Allele: One of the alternative forms of a gene that may occur at a given locus on a chromosome.1
Apical cell membrane: The part of the cell membrane that faces the lumen, or extracellular cavity.2
Codon: A specific sequence of 3 consecutive nucleotides that is part of the genetic code and that specifies a particular amino acid in a protein or starts or stops protein synthesis.1
Complex alleles: Two or more mutations within the same allele (i.e., in cis).3
Conductance: The rate at which ions move through open CFTR protein channels.1,4,5
Gating: The opening and closing of the CFTR protein channel, which controls the transport of ions through the cell membrane; also referred to as open probability.1,4,5
Intron: A polynucleotide sequence in a DNA or RNA molecule that does not code information for protein synthesis and is removed before translation of mRNA.1
Modifier gene: A gene that affects the phenotypic expression of another gene.3
Mucociliary clearance: The movement of the mucus covering of the respiratory epithelium by the beating of cilia (tiny hair-like projections). Mucociliary clearance protects the airways by sweeping the mucus and trapped particles (bacteria, pollen, dust, etc.) from the lung.4
Open probability: The fraction of time that a single CFTR protein channel is open and transporting ions, also known as "gating."5,6
Polythymidine (Poly-T) tract: Sequence of thymidines located on intron 8 of the CFTR gene. Variation in length of the poly-T tract (5T, 7T, 9T) affects splicing and may result in a reduced amount of functional CFTR protein. When found on the same allele (in cis) as another CFTR mutation, it can influence the disease expression of that mutation.7
Ribosome: A cellular particle made of RNA and protein that serves as the site for protein synthesis in the cell. The ribosome reads the sequence of the mRNA and using the genetic code, translates the sequence of RNA bases into a sequence of amino acids.8,9
Splicing: The process by which introns in an RNA transcript are removed and exons are joined to form functional mRNA.1,8
Stop codon: A genetic codon in mRNA that signals the termination of protein synthesis during translation.1
Trafficking: The process of moving mature proteins from one compartment to another; in the case of CFTR, to the cell surface.10,11
Transcription: The process of making RNA from a gene sequence.8,9
Translation: The process of decoding mRNA to a sequence of amino acids during protein synthesis.8,9
Turnover: A process in the normal protein life cycle by which proteins are degraded and replaced.1,12
- US National Library of Medicine/NIH National Institutes of Health. MedLine Plus Medical Dictionary. http://www.merriam-webster.com/medlineplus. Accessed October 20, 2014.
- Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352(19):1992-2001.
- Castellani C, Cuppens H, Macek M, et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008;7(3):179-196.
- Orenstein DM, Spahr JE, Weiner DJ. Cystic Fibrosis: A Guide for Patient and Family. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012.
- Wang W, Linsdell P. Conformational change opening the CFTR chloride channel pore coupled to ATP-dependent gating. Biochim Biophys Acta. 2012;1818(3):851-860.
- Sheppard DN, Rich DP, Ostedgaard LS, Gregory RJ, Smith AE, Welsh MJ. Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties. Nature. 1993;362(6416):160-164.
- Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet. 1993;5(3):274-278.
- Strachan T, Read AP. Chapter 1: DNA structure and gene expression. In: Human Molecular Genetics. 2nd ed. New York, NY: Wiley‐Liss; 1999. http://www.ncbi.nlm.nih.gov/books/NBK7585. Accessed October 20, 2014.
- National Institutes of Health. National human genome research institute. Talking Glossary. http://www.genome.gov/Glossary. Accessed October 20, 2014.
- National Library of Medicine. Reference.MD. U.S. Government National Institutes of Health. http://www.reference.md/files/D021/mD021381.html.updated June 6, 2012. Accessed October 20, 2014.
- Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration. 2000;67(2):117‐133.
- Ward CL, Kopito RR. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. J Biol Chem. 1994;269(41):25710-25718.