(1) Introduction to genetics Flashcards
What is genetic counselling?
An education process that seeks to assist affected or at risk individuals to understand the nature of the genetic disorder, the nature of its transmission and the options open to them in management and family planning
What are the reasons for clinical genetics referral?
- affected child/adult for investigation or diagnosis
- family history of genetic disorder or condition with genetic component
- foetal loss/abnormality
- recurrent miscarriages
- strong family history of cancer
What are the aims of genetic counselling?
Give information
- inform people of the medical facts
- talk about treatment and prognosis
- explain inheritance
- discuss chance of happening again
Talk about choices
- whether to have genetic tests
- whether to have more children
- whether to have tests during pregnancy
How do you go about making a genetic diagnosis?
Family tree
- to detect a pattern of inheritance
Physical examination
- to give precise diagnosis
Genetic tests
- chromosomes (karyotype)
- genes (DNA testing)
What are the Mendelian/monogenic forms of hypertension?
Rare syndromes of hypo- or hyper- tension eg. pseudohypoaldosteronism, Liddle syndrome
Which genes are mutated in Mendelian/monogenic forms of hypertension?
Those involved in renal salt balance eg. ENaC, mineralocorticoid receptor gene
What are the Mendelian/monogenic forms of diabetes?
Familial forms (type 1), MODY
Which genes are mutated in Mendelian/monogenic forms of diabetes?
Glucokinase transcription factors
What are the Mendelian/monogenic forms of idiopathic epilepsy/migraines?
Familial epilepsies
Which genes are mutated in Mendelian/monogenic forms of idiopathic epilepsy/migraines?
Ion channels eg. KCNj10
What is Gefitinib?
“Iressa”
The first selective inhibitor of epidermal growth factor receptor (EGFR/HER1) tyrosine kinase domain
EGFR is over expressed in what?
In the cells of certain types of human carcinomas eg. non-small cell lung cancers
Mutations in the EGFR tyrosine kinase domain confer what?
Increased sensitivity to tyrosine kinase inhibitors such as gefitinib
What is the problem with gefitinib?
Effective in only 15% of patients with advanced NSCLC, the most common type of lung cancer
Give some examples of types of genetic tests
Genomic architecture
- cytogenetics
- array based techniques
Gene faults
- sequencing
- OLA assays
- MLPA tests
What are the advantages of testing for genetic disorders?
Early diagnosis
- early interventions
- eg. deafness
Carrier testing
- reproductive choices
Prenatal testing
- reproductive choices
What are the disadvantages of testing for genetic disorders?
- do you want to know you’re going to get cancer sometimes?
- screening might help
- no treatment eg. alzheimers
- affect insurance prospects?
What are the 2 categories of personalised medicine?
- pharmacogenomics
- pharmacogenetics
What is pharmacogenomics?
Analysing entire genomes, across groups of individuals, to identify the genetic factors influencing responses to a drug
What is pharmacogenetics?
Studying and individual’s genetic make up in order to predict responses to a drug and guide prescription
What is Gleevec?
A treatment for CML which is targeted at the novel fusion protein, the product of the translocation seen in CML.
Production of white blood cells usually returns to normal
What is the mutation in chronic myeloid leukaemia (CML)?
Translocation, portions of chromosomes 9 and 22 switch places
What does the translocation in CML result in?
Results in the fusion of the abl gene from chromosome 9 with the BCR gene in chromosome 22
What is the chromosome that carries the BCR/abl fusion gene called in CML?
The Philadelphia chromosome
What does the BCR/abl gene in CML code for?
A signalling protein that triggers the uncontrolled production of white blood cells
