Relating the disease mutation spectrum to the evolution of the cystic fibrosis transmembrane conductance regulator (CFTR).

ABSTRACT: Cystic fibrosis (CF) is the most common genetic disease among Caucasians, and accordingly the cystic fibrosis transmembrane conductance regulator (CFTR) protein has perhaps the best characterized disease mutation spectrum with more than 1,500 causative mutations having been identified. In this study, we took advantage of that wealth of mutational information in an effort to relate site-specific evolutionary parameters with the propensity and severity of CFTR disease-causing mutations. To do this, we devised a scoring scheme for known CFTR disease-causing mutations based on the Grantham amino acid chemical difference matrix. CFTR site-specific evolutionary constraint values were then computed for seven different evolutionary metrics across a range of increasing evolutionary depths. The CFTR

SUBMITTER: Rishishwar L 

PROVIDER: S-EPMC3413703 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature