title: Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects.
abstract: The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1-R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I-VI), and eye and hair color. A PCR-based approach was used to amplify the full-length coding sequence of the MC1-R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to-glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote.
authors.affiliation: Vollum Institute for Advanced Biomedical Research, Portland, Oregon 97201, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Koppula
authors.forename: L S
authors.initials: LS
authors.lastname: Robbins
authors.forename: D
authors.initials: D
authors.lastname: Lu
authors.forename: E
authors.initials: E
authors.lastname: Baack
authors.forename: C R
authors.initials: CR
authors.lastname: White
authors.forename: N A
authors.initials: NA
authors.lastname: Swanson
authors.forename: R D
authors.initials: RD
authors.lastname: Cone
mesh_terms: D000595:Amino Acid Sequence; D005127:Eye Color / Q000235:genetics; D006200:Hair Color / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011979:Receptors, Pituitary Hormone / Q000235:genetics*
chemical_list: D011979:Receptors, Pituitary Hormone; C029446:MSH receptor