Gene mapping, gene-set analysis, and genomic prediction of postpartum blood calcium in Holstein cows

Cavani, Lígia; Poindexter, M.B.; Nelson, Corwin D.; Santos, J.E.P.; Peñagaricano, Francisco

doi:10.3168/jds.2021-20872

Cited by 10 publications

(11 citation statements)

References 48 publications

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“…By comparing eQTLs and eGenes in early-mid lactation with cGTEx, some eQTLs and eGenes with specific effects during early to mid lactation were found. GO terms enriched by these specific eGenes are interesting, for example, glucose can affect milk protein synthesis [ 28 ], and calcium is essential for milk synthesis [ 29 ]. However, it should be noted that the number of SNPs, sample size, composition of breeds, and other information used in this study and in cGTEx for eQTL identification differ.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Tang,

Zhang,

et al. 2024

BMC Genomics

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Background Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22–150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. Results We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. Conclusions This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Tang,

Zhang,

et al. 2024

BMC Genomics

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“…For all six traits studied, there are many common candidate genes detected in TD35 and TD50, such as seven genes among 20 candidate genes for FP, which may be due to the relatively close lactation interval of TD35 and TD50, and the high genetic correlation (greater than 0.9); thus, the mechanisms affecting the traits are similar. NDST4 is associated with milk fever in the U.S. Holstein cattle ( Cavani et al, 2022 ). In a previous study of milk production traits in Canadian Holstein at different lactation stages, SCRIB on BTA14 was a candidate gene for MY and was associated with TD95 to TD215 of PY ( Oliveira et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic parameters and genome-wide association for milk production traits and somatic cell score in different lactation stages of Shanghai Holstein population

Liu

Zhao

et al. 2022

Front. Genet.

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The aim of this study was to investigate the genetic parameters and genetic architectures of six milk production traits in the Shanghai Holstein population. The data used to estimate the genetic parameters consisted of 1,968,589 test-day records for 305,031 primiparous cows. Among the cows with phenotypes, 3,016 cows were genotyped with Illumina Bovine SNP50K BeadChip, GeneSeek Bovine 50K BeadChip, GeneSeek Bovine LD BeadChip v4, GeneSeek Bovine 150K BeadChip, or low-depth whole-genome sequencing. A genome-wide association study was performed to identify quantitative trait loci and genes associated with milk production traits in the Shanghai Holstein population using genotypes imputed to whole-genome sequences and both fixed and random model circulating probability unification and a mixed linear model with rMVP software. Estimated heritabilities (h2) varied from 0.04 to 0.14 for somatic cell score (SCS), 0.07 to 0.22 for fat percentage (FP), 0.09 to 0.27 for milk yield (MY), 0.06 to 0.23 for fat yield (FY), 0.09 to 0.26 for protein yield (PY), and 0.07 to 0.35 for protein percentage (PP), respectively. Within lactation, genetic correlations for SCS, FP, MY, FY, PY, and PP at different stages of lactation estimated in random regression model were ranged from -0.02 to 0.99, 0.18 to 0.99, 0.04 to 0.99, 0.04 to 0.99, 0.01 to 0.99, and 0.33 to 0.99, respectively. The genetic correlations were highest between adjacent DIM but decreased as DIM got further apart. Candidate genes included those related to production traits (DGAT1, MGST1, PTK2, and SCRIB), disease-related (LY6K, COL22A1, TECPR2, and PLCB1), heat stress–related (ITGA9, NDST4, TECPR2, and HSF1), and reproduction-related (7SK and DOCK2) genes. This study has shown that there are differences in the genetic mechanisms of milk production traits at different stages of lactation. Therefore, it is necessary to conduct research on milk production traits at different stages of lactation as different traits. Our results can also provide a theoretical basis for subsequent molecular breeding, especially for the novel genetic loci.

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“…With regard to the LRRC38 segment, the SNP effect correlations between DD and the production traits MY, FY, and PY were significant and positive. LRRC38 is actively involved in K transport and is associated with postpartum Ca concentration in blood and in milk of Holstein cows (Cavani et al, 2022). Calcium in turn plays an important role in milk production (Breves et al, 2016), as well as in keratinization and mature horn cell formation of the claw (Langova et al, 2020).…”

Section: Genetic Correlations and Snp Effect Correlations Among Claw ...mentioning

confidence: 99%

Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress

Sölzer

May

Yin

et al. 2022

Journal of Dairy Science

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The aim of the present study was an in-depth genomic analysis to understand the genomic mechanisms of the 3 claw disorders dermatitis digitalis (DD), interdigital hyperplasia (HYP), and sole ulcer (SU). In this regard, we estimated genetic parameters based on genomic relationship matrices, performed genome-wide association studies, annotated potential candidate genes, and inferred genetic associations with breeding goal traits considering the most important chromosomal segments. As a further novelty of this study, we inferred possible SNP × heat stress interactions for claw disorders. The study consisted of 17,264 first-lactation Holstein Friesian cows kept in 50 large-scale contract herds. The disease prevalence was 15.96, 2.36, and 8.20% for DD, HYP, and SU, respectively. The remaining breeding goal traits consisted of type traits of the feet and leg composite, female fertility, health traits, and 305-d production traits. The final genotype data set included 44,474 SNPs from the 17,264 genotyped cows. Heritabilities for DD, HYP, and SU were estimated in linear and threshold models considering the genomic relationship matrix (G matrix). Genetic correlations with breeding goal traits based on G were estimated in a series of bivariate linear models, which were verified via SNP effect correlations for specific chromosome segments (i.e., segments harboring potential candidate genes for DD, HYP, and SU). Genome-wide association studies were performed for all traits in a case-control design by applying a single SNP linear mixed model. Furthermore, for DD, HYP, and SU, we modeled SNP × heat stress interactions in genome-wide association studies. Single nucleotide polymorphism-based heritabilities were 0.04 and 0.08 for DD, 0.03 and 0.10 for SU, and 0.03 and 0.23 for HYP from linear and threshold models, respectively. The genetic correlations between DD, HYP, and SU with conformation traits from the feet and leg composite were positive throughout, indicating the value of indirect selection on conformation traits to improve claw health. Genetic correlations between DD, SU, and HYP with other breeding goal traits indicated impaired female fertility, impaired udder health status, and productivity decline of diseased cows. Genetic correlations among DD, SU, and HYP were moderate to large, indicating that different claw disorders have similar genetic mechanisms. Nevertheless, we identified disease-specific potential candidate genes, and genetic associations based on the surrounding SNPs partly differed from the genetic correlations. Especially for candidate genes contributing to 2 traits simultaneously, correlations based on SNP effects from the respective chromosome segment were close to 1 or to −1. In this regard, we annotated the candidate genes KRT33A and KRT33B for HYP and DD, KIF27 for HYP and calving to first insemination, and MAN1A1 for SU and the production traits. For SNP × heat stress interactions, we identified significant SNPs on BTA 2, 4, 5, 7, 8, 9, 13, 22, 25, and 28, and we annotated the potential candidate...

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Gene mapping, gene-set analysis, and genomic prediction of postpartum blood calcium in Holstein cows

Cited by 10 publications

References 48 publications

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Genetic parameters and genome-wide association for milk production traits and somatic cell score in different lactation stages of Shanghai Holstein population

Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress

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