L73 – Genetics of Respiratory Diseases Flashcards
(40 cards)
Effect of cystic fibrosis on airways?
Buildup of thick, sticky mucus in lungs
> > clogging, infection of bronchial passages
> > impede breathing, destroy lungs
Effect of cystic fibrosis on pancreas?
pancreatic insufficiency,
diabetes
occlusion of ducts prevents pancreas from delivering critical digestive enzymes to bowel
Effect of cystic fibrosis on skin?
malfunctioning of sweat glands
|»_space; perspiration contains excessive salt
Which chromosome is the CF gene located on?
7
What does the CF gene translate?
CFTR
Cystic fibrosis transmembrane conductance regulator protein
What does CFTR do?
Membrane protein > controls passage of chloride ions in and out of the cells
What type of mutation occurs in CF?
Deletion of phenylalanine in position 508 in CTFR
What are the domains of CFTR?
TMD-1, TMD-2 = transmembrane domains
NBF-1, NBF-2 = nucleotide-binding folds
R = regulatory domain
What are the 2 ways of CFTR defect ?
Mutation > CFTR in membrane but doesnt work
Mutation > completely missing CFTR
Explain how CFTR normally functions in sweat glands?
Cells secrete water into duct from tangled end of gland
As sweat rises towards skin, cells lining UPPER DUCT reabsorb Na+, Cl-, other molecules
> > Cl- move from sweat into cells, create electrical gradient > draw Na+ into cell
> > Decrease salt conc. in sweat
Explain the normal function of CFTR in pancreas?
Normally: CFTR pumps Cl- into duct
» water slurry follows (osmosis)
> > flows out into intestine carrying digestive enzymes
Explain the defective function of CFTR in pancreas?
CFTR is missing»_space; Cl-, water stay in cells (no slurry to carry enzymes away)
> > enzymes begin to digest pancreas itself
inflammation
thick mucus plugs duct (pancreatic insufficiency)
What is the treatment for CF lungs?
inhale recombinant human deoxyribonuclease I (Dornase Alfa) to reduce mucus viscosity
Mechanical suction
What kind of gene defect is CF?
Single gene defect
Autosomal recessive
What are the chances of carrier, affected and unaffected when CF carrier x CF carrier?
carrier x carrier
25% unaffected,
50% carriers,
25% affected
What are the chances of carrier, affected and unaffected when CF affected x CF carrier?
50% carriers
50% affected
Rank the frequency of carrier and carrier of White, Asian , Black and Hispanic?
White > Hispanic > Black > Asian
Why CF mutation exists in such high frequency?
heterozygote advantage against diarrhea (e.g. cholera), pulmonary tuberculosis, thalassemia
What is the Molecular diagnosis of CF?
PCR: specific primer against CF gene
» stain DNA by ethidium bromide
» visualize as a band
What are the hallmarks of a multifactorial disease? (2)
Healthy parents can have son / daughter with
asthma
A (more) severely affected parent is (more) likely to
produce an affected child
Explain in multifactorial disease, why 2 affected parents are more likely to produce an affected child?
Explanation:
assume liability for traits is additive
» one disease gene with large effect vs. multiple genes (small proportion gets all the good / bad genes)
> > Continuous / quantitative distribution of severity
List some common Non-Mendelian trait / disease?
intelligence, height, asthma, hypertension, diabetes mellitus, cleft lip, cleft palate
> > regression to mediocrity
What does polygenic mean?
multiple genes:
Each of the genes has a relatively small effect on the phenotype
> these traits/ diseases reflect the cumulative effect
of genetic variation at these loci
What is the difference between polygenic and multi-factorial?
multi-factorial:
Multiple genes interplay with environmental factors
polygenic:
Determined by many genes at different loci, without the influence of the environment
