AAPS PharmSci

, Volume 3, Issue 4, pp 57–61 | Cite as

Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene

  • Julie L. Lucas
  • Wolfgang Sadee
  • Joseph A. DeYoung
Article

Abstract

The gene encoding the human muscarinic receptor, type 1 (CHRM1), was genotyped from 245 samples of the Coriell Collection (Coriell Institute for Medical Research, Camden, NJ). Fifteen single nucleotide polymorphisms (SNPs) were discovered, 9 of which are located in the coding region of the receptor. Of these, 8 represent synonymous SNPs, indicating that CHRM1 is highly conserved in humans. Only a single allele was found to contain a nonsynonymous SNP, which encodes an amino acid change of Cys to Arg at position 417. This may have functional consequences because a C417S point mutation in rat M1 was previously shown to affect receptor binding and coupling. Furthermore, 0 of 4 SNPs within CHRM1 previously deduced from sequencing of the human genome were found in this study despite a prediction that a majority of such inferred SNPs are accurate. The consensus sequence of CHRM1 obtained in our study differs from the deposited reference sequence (AC NM_000738) in 2 adjacent nucleotides, leading to a V173M change, suggesting a sequencing error in the reference sequence. The extraordinary sequence conservation of the CHRM1 gene-coding region was unexpected as M1-knockout mice show only minimal functional impairments.

Keywords

pharmacogenetics muscarinic acetylcholine receptor single nucleotide polymorphism G protein coupled receptor CHRM1 

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Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  • Julie L. Lucas
    • 1
    • 2
  • Wolfgang Sadee
    • 1
    • 2
  • Joseph A. DeYoung
    • 3
  1. 1.Department of Biopharmaceutical SciencesUniversity of California San FranciscoSan Francisco
  2. 2.Department of Pharmaceutical ChemistryUniversity of California San FranciscoSan Francisco
  3. 3.Genomics Core Facility, Program in Human Genetics, Department of Biochemistry and BiophysicsUniversity of California San FranciscoSan Francisco

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