Genetics Flashcards
(34 cards)
What is gonadal mosaicism?
- Occurs when precursor germline cells to ova/sperm are a mixture of 2 or more genetically different cell lines (due to errors in mitosis).
- One cell line is normal and the other is mutated.
What does mosaicism mean?
“Mosaicism” means a combination of cells.
Some have normal genes and chromosomes.
Some have mutated genes or chromosomes.
- If someone has germline mosaicism this means that some of their egg or sperm cells are normal and some contain a specific genetic mutation or chromosome problem.
Is the parent affected by germline/gonadal mosaicism?
The parent is healthy as the genetic change is only in the germline so all other cells are unaffected (have the usual/normal genetic components) but the foetus may have genetic diseases.
What increases the incidence of gonadal mosaicism?
- The incidence increases with advancing paternal age.
Where is gonadal mosaicism commonly observed?
- More common in males.
- Can be observed with ANY inheritance pattern but most commonly autosomal dominant and X-linked.
- Observed in a number of conditions e.g. osteogenesis imperfecta and Duchenne’s muscular dystrophy.
When is germline mosaicism usually confirmed?
Germline mosaicism is usually only confirmed if parents have more than one child with the
same genetic or chromosome disorder when both parents are not affected or carriers of
the condition.
N.B. Conditions that are inherited by means of germline mosaicism are often mistaken as being the result of de novo mutations (occurs for the first time in the family and not due to mutated genes/chromosomes in either parent).
List 4 examples of diseases with genetic causes.
Genetic- individually rare but cumulatively enough to have regional genetic services:
- Down’s Syndrome.
- Cystic Fibrosis.
- Huntington Disease.
- Haemophilia.
List 4 examples of diseases with multifactorial causes.
Multifactorial- main causes of diseases in devleoped countries:
- Spina Bifida.
- Cleft Lip/Palate.
- Diabetes.
- Schizophrenia.
List 4 examples of diseases with environmental causes.
Environmental- main causes of disease in 3rd world and A&E (genetics can play a small role):
- Poor diet.
- Infections.
- Drugs.
- Accidents.
What is autosomal dominant inheritance?
Only 1 copy of the mutant gene is required for the individual to be affected so the disease manifests in the heterozygous state.
- Males and females affected in equal proportions.
- Affected individuals in multiple generations.
- Transmission by individuals of both sexes to both sexes.
For what reasons might both parents be unaffected (in relation to an autosomal dominant condition)?
3 main reasons:
- Most commonly, they don’t have the genes for it due to gonadal mosaicism.
- Sometimes the mother has reduced penetrance.
- Sometimes the mother has variable expression i.e. the disease is there but not expressed clearly.
What chance is there that an offspring inherits an autosomal dominant condition from 1 affected and 1 non-affected parent?
As only 1 defective gene is required, there is a 50% chance of offspring having the condition.
What type of inheritance is responsible for male-to-male transmission?
The only way to pass on disease from male to male is by autosomal dominance inheritance- so if any male-to-male transmission seen, it is this form of inheritance.
What is an example of autosomal dominant inheritance?
Huntington’s disease.
What is autosomal recessive inheritance?
Both/2 copies of the mutant gene required for the individual to be affected so the disease manifests only in the homozygous recessive state.
- Males and females affected in equal proportions.
- Affected individuals only in a single generation.
- N.B. Recessive disorders most common in families where parents are related i.e. consanguineous.
What chance is there that an offspring inherits an autosomal recessive condition from 2 carrier parents?
2 defective genes are required, so:
- 25% chance of offspring have the condition.
- 50% chance of offspring being carriers.
- N.B. Healthy siblings have 2/3 chance of being carriers.
What is an example of autosomal recessive inheritance?
Cystic fibrosis.
What is cystic fibrosis?
A chronic condition affecting mainly the lungs and the gut, variable presentation.
What is the incidence of cystic fibrosis?
Incidence of 1 in 25,000.
N.B. The most common autosomal recessive condition affecting whites in the U.K.
What is the population carrier frequency for cystic fibrosis?
1/25 i.e. 25% of the population are carriers.
N.B. If both parents are carriers, you have a 50% chance of being a carrier.
How does the calculation vary when looking at probabilities for the risk of being a carrier?
The already affected child is disregarded- e.g. with the autosomal recessive condition, if you get:
- 1 unaffected offspring.
- 2 carrier offspring.
- 1 affected offspring.
The probability of being a carrier is not 1/2 as the affected individual is disregarded and the probability is actually 2/3.
What is X-Linked A.K.A. Sex-Linked inheritance?
Caused by a mutation in genes on the X chromosome.
What are examples of X-Linked inheritance?
Haemophilia and Duchenne’s muscular dystrophy.
What scenario never involves X-Linked inheritance?
X-linked can never involve male-to-male transmissions so can never be passed from father to son.
- This is because sons always get their X chromosome from their mother.
- N.B. Males= XY, females= XX.
