title: Evolution of the cystatin B gene: implications for the origin of its variable dodecamer tandem repeat in humans.
abstract: The human cystatin B gene contains a variable number of 12-bp tandem repeats in its promoter region, of which the common alleles contain two or three copies and unusual expansion causes progressive myoclonus epilepsy of the Unverricht-Lundborg type. We undertook a comprehensive analysis of the genomic sequence to address the evolutionary events of this variable repeat. By examination of a contiguous genome sequence spanning 5.0 kb and linkage analysis of detected polymorphic changes, we identified six major intragenic haplotypes in unrelated Japanese subjects. The number of normal repeats was closely correlated with these alleles, indicating that changes in the array should be comparatively rare events during human evolution. To examine the origin of the repeat array further, we also analyzed five primate genomes. Repetitive polymorphism was unlikely in hominoids, and the array originated with the dodecamer itself in the course of primate evolution. The variability conceivably developed after the separation to humans.
authors.affiliation: Department of Forensic Medicine, Yamagata University School of Medicine, Yamagata 990-9585, Japan. mosawa@med.id.yamagata-u.ac.jp
authors.forename: Motoki
authors.initials: M
authors.lastname: Osawa
authors.forename: Mika
authors.initials: M
authors.lastname: Kaneko
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitano
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Naruya
authors.initials: N
authors.lastname: Saitou
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umetsu
mesh_terms: D055313:Cystatin B; D015891:Cystatins / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: C524994:CSTB protein, human; D015891:Cystatins; D055313:Cystatin B