Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study.
The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.
Department of Laboratory Medicine, North Carolina Memorial Hospital, Chapel Hill.
W E
WE
Highsmith
G L
GL
Chong
H T
HT
Orr
T R
TR
Perry
D
D
Schald
R
R
Farber
K
K
Wagner
M R
MR
Knowles
W J
WJ
Warwick
L M
LM
Silverman
D001483:Base Sequence; D002872:Chromosome Deletion; D003550:Cystic Fibrosis / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015341:Nucleic Acid Probes; D010641:Phenotype; D010649:Phenylalanine / Q000172:deficiency / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012306:Risk
D015341:Nucleic Acid Probes; D010649:Phenylalanine