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PloS one2013; 8(2); e55434; doi: 10.1371/journal.pone.0055434

Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

Abstract: Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.
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Publication Date: 2013-02-08 PubMed ID: 23408978PubMed Central: PMC3568152DOI: 10.1371/journal.pone.0055434Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
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  • 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 article focuses on the comparative study of the Angiotensin converting enzyme (ACE) gene in horses of various breeds, identifying a highly conserved potential transcription factor binding site. It aims to understand its possible contribution to the regulation of inter-individual variation in enzyme levels and its link to various health conditions and physical abilities.

Background

  • The ACE gene plays a crucial role in blood pressure control.
  • In humans, a polymorphism (variation) exists in the ACE gene, specifically an Alu insertion/deletion (I/D) in one of its introns (non-coding regions), which has been tied to variations in serum enzyme levels.
  • This human ACE gene polymorphism has been linked with a variety of health conditions including cardiovascular disease, type II diabetes, renal disease, and even elite athleticism, however, the functional mechanism of this is still unclear.

ACE Gene Characterization in Horses

  • In this study, the researchers characterized the ACE gene in horses, specifically those of breeds selected for varying physical capabilities.
  • The structure of the equine ACE gene was found to be similar to all known mammalian ACE genes.
  • Nine common single nucleotide polymorphisms (SNPs) were found in the equine ACE gene, which were inherited in nine different ways (haplotypes).
  • Three of these SNPs were located in intron 16, in a location homologous (the same) as that containing the Alu polymorphism in humans.

Discovery of a Conserved Sequence

  • A particularly conserved 18 base pair sequence was discovered within intron 16, and it is proposed to be a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β.
  • This putative regulatory element may play a role in the inter-individual differences in ACE enzyme levels.
  • Two of the SNPs discovered in horses occur within this conserved area, but neither disrupt the potential transcription binding site.

Conclusion and Implications

  • The authors suggest a new potential regulatory mechanism for the ACE gene in mammalian species, which could explain the observed inter-individual variations in enzyme levels, and its link to various health conditions and physical abilities.
  • This discovery opens up opportunities for further research to better comprehend the mechanisms behind the associations seen between the human Alu polymorphism and enzyme levels, disease states, and athleticism.

Cite This Article

APA
Hamilton NA, Tammen I, Raadsma HW. (2013). Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16. PLoS One, 8(2), e55434. https://doi.org/10.1371/journal.pone.0055434

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 2
Pages: e55434
PII: e55434

Researcher Affiliations

Hamilton, Natasha A
  • ReproGen-Animal Bioscience Group, Faculty of Veterinary Science, University of Sydney, Camperdown, New South Wales, Australia. natasha.hamilton@sydney.edu.au
Tammen, Imke
    Raadsma, Herman W

      MeSH Terms

      • Animals
      • Base Sequence
      • Binding Sites
      • DNA, Complementary / genetics
      • Horses
      • Humans
      • Introns
      • Likelihood Functions
      • Molecular Sequence Data
      • Peptidyl-Dipeptidase A / genetics
      • Polymorphism, Single Nucleotide
      • Reverse Transcriptase Polymerase Chain Reaction
      • Sequence Homology, Nucleic Acid
      • Transcription Factors / metabolism

      Conflict of Interest Statement

      The authors of this paper also hold the inventors rights within the related patent “Equine performance test” International Patent Application no pct/au2007/001379. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

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      Citations

      This article has been cited 2 times.
      1. Yang S, Oksenberg N, Takayama S, Heo SJ, Poliakov A, Ahituv N, Dubchak I, Boffelli D. Functionally conserved enhancers with divergent sequences in distant vertebrates. BMC Genomics 2015 Oct 30;16:882.
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      2. Dubchak I, Balasubramanian S, Wang S, Cem M, Sulakhe D, Poliakov A, Börnigen D, Xie B, Taylor A, Ma J, Paciorkowski AR, Mirzaa GM, Dave P, Agam G, Xu J, Al-Gazali L, Mason CE, Ross ME, Maltsev N, Gilliam TC. An integrative computational approach for prioritization of genomic variants. PLoS One 2014;9(12):e114903.
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