title: Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles.
abstract: The role of short, large or intermediate normal alleles (ANs) of the ataxin-2 gene in generating expanded alleles (EAs) causing spinocerebellar ataxia type 2 (SCA2) is poorly understood. It has been postulated that SCA2 prevalence is related to the frequency of large ANs. SCA2 shows the highest worldwide prevalence in Cuban population, which is therefore a unique source for studying the relationship between the frequency of large and intermediate alleles and the frequency of SCA2 mutation. Through genetic polymorphism analyses in a comprehensive sample (~3000 chromosomes), we show that the frequency of large ANs in the ataxin-2 gene is the highest worldwide, although short ANs are also frequent. This highly polymorphic population displayed also high variability in the CAG sequence, featured by loss of the anchor CAA interruption(s). In addition, large ANs showed germinal and somatic instability. Our study also includes related genotypic, genealogical and haplotypic data and provides substantial evidence with regard to the role of large and intermediate alleles in the generation of pathological EAs.
authors.affiliation: Laboratory of Molecular Neurobiology, Centre for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba. mails: laffita@ataxia.hlg.sld.cu
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Laffita-Mesa
authors.forename: Luis C
authors.initials: LC
authors.lastname: Velázquez-Pérez
authors.forename: Nieves
authors.initials: N
authors.lastname: Santos Falcón
authors.forename: Tania
authors.initials: T
authors.lastname: Cruz-Mariño
authors.forename: Yanetza
authors.initials: Y
authors.lastname: González Zaldívar
authors.forename: Yaimee
authors.initials: Y
authors.lastname: Vázquez Mojena
authors.forename: Dennis
authors.initials: D
authors.lastname: Almaguer-Gotay
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Almaguer Mederos
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodríguez Labrada
mesh_terms: D000328:Adult; D000483:Alleles; D000067528:Ataxins; D002877:Chromosomes, Human / Q000235:genetics; D003462:Cuba / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D042822:Genomic Instability; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D015995:Prevalence; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins