Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene.

Journal Article (Journal Article)

A notable difficulty in annotating genomic sequence is identifying the correct start codon in a gene. An important such case has been found with KRIT1, the cerebral cavernous malformation type 1 (CCM1) gene. Analysis of human and mouse genomic sequence encompassing the region containing KRIT1/Krit1 using exon/gene-prediction and comparative alignment programs revealed putative exons upstream of the previously described first exon. These additional candidate exons show significant matches to mouse and human ESTs that are contiguous with and extend upstream from the previously designated 5' end of the KRIT1 cDNA sequence. RT-PCR and 5'RACE experiments confirm the presence of four additional upstream coding exons that encode an additional 207 amino acids. Importantly, a novel frameshift mutation in one of these newly identified KRIT1 exons has been found in a CCM1 family. These data establish the authentic KRIT1 amino acid sequence and suggest that the additional KRIT1 exons may harbor mutations in other CCM1 families. In addition, these results provide another example of the utility of rigorous computational and comparative sequence analysis for refining gene structure.

Full Text

Duke Authors

Cited Authors

  • Sahoo, T; Goenaga-Diaz, E; Serebriiskii, IG; Thomas, JW; Kotova, E; Cuellar, JG; Peloquin, JM; Golemis, E; Beitinjaneh, F; Green, ED; Johnson, EW; Marchuk, DA

Published Date

  • January 1, 2001

Published In

Volume / Issue

  • 71 / 1

Start / End Page

  • 123 - 126

PubMed ID

  • 11161805

International Standard Serial Number (ISSN)

  • 0888-7543

Digital Object Identifier (DOI)

  • 10.1006/geno.2000.6426


  • eng

Conference Location

  • United States