GiM: Clinical Genetics Flashcards
Link between diabetes and genetics?
Familial forms (type 1). Genes mutated= glucokinase transcription factors. This affects the development and function of pancreatic b-cells.
What is pharmacogenomics?
Analysing entire genomes across groups of individuals to identify the genetic factors influencing responses to a drug.
What is pharmacogenetics?
Studying an individual’s genetic make up in order to predict responses to a drug and guide prescription.
What genetic fault results in Chronic Myeloid Leukaemia?
CML is caused by a translocation mutation between:
-a portion of chromosomes 9 and 22 (fusion of the abl gene from 9 with the BCR gene from 22)
This fusion gene is known as BCR/abl (on the Philadelphia chromosome) which triggers the uncontrolled production of white blood cells.
What does the drug Gleevec do?
The drug Gleevec blocks the action of the BCR/abl protein in patients with Chronic Myeloid Leukaemia. The production of white blood cells then returns to normal.
Examples of Autosomal Dominant Inheritance?
Myotonic dystrophy, Marfan Syndrome, Huntington disease.
Examples of Autosomal Recessive Inheritance?
Cystic Fibrosis, many metabolic disorders, Haemachromatosis, Sickle cell disease
Example of X-linked Inheritance?
Duchenne Muscular Dystrophy, Fragile X syndrome, Red/green colour blindness, Haemophilia.
No male to male transmission.
What is Lyonisation?
X-inactivation.
It is the process of random inactivation of one of the X chromosomes in cells with more than one X chromosome.
Occurs in early embryogenesis.
Skewed X-inactivation= random preference for ‘normal’ x-chromosome to be inactivated.
What is Penetrance?
The frequency with which a specific genotype is expressed by those individuals that possess it. (may alter with age eg Huntingtons by 80 years= 100% penetrance)
What is new dominant/ de novo mutation?
A new mutation that has occurred during gametogenesis or in early embryonic development.
The child is the first to be affected in their family and can pass on the mutation to their own children.
What is aneuploidy?
A gain or loss of chromosomes (can affect either autosomal or sex chromosomes). These conditions are usually caused by non-dysjunction during meiosis and can lead to monosomy or trisomy.
What is a) reciprocal translocation?
b) Robertsonian translocation?
a) reciprocal translocation= genetic material is exchanged between different chromosomes.
b) Robertsonian translocation= the short arms of 2 chromosomes are lost and the long arms fuse at the centromere to make a single large chromosome.
a) Which direction are DNA sequences written?
b) What does an extra -OH on C2’ in RNA mean?
c) How is DNA replicated in terms of 5’ and 3’ ends?
a) Written in a 5’ –> 3’ direction
b) This makes it self hydrolysed and less stable (transient)
c) 5’ has to be replicated in okazaki fragments, 3’ replicated continuously
What are the 3 components that make up genes?
- Exons (ends up in the spliced mRNA)
- Introns
- Regulatory sequences (promoters, enhancers, locus control regions)
