Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populations

Lucia F. Jorge-Nebert, Zhengwen Jiang, Ranajit Chakraborty, Joanna Watson, Li Jin, Stephen T. McGarvey, Ranjan Deka, Daniel W. Nebert

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The human CYP1A1-CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head-to-head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60 CYP1A1-CYP1A2 SNPs found in the present study (eight New Guinea Highlanders, eight Samoans, four Dogrib, four Teribe, four Pehuenche, and one Caucasian) with those found in a previous study (six West Africans, four Han Chinese, six Germans, four Samoans, and four Dogrib), yielding a total of 106 SNPs in 106 chromosomes. Resequencing of Oceanians plus Amerindians in the present study yielded 21 New World SNPs (∼20%), of which 17 are not previously reported in any SNP database. Various tests revealed selective pressures for both genes and both haploblocks; unfortunately, differences in rates of evolution between the two genes were undetectable. Fay & Wu's H test revealed a "hitchhiking event" centered around four SNPs in the CYP1A1 3′-UTR; a study in silico identified different microRNA-binding patterns in the hitchhiked region, when the mutations were present compared with the mutations absent.

Original languageEnglish
Pages (from-to)27-40
Number of pages14
JournalHuman Mutation
Volume31
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • AHR
  • Aryl hydrocarbon receptor
  • CYP1A1
  • CYP1A2
  • microRNA

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