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Mutation analysis and haplotype correlation for 139 cystic fibrosis patients from the Nebraska Regional Cystic
M D Traystman1, N Schulte, J L Colombo
1Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.
Insights
Cystic fibrosis (CF) mutation frequencies were analyzed in 400 individuals. The delta F508 mutation was most common, found in 70% of CF chromosomes, with other mutations also identified.
Area of Science:
- Medical Genetics
- Human Molecular Genetics
Background:
- Cystic Fibrosis (CF) is a prevalent autosomal recessive disorder.
- Understanding CF mutation and haplotype frequencies is crucial for genetic counseling and diagnostics.
Purpose of the Study:
- To determine the frequency of specific Cystic Fibrosis mutations (delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, W1282X) in a regional CF center population.
- To analyze haplotypes associated with these mutations.
Main Methods:
- Genotyping of 139 CF patients, 206 parents, and 55 siblings.
- Analysis of eight specific CF mutations and four genetic markers for haplotype determination.
Main Results:
- The delta F508 mutation was present in 70% of CF chromosomes.
- G542X (6%), G551D (5%), R553X (4%), and R560T (1%) were other identified mutations.
- The E haplotype was most common with the delta F508 deletion.
Conclusions:
- Delta F508 is the predominant CF mutation in this population.
- Haplotype analysis provides insights into mutation origins and distribution.
Abstract:
Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 individuals seen at The Nebraska Regional Cystic Fibrosis Center that included 139 CF patients, 206 parents, and 55 unaffected siblings to determine the frequency of the delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that included XV-2c, KM-19, pMP6d.9, and G2. Results from this study showed that the delta F508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the delta F508 deletion, 47 (34%) were heterozygous for the delta F508 deletion and an unknown mutation, and 18 (13%) carried two unknown mutations. Four additional mutations were also found in our population and included G542X (6%), G551D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that has previously been reported in several families was also present in our study. The most common haplotype associated with the delta F508 deletion in our CF patients was the E haplotype (CF Consortium B) while other mutations were associated with a variety of haplotypes.