title: Evidence of a common founder for SCA12 in the Indian population.
abstract: Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for approximately 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.
authors.affiliation: Functional Genomics Unit, Institute of Genomics and Integrative Biology, (formerly CBT), CSIR, Mall Road, Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Bahl
authors.forename: K
authors.initials: K
authors.lastname: Virdi
authors.forename: U
authors.initials: U
authors.lastname: Mittal
authors.forename: M P
authors.initials: MP
authors.lastname: Sachdeva
authors.forename: A K
authors.initials: AK
authors.lastname: Kalla
authors.forename: S E
authors.initials: SE
authors.lastname: Holmes
authors.forename: E
authors.initials: E
authors.lastname: O'Hearn
authors.forename: R L
authors.initials: RL
authors.lastname: Margolis
authors.forename: S
authors.initials: S
authors.lastname: Jain
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: M
authors.initials: M
authors.lastname: Mukerji
mesh_terms: D000483:Alleles; D005091:Exons; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2; D012091:Repetitive Sequences, Nucleic Acid; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; C505936:PPP2R2B protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2