caa a22 4500 397575718 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199603 xx s 000 0 eng 10.1093/hmg/5.3.373 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.3.373 A Unique Origin and Multistep Process for the Generation of Expanded DRPLA Triplet Repeats [Elektronische Daten] [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 T. Potter, S. Robert Young, Koichiro Nakamura, Nobuyuki Nukina, Yoshiro Nagao, Keiko Tadokoro, Torayuki Okuyama, Toshiyuki Miyashita, Tadashi Inoue, Ichiro Kanazawa, Masao Yamada] 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. © 1996 Oxford University Press Yanagisawa Hiroko National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Fujii Katsura National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Nagafuchi Shigeo National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Nakahori Yutaka Departments of Human Genetics, Tokyo 113, Japan aut Nakagome Yasuo Departments of Human Genetics, Tokyo 113, Japan aut Akane Atsushi Department of Legal Medicine, Kansai Medical University, Moriguchi 570, Japan aut Nakamura Masataka Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo 113, Japan aut Sano Akira Department of Neuropsychiatry and Hygiene, Ehime University School of Medicine, Ehime 791-02, Japan aut Komure Osamu Department of Neurology and Psychiatry, Kobe University School of Medicine, Kobe 650, Japan aut Kondo Ikuko Department of Hygiene, Ehime University School of Medicine, Ehime 791-02, Japan aut Kyu Jin Dong Department of Pediatrics, Samsung Medical Center, Seoul 135-230, Korea aut Sørensen Sven A. Department of Medical Genetics, IMBG The Panum Institute, Copenhagen N, Denmark aut Potter Nicholas T. Clinical Molecular Genetics Laboratory, The University of Tennessee Medical Center at Knoxville, Knoxville, TN 37920-6999, USA aut Robert Young S. Department of Obstetrics and Gynecology, South Carolina University, Columbia, SC 29203, USA aut Nakamura Koichiro National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Nukina Nobuyuki Neurology, University of Tokyo, Tokyo 113, Japan aut Nagao Yoshiro National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Tadokoro Keiko National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Okuyama Torayuki National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Miyashita Toshiyuki National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Inoue Tadashi Laboratory of Nucleic Acid Science, Nihon University, Fujisawa 252, Japan aut Kanazawa Ichiro Neurology, University of Tokyo, Tokyo 113, Japan aut Yamada Masao National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut Human Molecular Genetics Oxford University Press 5/3(1996-03), 373-379 0964-6906 5:3<373 1996 5 hmg https://doi.org/10.1093/hmg/5.3.373 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.3.373 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yanagisawa Hiroko National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Fujii Katsura National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Nagafuchi Shigeo National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Nakahori Yutaka Departments of Human Genetics, Tokyo 113, Japan aut NATIONALLICENCE 700 1- Nakagome Yasuo Departments of Human Genetics, Tokyo 113, Japan aut NATIONALLICENCE 700 1- Akane Atsushi Department of Legal Medicine, Kansai Medical University, Moriguchi 570, Japan aut NATIONALLICENCE 700 1- Nakamura Masataka Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo 113, Japan aut NATIONALLICENCE 700 1- Sano Akira Department of Neuropsychiatry and Hygiene, Ehime University School of Medicine, Ehime 791-02, Japan aut NATIONALLICENCE 700 1- Komure Osamu Department of Neurology and Psychiatry, Kobe University School of Medicine, Kobe 650, Japan aut NATIONALLICENCE 700 1- Kondo Ikuko Department of Hygiene, Ehime University School of Medicine, Ehime 791-02, Japan aut NATIONALLICENCE 700 1- Kyu Jin Dong Department of Pediatrics, Samsung Medical Center, Seoul 135-230, Korea aut NATIONALLICENCE 700 1- Sørensen Sven A. Department of Medical Genetics, IMBG The Panum Institute, Copenhagen N, Denmark aut NATIONALLICENCE 700 1- Potter Nicholas T. Clinical Molecular Genetics Laboratory, The University of Tennessee Medical Center at Knoxville, Knoxville, TN 37920-6999, USA aut NATIONALLICENCE 700 1- Robert Young S. Department of Obstetrics and Gynecology, South Carolina University, Columbia, SC 29203, USA aut NATIONALLICENCE 700 1- Nakamura Koichiro National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Nukina Nobuyuki Neurology, University of Tokyo, Tokyo 113, Japan aut NATIONALLICENCE 700 1- Nagao Yoshiro National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Tadokoro Keiko National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Okuyama Torayuki National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Miyashita Toshiyuki National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 700 1- Inoue Tadashi Laboratory of Nucleic Acid Science, Nihon University, Fujisawa 252, Japan aut NATIONALLICENCE 700 1- Kanazawa Ichiro Neurology, University of Tokyo, Tokyo 113, Japan aut NATIONALLICENCE 700 1- Yamada Masao National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/3(1996-03), 373-379 0964-6906 5:3<373 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford