A unique origin and multistep process for the generation of expanded DRPLA triplet repeats

Hiroko Yanagisawa, Katsura Fujii, Shigeo Nagafuchi, Yutaka Nakahori, Yasuo Nakagome, Atsushi Akane, Masataka Nakamura, Akira Sano, Osamu Komure, Ikuko Kondo, Dong Kyu Jin, Sven A. Sørensen, Nicholas Potter, S. Robert Young, Koichiro Nakamura, Nobuyuki Nukina, Yoshiro Nagao, Keiko Tadokoro, Torayuki Okuyama, Toshiyuki Miyashita & 3 others Tadashi Inoue, Ichiro Kanazawa, Masao Yamada

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
JournalHuman molecular genetics
Volume5
Issue number3
DOIs
StatePublished - Mar 1 1996

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Progressive Myoclonic Epilepsy
Trinucleotide Repeats
Haplotypes
Ethnic Groups
Human Migration
Human Genome
Neurodegenerative Diseases
Microsatellite Repeats
Epidemiologic Studies
Japan
Chromosomes
Polymerase Chain Reaction
Population

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Yanagisawa, H., Fujii, K., Nagafuchi, S., Nakahori, Y., Nakagome, Y., Akane, A., ... Yamada, M. (1996). A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. Human molecular genetics, 5(3), 373-379. https://doi.org/10.1093/hmg/5.3.373

A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. / Yanagisawa, Hiroko; Fujii, Katsura; Nagafuchi, Shigeo; Nakahori, Yutaka; Nakagome, Yasuo; Akane, Atsushi; Nakamura, Masataka; Sano, Akira; Komure, Osamu; Kondo, Ikuko; Jin, Dong Kyu; Sørensen, Sven A.; Potter, Nicholas; Young, S. Robert; Nakamura, Koichiro; Nukina, Nobuyuki; Nagao, Yoshiro; Tadokoro, Keiko; Okuyama, Torayuki; Miyashita, Toshiyuki; Inoue, Tadashi; Kanazawa, Ichiro; Yamada, Masao.

In: Human molecular genetics, Vol. 5, No. 3, 01.03.1996, p. 373-379.

Research output: Contribution to journalArticle

Yanagisawa, H, Fujii, K, Nagafuchi, S, Nakahori, Y, Nakagome, Y, Akane, A, Nakamura, M, Sano, A, Komure, O, Kondo, I, Jin, DK, Sørensen, SA, Potter, N, Young, SR, Nakamura, K, Nukina, N, Nagao, Y, Tadokoro, K, Okuyama, T, Miyashita, T, Inoue, T, Kanazawa, I & Yamada, M 1996, 'A unique origin and multistep process for the generation of expanded DRPLA triplet repeats', Human molecular genetics, vol. 5, no. 3, pp. 373-379. https://doi.org/10.1093/hmg/5.3.373
Yanagisawa H, Fujii K, Nagafuchi S, Nakahori Y, Nakagome Y, Akane A et al. A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. Human molecular genetics. 1996 Mar 1;5(3):373-379. https://doi.org/10.1093/hmg/5.3.373
Yanagisawa, Hiroko ; Fujii, Katsura ; Nagafuchi, Shigeo ; Nakahori, Yutaka ; Nakagome, Yasuo ; Akane, Atsushi ; Nakamura, Masataka ; Sano, Akira ; Komure, Osamu ; Kondo, Ikuko ; Jin, Dong Kyu ; Sørensen, Sven A. ; Potter, Nicholas ; Young, S. Robert ; Nakamura, Koichiro ; Nukina, Nobuyuki ; Nagao, Yoshiro ; Tadokoro, Keiko ; Okuyama, Torayuki ; Miyashita, Toshiyuki ; Inoue, Tadashi ; Kanazawa, Ichiro ; Yamada, Masao. / A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. In: Human molecular genetics. 1996 ; Vol. 5, No. 3. pp. 373-379.
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