Cystic fibrosis in the United Arab Emirates: II-molecular genetic analysis

ABSTRACT

In order to identify the genetic mutations responsible for cystic fibrosis among United Arab Emirate nationals, we designed a pilot project that allowed the screening of 17 out of the 27 exons of the cystic fibrosis transmembrane conductance regulator gene [this gene encodes a 1480 amino acid long protein]. In order to detect rapidly any sequence change in the corresponding gene regions, we chose a strategy that was based on the techniques of denaturing gradient gel electrophoresis combined with asymmetric amplification DNA sequencing. A common mutation called the delta F 508 deletion, which accounts for 70% of cystic fibrosis chromosomes screened worldwide, was absent from the eight affected families. We discovered, however, that a T to G mutation resulting in the replacement of a serine by an arginine at position 549 of the protein [S549R] accounts for 75% of cystic fibrosis chromosomes studied [12 out of the 16 chromosomes that were screened in this study]. We also identified several polymorphisms that will be useful in the study of the co-segregation of deleterious alleles in most or all families affected by cystic fibrosis in the country