Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene
- Hospital for Sick Children, Toronto, Ontario (Canada)
- Tel Aviv Univ. (Israel)
- Chaim Sheba Medical Center, Tel Hashomer (Israel)
- Univ. of Toronto, Ontario (Canada)
- Univ. of Michigan, Ann Arbor (United States)
- Hospital for Sick Children, Toronto, Ontario (Canada) Univ. of Toronto, Ontario (Canada)
Additional mutations in the cystic fibrosis (CF) gene were identified in the regions corresponding to the two putative nucleotide (ATP)-binding folds (NBFs) of the predicted polypeptide. The patient cohort included 46 Canadian CF families with well-characterized DNA marker haplotypes spanning the disease locus and several other families from Israel. Eleven mutations were found in the first NBF, 2 were found in the second NBF, but none was found in the R-domain. Seven of the mutations were of the missense type affecting some of the highly conserved amino acid residues in the first NBF; 3 were nonsense mutations; 2 would probably affect mRNA splicing; 2 corresponded to small deletions, including another 3-base-pair deletion different from the major mutation ({delta}F508), which could account for 70% of the CF chromosomes in the population. Nine of these mutations accounted for 12 of the 31 non-{delta}F508 CF chromosomes in the Canadian families. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward.
- OSTI ID:
- 5702360
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:21; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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FIBROSIS
BIOLOGICAL MARKERS
GENE MUTATIONS
DNA SEQUENCING
HEREDITARY DISEASES
PATHOGENESIS
DNA POLYMERASES
PATIENTS
POLYPEPTIDES
RECOMBINANT DNA
DISEASES
DNA
ENZYMES
MUTATIONS
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PEPTIDES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
550201* - Biochemistry- Tracer Techniques