title: Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation.
abstract: Catechol-O-methyl transferase (COMT) catalyzes the first step in one of the major pathways in the degradation of catecholamines. The COMT gene on chromosome 22 has been considered a candidate gene for many neuropsychiatric disorders, in part because an exon 4 single nucleotide polymorphism (SNP) in COMT causes an amino acid substitution associated with significantly altered enzyme activity. This functional variant, detected as an NlaIII restriction site polymorphism (RSP), is polymorphic in populations from around the world. A four-site haplotype spanning 28 kb effectively encompasses COMT. This haplotype is comprised of two novel polymorphisms [a tetranucleotide short tandem repeat polymorphism (STRP) in intron 1 and a HindIII RSP at the 5' end of COMT], the NlaIII site, and another previously published site - a BglI RSP at the 3' end of the gene. Overall linkage disequilibrium (LD) for this haplotype is strong and significant in 32 population samples from around the world. Conditional probabilities indicate that, in spite of moderate to strong disequilibrium in most non-African populations, the NlaIII site, although often used for prediction, would not always be a reliable predictor of allelic variation at the other sites. Because other functional variation might exist, especially regulatory variation, these findings indicate that haplotypes would be more effective indicators of possible involvement of COMT in disease etiology.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: Mellissa M C
authors.initials: MM
authors.lastname: DeMille
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kidd
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruggeri
authors.forename: Meg A
authors.initials: MA
authors.lastname: Palmatier
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Adekunle
authors.initials: A
authors.lastname: Odunsi
authors.forename: Friday
authors.initials: F
authors.lastname: Okonofua
authors.forename: Elena
authors.initials: E
authors.lastname: Grigorenko
authors.forename: Leslie O
authors.initials: LO
authors.lastname: Schulz
authors.forename: Batsheva
authors.initials: B
authors.lastname: Bonne-Tamir
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
authors.forename: Josef
authors.initials: J
authors.lastname: Parnas
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pakstis
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Kidd
mesh_terms: D001483:Base Sequence; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D017931:DNA Primers; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D011401:Promoter Regions, Genetic
chemical_list: D017931:DNA Primers; D002394:Catechol O-Methyltransferase