Park Joonhong, Kim Myungshin, Jang Woori, Chae Hyojin, Kim Yonggoo, Chung Nack-Gyun, Lee Jae-Wook, Cho Bin, Jeong Dae-Chul, Park In Yang, Park Mi Sun
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Ann Hum Genet. 2015 May;79(3):153-61. doi: 10.1111/ahg.12097. Epub 2015 Feb 20.
A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population.
在患有范可尼贫血（FA）的韩国和日本患者中，强烈提示存在一个共同的祖先单倍型，因为经常发现常见突变：FANCA基因的c.2546delC和c.3720_3724delAAACA；FANCG基因的c.307+1G>C、c.1066C>T和c.1589_1591delATA。本研究的目的是调查FANCA和FANCG这些常见突变的起源。我们对13名FA患者进行了基因分型，其中包括5名来自韩国FA人群的FA-A患者和8名FA-G患者。用于单倍型分析的微卫星标记包括与FANCA紧密连锁的4个CA重复标记和与FANCG相邻的8个CA重复标记。结果，携带c.2546delC或c.3720_3724delAAACA的韩国FA-A患者没有共享相同的单倍型。然而，三种携带c.307+1G>C、c.1066C>T或c.1589_1591delATA的独特单倍型，由覆盖侧翼区域的8个多态性位点组成，与韩国FA-G患者密切相关，这与先前在日本FA-G人群中报道的奠基者单倍型一致。我们的发现证实了东亚FA-G患者起源上的共同祖先单倍型，这将增进我们对FA-G分子群体遗传学的理解。据我们所知，这是关于韩国FA人群中疾病相关突变与共同祖先单倍型之间关联的首次报道。
