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Home / Equine Research Bank / BMC Genomics / Screening of whole genome sequences identified high-impact v...
BMC genomics2016; 17; 288; doi: 10.1186/s12864-016-2608-3

Screening of whole genome sequences identified high-impact variants for stallion fertility.

Abstract: Stallion fertility is an economically important trait due to the increase of artificial insemination in horses. The availability of whole genome sequence data facilitates identification of rare high-impact variants contributing to stallion fertility. The aim of our study was to genotype rare high-impact variants retrieved from next-generation sequencing (NGS)-data of 11 horses in order to unravel harmful genetic variants in large samples of stallions. Methods: Gene ontology (GO) terms and search results from public databases were used to obtain a comprehensive list of human und mice genes predicted to participate in the regulation of male reproduction. The corresponding equine orthologous genes were searched in whole genome sequence data of seven stallions and four mares and filtered for high-impact genetic variants using SnpEFF, SIFT and Polyphen 2 software. All genetic variants with the missing homozygous mutant genotype were genotyped on 337 fertile stallions of 19 breeds using KASP genotyping assays or PCR-RFLP. Mixed linear model analysis was employed for an association analysis with de-regressed estimated breeding values of the paternal component of the pregnancy rate per estrus (EBV-PAT). Results: We screened next generation sequenced data of whole genomes from 11 horses for equine genetic variants in 1194 human and mice genes involved in male fertility and linked through common gene ontology (GO) with male reproductive processes. Variants were filtered for high-impact on protein structure and validated through SIFT and Polyphen 2. Only those genetic variants were followed up when the homozygote mutant genotype was missing in the detection sample comprising 11 horses. After this filtering process, 17 single nucleotide polymorphism (SNPs) were left. These SNPs were genotyped in 337 fertile stallions of 19 breeds using KASP genotyping assays or PCR-RFLP. An association analysis in 216 Hanoverian stallions revealed a significant association of the splice-site disruption variant g.37455302G>A in NOTCH1 with the de-regressed estimated breeding values of the paternal component of the pregnancy rate per estrus (EBV-PAT). For 9 high-impact variants within the genes CFTR, OVGP1, FBXO43, TSSK6, PKD1, FOXP1, TCP11, SPATA31E1 and NOTCH1 (g.37453246G>C) absence of the homozygous mutant genotype in the validation sample of all 337 fertile stallions was obvious. Therefore, these variants were considered as potentially deleterious factors for stallion fertility. Conclusions: In conclusion, this study revealed 17 genetic variants with a predicted high damaging effect on protein structure and missing homozygous mutant genotype. The g.37455302G>A NOTCH1 variant was identified as a significant stallion fertility locus in Hanoverian stallions and further 9 candidate fertility loci with missing homozygous mutant genotypes were validated in a panel including 19 horse breeds. To our knowledge this is the first study in horses using next generation sequencing data to uncover strong candidate factors for stallion fertility.
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Publication Date: 2016-04-14 PubMed ID: 27079378PubMed Central: PMC4832559DOI: 10.1186/s12864-016-2608-3Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research is aimed at identifying genetic variants that could impact horse fertility using Whole Genome Sequences. The study has discovered 17 such high-impact variants and validated 9 candidate fertility genes that lack homozygous mutant genotype, one of which was found to significantly affect fertility in Hanoverian stallions.

Study Purpose and Methodology

  • The primary goal of the study was to genotype rare, high-impact genetic variants that affect stallion fertility. These variants were identified using next-generation sequencing data from 11 horses.
  • Gene ontology (GO) terms and search results from public databases were utilised to compile an extensive list of human and mice genes linked with the regulation of male reproduction.
  • The corresponding genes in horses were examined using whole genome sequence data from seven stallions and four mares, and then filtered for high-impact genetic variants with the help of SnpEFF, SIFT, and Polyphen 2 software.
  • Genetic variants that lacked the homozygous mutant genotype were genotyped in a panel of 337 fertile stallions belonging to 19 different breeds. This was done using KASP genotyping assays or PCR-RFLP. These variants were then analysed for associations with estimated breeding values of the paternal component of the pregnancy rate per estrus (EBV-PAT) using a mixed linear model.

Results of the Research

  • A total of 1194 human and mice genes related to male fertility were investigated in the genomes of 11 horses. The variants discovered were subjected to a thorough evaluation and filtered based on their high-impact on protein structure.
  • After the filtering process, 17 single nucleotide polymorphism (SNPs) were identified. These SNPs were then genotyped in 337 stallions of 19 different breeds.
  • A splice-site disruption variant, g.37455302G>A in the NOTCH1 gene, was found to have a significant association with the estimated breeding values of the paternal component of the pregnancy rate per estrus (EBV-PAT) in Hanoverian stallions.
  • Nine high-impact variants within the CFTR, OVGP1, FBXO43, TSSK6, PKD1, FOXP1, TCP11, SPATA31E1, and NOTCH1 (g.37453246G>C) genes were found to have no homozygous mutant genotype in all the 337 fertile stallions, indicating that these variants could potentially harm stallion fertility.

Conclusion of the Study

  • The study identified 17 genetic variants with a high predicted damaging effect on protein structure and a lack of homozygous mutant genotype.
  • Among them, the NOTCH1 variant g.37455302G>A was found to have a significant impact on stallion fertility in Hanoverian stallions.
  • Additionally, nine candidate fertility loci without homozygous mutant genotypes were identified as potentially harmful factors for stallion fertility.
  • This research is groundbreaking as it is the first study in horses that uses next generation sequencing data to uncover influential factors for stallion fertility.

Cite This Article

APA
Schrimpf R, Gottschalk M, Metzger J, Martinsson G, Sieme H, Distl O. (2016). Screening of whole genome sequences identified high-impact variants for stallion fertility. BMC Genomics, 17, 288. https://doi.org/10.1186/s12864-016-2608-3

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 17
Pages: 288

Researcher Affiliations

Schrimpf, Rahel
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünteweg 17p, 30559, Hannover, Germany.
Gottschalk, Maren
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünteweg 17p, 30559, Hannover, Germany.
Metzger, Julia
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünteweg 17p, 30559, Hannover, Germany.
Martinsson, Gunilla
  • State Stud Celle of Lower Saxony, Spörckenstraße 10, 29221, Celle, Germany.
Sieme, Harald
  • Clinic for Horses, Unit for Reproduction Medicine, University of Veterinary Medicine Hannover, Bünteweg 15, 30559, Hannover, Germany.
Distl, Ottmar
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bünteweg 17p, 30559, Hannover, Germany. ottmar.distl@tiho-hannover.de.

MeSH Terms

  • Animals
  • Breeding
  • Computational Biology
  • DNA Mutational Analysis
  • Female
  • Fertility / genetics
  • Genotype
  • Genotyping Techniques
  • High-Throughput Nucleotide Sequencing
  • Homozygote
  • Horses / genetics
  • Infertility, Male / genetics
  • Insemination, Artificial
  • Male
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pregnancy, Animal

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