title: Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene.
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.
authors.affiliation: Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, CA 94143-0446, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Lucas
authors.forename: J A
authors.initials: JA
authors.lastname: DeYoung
authors.forename: W
authors.initials: W
authors.lastname: Sadee
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D004247:DNA / Q000235:genetics; D006801:Humans; D008715:Methionine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D004247:DNA; D008715:Methionine; D014633:Valine