title: Identification of four novel polymorphisms in the calcitonin/alpha-CGRP (CALCA) gene and an investigation of their possible associations with Parkinson disease, schizophrenia, and manic depression.
abstract: We identified novel polymorphisms in the calcitonin/CGRPalpha (CALCA) gene by direct sequencing of genomic DNA and subsequent genotyping by RFLP (restriction fragment length polymorphism) detection and investigated association with neurological or psychiatric disease. Four novel polymorphic alleles were found: two (g.979G>A and g.4218T>C) represented single nucleotide polymorphisms (SNPs), one consisted of two coupled SNPs in close vicinity to each other (g.1210T>C and g.1214C>G), and one was an intronic 16-bp microdeletion (2919-2934del16). One of the SNPs (g.4218T>C) causes a non-synonymous amino acid change (Leu66Pro) in the third exon, an exon common to both procalcitonin and pro-alpha-CGRP. In a subsequent association study, frequencies of the identified polymorphisms in Parkinson and schizophrenia patients were compared with frequencies in the normal population. No statistically significant association was found in our material. The 16-bp microdeletion polymorphism was present in a family with multiple cases of unipolar or bipolar depressive disorder. Using this polymorphism as marker, cosegregation with the phenotype was observed in the majority of individuals.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Berzelius väg 3, 17177 Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Buervenich
authors.forename: F
authors.initials: F
authors.lastname: Xiang
authors.forename: O
authors.initials: O
authors.lastname: Sydow
authors.forename: E G
authors.initials: EG
authors.lastname: Jönsson
authors.forename: G C
authors.initials: GC
authors.lastname: Sedvall
authors.forename: M
authors.initials: M
authors.lastname: Anvret
authors.forename: L
authors.initials: L
authors.lastname: Olson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D002116:Calcitonin / Q000737:chemistry / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000235:genetics*; D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013548:Sweden; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D004298:Dopamine