Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1

An 800-kb region on chromosome 8q21, which complements the phenotype of cel ls from Nijmegen breakage syndrome patients, is a candidate for the locus o f the underlying gene, termed NBS1. The sequence of this 800-kb region of D NA indicated that the size of this segment is 755,832 bp with an additional 36-kb gap. From this region, we identified four genes including NBS1, a ge ne coding for a 27-kDa vitamin D-dependent calcium-binding protein (27-kDa calbindin), the mitochondrial 2,4-dienoyl-CoA reductase gene, and a novel g ene, C8orf1/hT41. All four genes were aligned in a 250-kb centromeric porti on of the region, and no gene was found in the remaining telomeric portion containing 500 kb. The genomic organization of the C8orf1/hT41 and NBS1 gen es has been analyzed using the computer programs GRAIL 2 and GENSCAN. They predicted and successfully found more than 93% of the exons, even a small 5 4-bp exon, indicating that one or more exons in any gene can be identified by these programs. GENSCAN was more efficient at locating the four genes th an GRAIL 2 and identified 15 of the 16 exons of the NBS1 gene. This 800-kb region contained repetitive sequences, including 179 copies of the Alu sequ ence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107 co pies of the LTR sequence (1 copy/7.1 kb), and 63 copies of the MER sequence (1 copy/12 kb). There was a slight but not significant difference in the r epetitive content of the gene-rich region and the remaining noncoding regio n. Our results indicate that computer-assisted methods are useful and power ful for identifying exons of both known and novel genes. (C) 1999 Academic Press.