Cystic fibrosis (CF) is a highly variable but inevitably fatal single gene disorder. Several lines of evidence suggest that genetic background contributes to the variability of CF phenotypes. We propose to develop CF as a model for the identification of modifier genes by capitalizing on the availability of a large motivated population of affected twins and siblings. The study has four aims: 1. To identify heritable CF phenotypes by twin study. Intrapair and interpair variance will be determined for selected CF phenotypes, and interclass correlations (MZ vs DZ) will be performed to identify CF phenotypes with a substantial heritable component. 2. To determine the contribution of genetic and other factors to the variability of CF phenotypes by analysis of affected sibs. Variance component methods will be used to evaluate the CF phenotypes that appear to be heritable based upon other studies or the results of aim 1. 3. To identify biologic phenotypes that correlate with heritable CF phenotypes by clinical study of twins and sibs. Multivariate analysis will be used to find biologic phenotypes associated with CF phenotypes. 4. To identify modifier genes and loci responsible for heritable CF phenotypes by linkage approaches. Identity by descent and transmission disequilibrium methods will be used to test linkage between candidate genes/loci and heritable CF phenotypes. To identify novel loci, genome-wide scans will be performed upon sib pairs selected for extreme concordance or discordance for heritable traits.
| Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J et al. (2016) Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis. J Cyst Fibros 15:794-801 |
| Corvol, Harriet; Blackman, Scott M; Boëlle, Pierre-Yves et al. (2015) Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nat Commun 6:8382 |
| Park, Jeenah; Sharma, Neeraj; Cutting, Garry R (2014) Melanocortin 3 receptor has a 5' exon that directs translation of apically localized protein from the second in-frame ATG. Mol Endocrinol 28:1547-57 |
| Morrow, Christopher B; Raraigh, Karen S; Green, Deanna M et al. (2014) Cat and dog exposure and respiratory morbidities in cystic fibrosis. J Pediatr 165:830-5.e2 |
| Collaco, Joseph M; Morrow, Christopher B; Green, Deanna M et al. (2013) Environmental allergies and respiratory morbidities in cystic fibrosis. Pediatr Pulmonol 48:857-64 |
| Blackman, Scott M; Commander, Clayton W; Watson, Christopher et al. (2013) Genetic modifiers of cystic fibrosis-related diabetes. Diabetes 62:3627-35 |
| Green, Deanna M; Collaco, J Michael; McDougal, Kathryn E et al. (2012) Heritability of respiratory infection with Pseudomonas aeruginosa in cystic fibrosis. J Pediatr 161:290-5.e1 |
| Bradley, Gia M; Blackman, Scott M; Watson, Christopher P et al. (2012) Genetic modifiers of nutritional status in cystic fibrosis. Am J Clin Nutr 96:1299-308 |
| Henderson, Lindsay B; Doshi, Vishal K; Blackman, Scott M et al. (2012) Variation in MSRA modifies risk of neonatal intestinal obstruction in cystic fibrosis. PLoS Genet 8:e1002580 |
| Romi, Hila; Cohen, Idan; Landau, Daniella et al. (2012) Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C. Am J Hum Genet 90:893-9 |
Showing the most recent 10 out of 41 publications
