Identifying pleiotropic variants and candidate genes for fertility and reproduction traits in Holstein cattle via association studies based on imputed whole-genome sequence genotypes

Chen, Shiyi; Schenkel, F. S.; Melo, Ana Lúcia Puerro de; Oliveira, Hinayah Rojas de; Pedrosa, Victor Breno; Araujo, André Campêlo; Melka, Melkaye G.; Brito, Luiz F.

doi:10.1186/s12864-022-08555-z

Cited by 24 publications

(17 citation statements)

References 153 publications

(186 reference statements)

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“…In the 26.92–32.60 Mb of Chr23, the most significant SNPs were in three genes with unknown functions, LOC537017 , LOC101905956 , and C23H6orf10 ( Table 1 ). This relatively large chromosome region (6.32 Mb in size) had multiple genes with or near highly significant SNP effects (log 10 (1/ p ) > 20), but only the non-classical MHC class I gene of BOLA-NC1 was reported to affect reproduction [ 10 , 11 , 12 , 13 ].The significant SNP closest to BOLA-NC1 was rs110855962 with log 10 (1/ p ) = 21.02 ( Figure 1 d).…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows

Prakapenka

Liang

2023

IJMS

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A genome-wide association study (GWAS) of age at first calving (AFC) using 813,114 first lactation Holstein cows and 75,524 SNPs identified 2063 additive effects and 29 dominance effects with p-values < 10−8. Three chromosomes had highly significant additive effects in the regions of 7.86–8.12 Mb of Chr15, 27.07–27.48 Mb and 31.25–32.11 Mb of Chr19, and 26.92–32.60 Mb of Chr23. Two of the genes in those regions were reproductive hormone genes with known biological functions that should be relevant to AFC, the sex hormone binding globulin (SHBG) gene, and the progesterone receptor (PGR) gene. The most significant dominance effects were near or in EIF4B and AAAS of Chr05 and AFF1 and KLHL8 of Chr06. All dominance effects were positive overdominance effects where the heterozygous genotype had an advantage, and the homozygous recessive genotype of each SNP had a very negative dominance value. Results from this study provided new evidence and understanding about the genetic variants and genome regions affecting AFC in U.S. Holstein cows.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows

Prakapenka

Liang

2023

IJMS

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“…Neither SNP is located in a region previously associated with female reproductive traits [70]. These SNPs have also not been previously reported to be associated with fertility traits in previous investigations that focused on sire-centric models [4,[33][34][35][36][37], nor on studies that focused on genotyped heifers only [32,38].…”

Section: Discussionmentioning

confidence: 81%

“…Another potential avenue for the identification of infertile heifers is the use of molecular phenotyping [24]. The pioneering efforts focused on genome-wide association studies (GWAS) to identify genetic markers associated with heifer fertility [4,12,[25][26][27][28][29][30][31][32][33][34][35][36][37][38], but only a few seem to be reproducible across populations [37]. More recent efforts have also focused on transcriptome [39][40][41] and metabolome [42] datasets characterizing these molecules in blood samples.…”

Section: Introductionmentioning

confidence: 99%

A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Marrella

Biase

2022

Preprint

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Background: Infertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production. Results: Using a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7x10-7; and rs109366560, chr11:37666527, P = 2.6x10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm = 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm = 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category. Conclusions: Our multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.

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“…The region identified on BTA25, with the increasing allele coming from the B. taurus ancestor, is contained within a QTL region previously reported for persistency of milk yield in Holstein cattle ( Harder et al, 2006 ), and overlaps with a region for milking speed in French Holstein cattle ( Marete et al, 2018 ) and North American Holstein cattle ( Chen et al, 2020 ). Previous GWAS had also reported this region to be associated with fertility and reproduction traits in Holstein cattle (e.g., Jaton et al, 2018 ; Chen et al, 2022 ).…”

Section: Discussionmentioning

confidence: 86%

Detection of genomic regions that differentiate Bos indicus from Bos taurus ancestral breeds for milk yield in Indian crossbred cows

Kalaldeh

Swaminathan²,

Podtar³

et al. 2023

Front. Genet.

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Introduction: In India, crossbred cows incorporate the high production of B. taurus dairy breeds and the environmental adaptation of local B. indicus cattle. Adaptation to different environments and selection in milk production have shaped the genetic differences between B. indicus and B. taurus cattle. The aim of this paper was to detect, for milk yield of crossbred cows, quantitative trait loci (QTL) that differentiate B. indicus from B. taurus ancestry, as well as QTL that are segregating within the ancestral breeds.Methods: A total of 123,042 test-day milk records for 4,968 crossbred cows, genotyped with real and imputed 770 K SNP, were used. Breed origins were assigned to haplotypes of crossbred cows, and from that, were assigned to SNP alleles.Results: At a false discovery rate (FDR) of 30%, a large number of genomic regions showed significant effects of B. indicus versus B. taurus origin on milk yield, with positive effects coming from both ancestors. No significant regions were detected for Holstein Friesian (HF) versus Jersey effects on milk yield. Additionally, no regions for SNP alleles segregating within indigenous, within HF, and within Jersey were detected. The most significant effects, at FDR 5%, were found in a region on BTA5 (43.98–49.44 Mbp) that differentiates B. indicus from B. taurus, with an estimated difference between homozygotes of approximately 10% of average yield, in favour of B. indicus origin.Discussion: Our results indicate that evolutionary differences between B. indicus and B. taurus cattle for milk yield, as expressed in crossbred cows, occur at many causative loci across the genome. Although subject to the usual first estimation bias, some of the loci appear to have large effects that might make them useful for genomic selection in crossbreds, if confirmed in subsequent studies.

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Identifying pleiotropic variants and candidate genes for fertility and reproduction traits in Holstein cattle via association studies based on imputed whole-genome sequence genotypes

Cited by 24 publications

References 153 publications

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows

A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Detection of genomic regions that differentiate Bos indicus from Bos taurus ancestral breeds for milk yield in Indian crossbred cows

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