Phenotypic Variability Flashcards
What are genetic and environment interaction?
-Underlying causes of disease are genetic important role for environment (e.g. factors external to the patient) in progress and outcome of the disease for each patient
What is Multiple Endocrine Neoplasia type 1 (MEN1)
-This is a disease which increases the carriers’ chance of developing adenomas in endocrine tissue
What causes MEN1?
-Caused by a mutation in the MEN1 gene, a tumour suppressor gene
How is MEN1 inherited? What is it impacted by?
- Condition inherited in an autosomally dominant
- Not all people with the mutation will develop the same types of adenoma or at the same time as a second event needs to happen to promote tumour formation so some develop many tumours at young age and others do not develop any tumours until v late in life
What is Hereditary haemochromatosis?
-This is an autosomally recessive gene
What is Hereditary haemochromatosis caused by?
-Caused by a mutation in the human homeostatic iron regulator protein (HFE)
What are the impacts of Hereditary haemochromatosis?
- This affects the way in which dietary iron is absorbed leading to excess iron absorption
- This can lead to a build up of iron in various organs and subsequent organ damage.
What are the different types of Hereditary haemochromatosis
- However only 10% of people with hereditary haemochromatosis have clinically relevant iron accumulation. Women are protected from iron accumulation due to menstrual bleeding. in men, the dietary load of iron can vary considerably and lower levels of intake are associated with improved disease prognosis.
- The natural history of many other diseases are affected by environmental factors for example cystic fibrosis and sickle cell disease can both be exacerbated by exposure to pollution
What are other genes and disease progression ?
- In addition to the presence of the disease gene the life course of a disease and the symptoms present are commonly modified by the presence of other genes
- These genes can either improve the condition or make the condition worse.
What are cystic fibrosis modifiers?
- number of gene variations that interact with the cystic fibrosis mutation to change the phenotype of the disease
- Variability of pulmonary phenotype and survival in cystic fibrosis, even among patients who are homozygous for the most prevalent mutation, delF508
- Variants of genes can modifiy cystic fibrosis
What are examples of cystic fibrosis modifiers?
- Patients withe the same homozygous delF508 mutation can be clasified as having either severe or mild lung disease.
- TGFB1, the gene encoding transforming growth factor beta-1, variants are associted with with the phenotype of severe lung disease.
What is FCGR2A?
- The risk of developing infections in cystic fibrosis can also be modified by a large number of gene variations
- Distinct from the Cystic fibrosis muation. One such gene is immunoglobulin Fc-gamma receptor II (FCGR2A) which if you have the variant can increase your change of developing a chronic Pseudomonas aeruginosa infection by 4 fold.
What is Von Hippel-Lindau Syndrome? ow is it inherited?
-Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors.
What does variation in CCND1 cause?
- Variation in cyclin D1 (CCND1) alters the phenotype of VHL
- The number of retinal angiomas is significantly higher in individuals harbouring the G allele compared with AA homozygotes. -Possession of 1 or more G alleles is associated with earlier diagnosis of CNS hemangioblastoma by almost 2-fold.
Are diseases just associated with a single gene?
- Some diseases are associated with only a single mutation for example sickle cell anemia
- Where as other disease can arise as the result of many mutations within the same gene.