Abstract

Cystic fibrosis is a fatal disease caused by defects in CFTR, a chloride channel that is essential for ion and fluid transport in epithelial tissues. Variability in CF disease course and complications, even in patients with identical CFTR genotypes, indicates that other genetic, environmental, or stochastic (random) factors also contribute. Twin studies have revealed that genetic factors other than CFTR underlie much of the risk for two significant complications of CF: meconium ileus, a severe neonatal intestinal obstruction, and CF-related diabetes, which is correlated with increased CF complications and reduced survival. A genome-wide scan has led to identification of genetic loci likely to be linked to these phenotypes. In this project a candidate gene approach will be used to identify genes within these linkage peaks which modify the risk for CF-related diabetes and meconium ileus. Candidates will be selected based on biological plausibility, using our group's extensive experience in CF pathophysiology. An optimal set of single nucleotide polymorphisms will be identified, and DNA from CF patient families will be genotyped. Genetic association and additional linkage analysis will confirm or exclude each candidate gene, as well as refine the linkage peaks. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK076446-02
Application #
7314125
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Hyde, James F
Project Start
2006-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$58,886
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

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
Green, Deanna M; McDougal, Kathryn E; Blackman, Scott M et al. (2010) Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients. Respir Res 11:140
Blackman, S M; Hsu, S; Ritter, S E et al. (2009) A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis. Diabetologia 52:1858-65
Blackman, Scott M; Hsu, Stephanie; Vanscoy, Lori L et al. (2009) Genetic modifiers play a substantial role in diabetes complicating cystic fibrosis. J Clin Endocrinol Metab 94:1302-9