Complete nanopore repeat sequencing of SCA27B (GAA-FGF14 ataxia) in Japanese.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miyatake Satoko, Doi Hiroshi, Yaguchi Hiroaki, Koshimizu Eriko, Kihara Naoki, Matsubara Tomoyasu, Mori Yasuko, Kunieda Kenjiro, Shimizu Yusaku, Toyota Tomoko, Shirai Shinichi, Matsushima Masaaki, Okubo Masaki, Wada Taishi, Kunii Misako, Johkura Ken, Miyamoto Ryosuke, Osaki Yusuke, Miyama Takabumi, Satoh Mai, Fujita Atsushi, Uchiyama Yuri, Tsuchida Naomi, Misawa Kazuharu, Hamanaka Kohei, Hamanoue Haruka, Mizuguchi Takeshi, Morino Hiroyuki, Izumi Yuishin, Shimohata Takayoshi, Yoshida Kunihiro, Adachi Hiroaki, Tanaka Fumiaki, Yabe Ichiro, Matsumoto Naomichi
Аннотация
METHODS: We screened FGF14 repeat expansion in a Japanese cohort of 460 molecularly undiagnosed adult-onset cerebellar ataxia patients and 1022 controls, together with 92 non-Japanese controls, and performed nanopore sequencing of FGF14 repeat expansion.
RESULTS: In the Japanese population, the GCA motif was predominantly observed as the non-GAA motif, whereas the GGA motif was frequently detected in non-Japanese controls. The 5'-common flanking variant was observed in all Japanese GAA repeat alleles within normal length, demonstrating its meiotic stability against repeat expansion. In both patients and controls, pure GAA repeat was up to 400 units in length, whereas non-pathogenic GAA-GCA repeat was larger, up to 900 units, but they evolved from different haplotypes, as rs534066520, located just upstream of the repeat sequence, completely discriminated them. Both (GAA)≥250 and (GAA)≥200 were enriched in patients, whereas (GAA-GCA)≥200 was similarly observed in patients and controls, suggesting the pathogenic threshold of (GAA)≥200 for cerebellar ataxia. We identified 14 patients with SCA27B (3.0%), but their single-nucleotide polymorphism genotype indicated different founder alleles between Japanese and Caucasians. The low prevalence of SCA27B in Japanese may be due to the lower allele frequency of (GAA)≥250 in the Japanese population than in Caucasians (0.15% vs 0.32%-1.26%).
CONCLUSIONS: FGF14 repeat expansion has unique features of pathogenicity and allelic origin, as revealed by a single ethnic study.