Identification of polymorphisms in genes of the immune system in cynomolgus macaques

Identification of polymorphisms in genes of the immune system in cynomolgus macaques Cynomolgus macaques are a standard species used preclinically for evaluating efficacy and toxicity of therapeutic drug candidates and vaccines. However, findings from preclinical studies conducted in cynomolgus macaques are often highly variable, which may in part be attributed to genetic diversity. In this study, genetic polymorphisms were identified in 49 genes of the immune system using DNA isolated from 40 cynomolgus macaques. Of these, 20 originated from a breeding center in China and 20 were of Mauritian origin. A total of 580 polymorphisms were identified, including 561 SNPs, 9 deletions, and 10 insertions with minor allele frequencies ranging from 0.03 to 0.5. Of these genes, 92 % had a SNP distribution frequency >1 per 1,000 bp, illustrating that genes of the immune system in cynomolgus macaques are highly polymorphic. There were 551 common SNPs between the Chinese and Mauritian populations, demonstrating a surprisingly high level of conservation. In silico tools were employed to predict the functional consequences for 264 nonintronic polymorphisms identified. Five polymorphisms were predicted to alter binding of one or more transcription factors, and four were predicted to interfere with miRNA target sites. Additionally, 107 were identified to be nonsynonymous polymorphisms with one causing a frameshift in protein sequence (20,787C deletion in TGF-β1) and three generating premature stop codons (11,990 C>T in IFN-γR2, 11174 C>T in CR1, and 3477 G>T in CTLA-4). Understanding polymorphisms present in cynomolgus macaque genes and their functional consequences will enhance understanding and interpretation of data from preclinical studies conducted in this species. Mammalian Genome Springer Journals

Identification of polymorphisms in genes of the immune system in cynomolgus macaques

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Copyright © 2012 by Springer Science+Business Media, LLC
Life Sciences; Zoology; Cell Biology; Anatomy
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