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BMC genomics2019; 20(1); 174; doi: 10.1186/s12864-019-5564-x

High-resolution population structure and runs of homozygosity reveal the genetic architecture of complex traits in the Lipizzan horse.

Abstract: The sample ascertainment bias due to complex population structures remains a major challenge in genome-wide investigations of complex traits. In this study we derived the high-resolution population structure and levels of autozygosity of 377 Lipizzan horses originating from five different European stud farms utilizing the SNP genotype information of the high density 700 k Affymetrix Axiom™ Equine genotyping array. Scanning the genome for overlapping runs of homozygosity (ROH) shared by more than 50% of horses, we identified homozygous regions (ROH islands) in order to investigate the gene content of those candidate regions by gene ontology and enrichment analyses. Results: The high-resolution population network approach revealed well-defined substructures according to the origin of the horses (Austria, Slovakia, Croatia and Hungary). The highest mean genome coverage of ROH (S) was identified in the Austrian (S = 342.9), followed by Croatian (S = 214.7), Slovakian (S = 205.1) and Hungarian (S = 171.5) subpopulations. ROH island analysis revealed five common islands on ECA11 and ECA14, hereby confirming a closer genetic relationship between the Hungarian and Croatian as well as between the Austrian and Slovakian samples. Private islands were detected for the Hungarian and the Austrian Lipizzan subpopulations. All subpopulations shared a homozygous region on ECA11, nearly identical in position and length containing among other genes the homeobox-B cluster, which was also significantly (p < 0.001) highlighted by enrichment analysis. Gene ontology terms were mostly related to biological processes involved in embryonic morphogenesis and anterior/posterior specification. Around the STX17 gene (causative for greying), we identified a ROH island harbouring the genes NR4A3, STX17, ERP44 and INVS. Within further islands on ECA14, ECA16 and ECA20 we detected the genes SPRY4, NDFIP1, IMPDH2, HSP90AB1, whereas SPRY4 and HSP90AB1 are involved in melanoma metastasis and survival rate of melanoma patients in humans. Conclusions: We demonstrated that the assessment of high-resolution population structures within one single breed supports the downstream genetic analyses (e.g. the identification of ROH islands). By means of ROH island analyses, we identified the genes SPRY4, NDFIP1, IMPDH2, HSP90AB1, which might play an important role for further studies on equine melanoma. Furthermore, our results highlighted the impact of the homeobox-A and B cluster involved in morphogenesis of Lipizzan horses.
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Publication Date: 2019-03-05 PubMed ID: 30836959PubMed Central: PMC6402180DOI: 10.1186/s12864-019-5564-xGoogle 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.

The research studied the genetic structure and traits of the Lipizzan horse, a breed originating from Europe, using a high density genotyping array. The dense array allowed to look for shared clusters of homozygosity, which are regions of the genome where both alleles are the same. These areas were then analyzed to understand their potential functions. The results demonstrated a significant impact of genes involved in embryonic development and a potential role of certain genes in equine melanoma.

High-resolution population structure in the Lipizzan horse

  • The researchers utilized the high density 700k Affymetrix Axiom™ Equine genotyping array, a tool which allowed them to assess the SNP (single-nucleotide polymorphism) genotype information for an extensive sample of 377 Lipizzan horses from several European stud farms.
  • The application of this high-resolution technique allowed the researchers to identify clear population substructures among the horses based on their country of origin including Austria, Slovakia, Croatia, and Hungary.
  • The highest frequency of homozygosity, or Genome-wide runs of homozygosity (ROH), was found in Austrian horses, followed by Croatian, Slovakian, and then Hungarian.

Identification and analysis of homozygous regions

  • The researchers scanned for overlapping runs of homozygosity (ROH) that were present in more than half of the horses studied.
  • From there, they identified ROH islands, these are genomic regions with high levels of homozygosity, these islands, even though separated in the genome could comprise of genes with similar functions or participating in common pathways.
  • Common homozygous regions were identified on two chromosomes (ECA11 and ECA14), suggesting a closer genetic relationship between Lipizzan horses from Hungary and Croatia, and between those from Austria and Slovakia.

Gene ontology and enrichment analyses

  • The identified homozygous regions were subjected to gene ontology and enrichment analyses to gain insights about the likely biological roles of these genes.
  • The regions identified harbor a number of genes known to influence embryonic development and possibly contribute to the specific appearance of the Lipizzan horse breed.
  • A ROH island surrounding the gene STX17, which is linked with the greying of hair, contained a number of other relevant genes, including those involved in pigmentation and melanoma in human studies.
  • The findings suggest that some identified genes, like SPRY4, NDFIP1, IMPDH2, and HSP90AB1, may have significant implications for equine melanoma research, while others might have played a genetic role in the morphogenesis of Lipizzan horses.

Cite This Article

APA
Grilz-Seger G, Druml T, Neuditschko M, Dobretsberger M, Horna M, Brem G. (2019). High-resolution population structure and runs of homozygosity reveal the genetic architecture of complex traits in the Lipizzan horse. BMC Genomics, 20(1), 174. https://doi.org/10.1186/s12864-019-5564-x

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 20
Issue: 1
Pages: 174
PII: 174

Researcher Affiliations

Grilz-Seger, Gertrud
  • Institute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210, Vienna, Austria.
Druml, Thomas
  • Institute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210, Vienna, Austria. thomas.druml@vetmeduni.ac.at.
Neuditschko, Markus
  • Agroscope, Swiss National Stud Farm, Les Longs Prés, CH-1580, Avenches, Switzerland.
Dobretsberger, Max
  • Institute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210, Vienna, Austria.
Horna, Michaela
  • Department of Animal Husbandry, Slovak University of Agriculture in Nitra, Nitra-Chrenová, Slovak Republic.
Brem, Gottfried
  • Institute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210, Vienna, Austria.

MeSH Terms

  • Animals
  • Female
  • Genetics, Population
  • Genome / genetics
  • Genotype
  • Homozygote
  • Horses / genetics
  • Inbreeding
  • Male
  • Multifactorial Inheritance / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics

Grant Funding

  • 843464 / u00d6sterreichische Forschungsfu00f6rderungsgesellschaft
  • 101332 / Bundesministerium fu00fcr Nachhaltigkeit und Tourismus (AT)

Conflict of Interest Statement

ETHICS APPROVAL: This study was discussed and approved by the institutional Commission for Ethics and Animal Welfare, University of Veterinary Medicine, Vienna, protocol number: ETK-06/05/2015, in accordance with GSP guidelines and national legislation. CONSENT FOR PUBLICATION: The Lipizzan state stud farms Piber (Austria), Topol’čianky (Slovakia), Lipik, Đakovo (Croatia) and Szilvasvárad (Hungary) granted the permission to take hair samples from their horses. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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