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Home / Equine Research Bank / Anim Genet / Evidence That GYPA (Glycophorin A) Encodes the K Blood Group...
Animal genetics2026; 57(2); e70083; doi: 10.1002/age.70083

Evidence That GYPA (Glycophorin A) Encodes the K Blood Group System in Horses.

Abstract: Although serological and genetic studies of equine blood group systems have been conducted for many years, the molecular basis of erythrocyte antigens' variability has remained largely unexplored. In this study, we aimed to elucidate the genetic basis of serological variation within equine blood group K. Using mRNA extracted from peripheral blood samples (n = 100) collected from horses with known serological blood types (Ka or K-), we performed a transcriptome-wide association study (TWAS), which revealed a significantly associated region on equine chromosome 2 (ECA2). A detailed analysis of this region identified GYPA (glycophorin A) as the most promising candidate gene. Resequencing its entire coding sequence revealed the presence of a dinucleotide missense variant in exon 3 (ENSECAT00000026370.3:c.145_146delinsAT; p.Asp49Ile), which is predicted to potentially alter the function of the GYPA protein. Genotyping this variant in a large, breed-diverse cohort, which included family-based samples, confirmed perfect cosegregation between the identified GYPA missense substitution and serological K blood group typing results. Our findings demonstrate that blood transcriptome-based approaches, despite certain limitations, can effectively reveal the molecular basis of equine erythrocyte antigen variability.
© 2026 Stichting International Foundation for Animal Genetics.
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Publication Date: 2026-03-16 PubMed ID: 41837461DOI: 10.1002/age.70083Google 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.

Overview

  • This study identifies the gene GYPA as responsible for the K blood group system in horses by linking a specific genetic variant to blood type differences seen in horse blood samples.

Background

  • Previous research has characterized equine blood group systems through serological (blood serum) and genetic studies, but the precise molecular causes of blood group antigen differences in horses had not been fully identified.
  • Blood groups in horses are important for transfusions and breeding but the genetic variations that cause the different blood group antigen profiles were unclear, especially for the K blood group.

Research Goal

  • The primary aim was to discover the genetic basis underlying the serological variation observed in the equine K blood group system.
  • Understanding this could improve blood typing accuracy and inform veterinary medicine practices regarding blood transfusions and compatibility.

Methods

  • Peripheral blood samples were collected from 100 horses, all previously typed for the K blood group antigen as either positive (Ka) or negative (K-).
  • Extracted messenger RNA (mRNA) from these blood samples was used to perform a transcriptome-wide association study (TWAS), which analyzes gene expression patterns to find genetic regions linked to the blood types.
  • A statistically significant association between the K blood group phenotype and a region on chromosome 2 (ECA2) was found.
  • Within this region, the GYPA gene, which encodes glycophorin A, a known erythrocyte (red blood cell) membrane protein involved in human blood group systems, emerged as the top candidate gene.
  • The full coding sequence of GYPA was resequenced to identify genetic variants; a dinucleotide missense mutation (a precise substitution of two nucleotides leading to an amino acid change) was discovered in exon 3 of GYPA.
  • This mutation changes amino acid 49 from aspartic acid (Asp) to isoleucine (Ile), which is predicted to affect protein function.
  • The presence of this genetic variant was assessed in a large, genetically diverse horse population, including related individuals (family-based samples), to verify its inheritance pattern and association with the K blood group status.

Key Findings

  • The identified GYPA missense mutation perfectly co-segregated with serologically determined K blood group types in all tested horses, showing a strong genetic correlation.
  • This co-segregation means that horses carrying the mutation expressed the K antigen whereas those lacking it did not, confirming GYPA as the genetic basis for the K blood group.
  • This discovery links a specific genetic variant in the GYPA gene to the phenotypic variation in equine blood groups, which had not been molecularly confirmed before in horses.

Implications and Conclusions

  • The study demonstrates that transcriptome-based genomic approaches can successfully uncover molecular determinants of erythrocyte antigen variability in equine species despite challenges such as sample diversity and gene expression complexity.
  • Identification of the genetic cause of the K blood group can improve accuracy in blood typing and transfusion compatibility testing in horses, which are critical for veterinary care and breeding management.
  • Understanding the molecular basis can also serve as a foundation for developing genetic tests to predict K blood group status without relying solely on serological assays.
  • This research paves the way for further molecular investigations of other equine blood group systems to enhance veterinary hematology and immunogenetics.

Cite This Article

APA
Mackowski M, Kajdasz A, Laskowska K, Cieslak J. (2026). Evidence That GYPA (Glycophorin A) Encodes the K Blood Group System in Horses. Anim Genet, 57(2), e70083. https://doi.org/10.1002/age.70083

Publication

Animal genetics
ISSN: 1365-2052
NlmUniqueID: 8605704
Country: England
Language: English
Volume: 57
Issue: 2
Pages: e70083

Researcher Affiliations

Mackowski, Mariusz
  • Department of Genetics and Animal Breeding, Poznań University of Life Sciences, Poznań, Poland.
Kajdasz, Arkadiusz
  • Laboratory of Bioinformatics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
Laskowska, Kaja
  • Department of Genetics and Animal Breeding, Poznań University of Life Sciences, Poznań, Poland.
Cieslak, Jakub
  • Department of Genetics and Animal Breeding, Poznań University of Life Sciences, Poznań, Poland.

MeSH Terms

  • Animals
  • Horses / genetics
  • Horses / blood
  • Glycophorins / genetics
  • Blood Group Antigens / genetics

Grant Funding

  • 2022/47/B/NZ9/02331 / Narodowe Centrum Nauki

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