Genetics Flashcards
What’s the most common environmental risk factor for the pathogenesis of COPD
smoking. Others include pollution, coal mining etc.
The reason is that A1AT is very suseptible to oxidative damage and smoking produces methionine which combines with A1AT resulting in methionine sulfoxide, this is made worse if overlaid on the background of someone with a genetic deficiency of A1AT.
Explain the role of alpha1 antitripsin in normal lungs and and pathogenesis of lung disease in its absence
The normal role of alpha1 anti-tripsin (A1AT) is to cleave peptidases such as elastase; secreted by PMNs which protects the lungs.
When there is a deficiency in A1AT the lungs are exposed to PMN damage by elastase (increase inflammation and attract more PMNs) and alpha1-anti-tripsin can be trapped in the liver causing liver damage.
Discuss the prevalence of alpha1 anti-tripsin deficiency and the genetic basis
1:1500-3500 europeans. Symptoms-non-treatable asthma or recurrent respiratory infections.
Young non smoker with emphysema
The genetic basis is the codominant expression of non functional or low functioning alleles that decrease levels of the protein
Define the term conformational disease and explain how it applies to the alpha1 anti-tripsin deficiency
The disease results from a blockage of protein processing and secretion (Z allele).
There are 3 alleles: M is wt, S (mod protein), and Z (low protein) these are co-dominantly expressed to produce various protein levels which can predispose someone to lung and liver damage especially if they have additional environmental risk factors such as smoking.
Discuss the prevalence of cystic fibrosis and its genetic basis
The rate of Cystic fibrosis is 1:25 caucasians
CFTR mutations impair the secretion of Cl- into the mucosal lining of the lungs.
Explain the role of CFTR in normal tissue and the parthenogenesis of disease in its absence
In normal tissue CFTR is secreted into the mucosal secretions that cover epithelial cells in the lungs and bronchi. It helps keep the mucous less viscous that allows the cillia to move it up and out of the airway, this removes bacteria and viruses and protects the lungs.
If this transport is defective the mucous becomes viscous and can not be moved by the cilia. infections become more common (pseudomonas) and those with the disease try to hack up this brittle mucous.
Discuss the goals of genetic testing
Unfortunatley there is no correlation to the type of genetic defect involving the CFTR gene and the phenotypic expression of disease. You just don’t know how severe the disease will be based on the mutation.
Goals: prevent lung infections remove mucus from lungs treat GI blockage (mucus there also) Provide adequate nutrition (absobtion of nutrients is affected in the gut)
