRB3, and GCLC. Pathway analysis revealed that 58 Gene Ontology (GO) terms and 18 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched with adjusted p values, and these GO terms and the KEGG pathway analysis were associated with biological information, metabolism, hormonal growth, and development processes. These results could give valuable biological information for the genetic architecture of udder conformation traits in dairy Holstein cattle.

Project description:BackgroundSingle nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations.ResultsModerate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but < 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained).ConclusionsFourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species.

Dataset Information

A Large-Scale Genome-Wide Association Study in U.S. Holstein Cattle.

Publications

A Large-Scale Genome-Wide Association Study in U.S. Holstein Cattle.

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