Localization of the fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3

Fanconi anemia (FA) is a rare autosomal recessive disease manifested by bon e-marrow failure and an elevated incidence of cancer. Cells taken from pati ents exhibit spontaneous chromosomal breaks and rearrangements. These break s and rearrangements are greatly elevated by treatment of FA cells with the use of DNA cross-linking agents. The FA complementation group D gene (FANC D) has previously been localized to chromosome 3p22-26, by use of microcell -mediated chromosome transfer. Here we describe the use of noncomplemented microcell hybrids to identify small overlapping deletions that narrow the F ANCD critical region. A 1.2-Mb bacterial-artificial-chromosome (BAC)/P1 con tig was constructed, bounded by the marker D3S3631 distally and by the gene ATP2B2 proximally. The contig contains at least 36 genes, including the ox ytocin receptor (OXTR), hOGG1, the von Hippel-Lindau tumor-suppressor gene (VHL), and IRAK-2. Both hOGG1 and IRAK-2 were excluded as candidates for FA NCD. BACs were then used as probes for FISH analyses, to map the extent of the deletions in four of the noncomplemented microcell hybrid cell lines. A narrow region of common overlapping deletions limits the FANCD critical re gion to similar to 200 kb. The three candidate genes in this region are TIG R-A004X28, SGC34603, and AA609512.