title: A unique origin and multistep process for the generation of expanded DRPLA triplet repeats.
abstract: Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder associated with the expansion of a CAG repeat at chromosome band 12p13. Epidemiological studies have demonstrated an increased prevalence of DRPLA in Japan, although several DRPLA kindreds of non-Japanese ancestry have been identified. To define the molecular basis for this geographic variation in prevalence, we have analyzed haplotypes around the repeat in several different ethnic groups. Two intragenic biallelic polymorphisms distinguished three haplotypes, each of which formed a predominant haplotype found in the three major racial populations. All the expanded repeats of Japanese and Caucasian patients studied were associated with a particular haplotype, which otherwise was associated with longer repeats commonly found in Asians. Our results support a multi-step model for repeat expansion, and suggest that expanded DRPLA repeats may have evolved from an ancient chromosomal haplotype of Asian origin. We also propose that a combination of a highly polymorphic microsatellite marker with relatively stable biallelic markers in a range of PCR amplification is a powerful tool for studies on human genome diversity, which may reveal the ancient human migration and the formation of ethnic groups.
authors.affiliation: National Children's Medical Research Center, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yanagisawa
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakahori
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagome
authors.forename: A
authors.initials: A
authors.lastname: Akane
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Sano
authors.forename: O
authors.initials: O
authors.lastname: Komure
authors.forename: I
authors.initials: I
authors.lastname: Kondo
authors.forename: D K
authors.initials: DK
authors.lastname: Jin
authors.forename: S A
authors.initials: SA
authors.lastname: Sørensen
authors.forename: N T
authors.initials: NT
authors.lastname: Potter
authors.forename: S R
authors.initials: SR
authors.lastname: Young
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Nukina
authors.forename: Y
authors.initials: Y
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: T
authors.initials: T
authors.lastname: Okuyama
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D001741:Black or African American; D000818:Animals; D044466:Asian People; D044383:Black People; D002648:Child; D005060:Europe; D005787:Gene Frequency; D005819:Genetic Markers; D005917:Globus Pallidus / Q000473:pathology*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D009422:Nervous System Diseases / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012012:Red Nucleus / Q000473:pathology*; D012091:Repetitive Sequences, Nucleic Acid; D018911:Trinucleotide Repeats; D044465:White People
chemical_list: D005819:Genetic Markers