Comparative human-horse sequence analysis of the CYP3A subfamily gene cluster

Schmitz, Andrea; Demmel, Steffi; Peters, Laureen Michèle; Leeb, Tosso; Mevissen, Meike; Haase, Bianca (2010). Comparative human-horse sequence analysis of the CYP3A subfamily gene cluster. Animal genetics, 41(s2), pp. 72-79. Oxford: Blackwell 10.1111/j.1365-2052.2010.02111.x

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Cytochrome P450 enzymes (CYP450s) represent a superfamily of haem-thiolate proteins. CYP450s are most abundant in the liver, a major site of drug metabolism, and play key roles in the metabolism of a variety of substrates, including drugs and environmental contaminants. Interaction of two or more different drugs with the same enzyme can account for adverse effects and failure of therapy. Human CYP3A4 metabolizes about 50% of all known drugs, but little is known about the orthologous CYP450s in horses. We report here the genomic organization of the equine CYP3A gene cluster as well as a comparative analysis with the human CYP3A gene cluster. The equine CYP450 genes of the 3A family are located on ECA 13 between 6.97-7.53 Mb, in a region syntenic to HSA 7 99.05-99.35 Mb. Seven potential, closely linked equine CYP3A genes were found, in contrast to only four genes in the human genome. RNA was isolated from an equine liver sample, and the approximately 1.5-kb coding sequence of six CYP3A genes could be amplified by RT-PCR. Sequencing of the RT-PCR products revealed numerous hitherto unknown single nucleotide polymorphisms (SNPs) in these six CYP3A genes, and one 6-bp deletion compared to the reference sequence (EquCab2.0). The presence of the variants was confirmed in a sample of genomic DNA from the same horse. In conclusion, orthologous genes for the CYP3A family exist in horses, but their number differs from those of the human CYP3A gene family. CYP450 genes of the same family show high homology within and between mammalian species, but can be highly polymorphic.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
UniBE Contributor:	Schmitz, Andrea, Demmel, Steffi, Peters, Laureen Michèle, Leeb, Tosso, Mevissen, Meike, Haase, Bianca
Subjects:	600 Technology > 630 Agriculture 500 Science > 590 Animals (Zoology)
ISSN:	0268-9146
Publisher:	Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:33
Last Modified:	17 Sep 2023 00:21
Publisher DOI:	10.1111/j.1365-2052.2010.02111.x
Web of Science ID:	000284117700012
URI:	https://boris.unibe.ch/id/eprint/12796 (FactScience: 219268)