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Genetics, selection, evolution : GSE2014; 46(1); 9; doi: 10.1186/1297-9686-46-9

The utility of low-density genotyping for imputation in the Thoroughbred horse.

Abstract: Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. Results: Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. Conclusions: Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming necessary since researchers are starting to use the recently developed equine 70K SNP chip. However, more work is needed to evaluate the impact of between-breed differences on imputation accuracy.
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Publication Date: 2014-02-04 PubMed ID: 24495673PubMed Central: PMC3930001DOI: 10.1186/1297-9686-46-9Google Scholar: Lookup
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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.

This research focused on how low-density genotyping followed by imputation can provide a cost-effective tool in genomic studies of horses, specifically Thoroughbreds. The study discovers that using a 2K Single Nucleotide Polymorphisms (SNP) panel could offer a good balance between cost and accuracy.

Objective and Methodology of the Study

  • The researchers aimed to explore the prospects of using low-density genotyping and subsequent imputation as a cost-effective approach to amass the large datasets required in the genomic study of diseases in horses.
  • They relied on the haplotype phasing and imputation program, BEAGLE, to examine the feasibility of imputing genotypes from low to high density in the Thoroughbred horse.

Key Findings

  • The study showed that it is possible to impute genotypes from low to high-density with reasonable to high accuracy.
  • The accuracy of the imputation was dependent on both the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and the underlying linkage disequilibrium structure.
  • Equally spacing out SNPs on the low-density panel worked fine, however, ramping up the minor allele frequency of the chosen SNPs provided better results. This advantage remained even when the panel was used in a population from a different geographical origin.
  • Replacing base pair position with linkage disequilibrium map distance reduced the variance in imputation accuracy across SNPs.

Implications and Recommendations

  • The utilization of a 1K SNP panel was usually sufficient to ensure that over 80% of genotypes were accurately imputed. However, other studies suggest that a 2K to 3K panel would minimize subsequent loss of accuracy in genomic prediction analyses.
  • The relationship between accuracy and genotyping costs for different low-density panels indicated that a 2K SNP panel would be a worthwhile investment.
  • Low-density genotyping with a 2K SNP panel followed by imputation could strike a balance between cost and accuracy, promoting widespread genotyping and thus the use of genomic information in horses.
  • This methodology also offers a practical alternate to high-density genotyping while providing a means to combine datasets from different genotyping platforms.
  • The study suggests a need for further research to evaluate the impact of between-breed differences on imputation accuracy.

Cite This Article

APA
Corbin LJ, Kranis A, Blott SC, Swinburne JE, Vaudin M, Bishop SC, Woolliams JA. (2014). The utility of low-density genotyping for imputation in the Thoroughbred horse. Genet Sel Evol, 46(1), 9. https://doi.org/10.1186/1297-9686-46-9

Publication

Genetics, selection, evolution : GSE
ISSN: 1297-9686
NlmUniqueID: 9114088
Country: France
Language: English
Volume: 46
Issue: 1
Pages: 9

Researcher Affiliations

Corbin, Laura J
    Kranis, Andreas
      Blott, Sarah C
        Swinburne, June E
          Vaudin, Mark
            Bishop, Stephen C
              Woolliams, John A
              • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. john.woolliams@roslin.ed.ac.uk.

              MeSH Terms

              • Animals
              • Female
              • Gene Frequency
              • Genome
              • Genotype
              • Genotyping Techniques / economics
              • Genotyping Techniques / methods
              • Horses / genetics
              • Linkage Disequilibrium
              • Male
              • Polymorphism, Single Nucleotide
              • Quantitative Trait, Heritable

              Grant Funding

              • BBS/E/D/20211550 / Biotechnology and Biological Sciences Research Council
              • BBS/E/D/20211554 / Biotechnology and Biological Sciences Research Council

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