Waisfisz Q, Saar K, Morgan N V, Altay C, Leegwater P A, de Winter J P, Komatsu K, Evans G R, Wegner R D, Reis A, Joenje H, Arwert F, Mathew C G, Pronk J C, Digweed M
Departments of Human Genetics, Free University, Amsterdam, Netherlands.
Am J Hum Genet. 1999 May;64(5):1400-5. doi: 10.1086/302385.
Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disease with bone marrow failure and predisposition to cancer as major features, often accompanied by developmental anomalies. The cells of patients with FA are hypersensitive to DNA cross-linking agents in terms of cell survival and chromosomal breakage. Of the eight complementation groups (FA-A to FA-H) distinguished thus far by cell fusion studies, the genes for three-FANCA, FANCC, and FANCG-have been identified, and the FANCD gene has been localized to chromosome 3p22-26. We report here the use of homozygosity mapping and genetic linkage analysis to map a fifth distinct genetic locus for FA. DNA from three families was assigned to group FA-E by cell fusion and complementation analysis and was then used to localize the FANCE gene to chromosome 6p21-22 in an 18.2-cM region flanked by markers D6S422 and D6S1610. This study shows that data from even a small number of families can be successfully used to map a gene for a genetically heterogeneous disorder.
范可尼贫血（FA）是一种遗传性异质性常染色体隐性疾病，主要特征为骨髓衰竭和易患癌症，常伴有发育异常。FA患者的细胞在细胞存活和染色体断裂方面对DNA交联剂高度敏感。通过细胞融合研究迄今已区分出八个互补组（FA-A至FA-H），其中三个组（FANCA、FANCC和FANCG）的基因已被鉴定，FANCD基因已定位到3号染色体p22-26区域。我们在此报告利用纯合性定位和遗传连锁分析来定位FA的第五个不同遗传位点。通过细胞融合和互补分析，将来自三个家族的DNA归入FA-E组，然后用于将FANCE基因定位到6号染色体p21-22区域，该区域位于标记D6S422和D6S1610两侧18.2厘摩的范围内。这项研究表明，即使是来自少数家族的数据也能成功用于定位遗传性异质性疾病的基因。
