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

Genomics. 1999 Jan 15;55(2):242-7. doi: 10.1006/geno.1998.5657.

Abstract

An 800-kb region on chromosome 8q21, which complements the phenotype of cells from Nijmegen breakage syndrome patients, is a candidate for the locus of the underlying gene, termed NBS1. The sequence of this 800-kb region of DNA 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 gene 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 gene, C8orf1/hT41. All four genes were aligned in a 250-kb centromeric portion 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 genes 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 54-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 than 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 sequence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107 copies 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 repetitive content of the gene-rich region and the remaining noncoding region. Our results indicate that computer-assisted methods are useful and powerful for identifying exons of both known and novel genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Calbindins
  • Chromosome Breakage*
  • Chromosomes, Bacterial
  • Chromosomes, Human, Pair 8*
  • Exons / genetics
  • Fatty Acid Desaturases / genetics
  • Humans
  • Introns / genetics
  • Male
  • Molecular Sequence Data
  • Oxidoreductases Acting on CH-CH Group Donors*
  • S100 Calcium Binding Protein G / genetics
  • Sequence Analysis, DNA
  • Software
  • Syndrome
  • Testis / metabolism

Substances

  • Calbindins
  • S100 Calcium Binding Protein G
  • Fatty Acid Desaturases
  • Oxidoreductases Acting on CH-CH Group Donors
  • 2,4-dienoyl-CoA reductase

Associated data

  • GENBANK/AB015752
  • GENBANK/AF061326