Medical genetics - consequences of genomic alteration Flashcards
What are the four major categories of genetically determined diseases?
- Single gene disorders
(mutation to only one gene eg B thalamessiamia) - Chromosome disorders
(mutation/change to a whole chromosome eg downs syndrome) - Multifactorial genetic disorders
(result from the interaction of multiple genes eg diabetes) - Somatic cell disorders
(mutations in somatic cells ie after the fusion of the sperm and egg. most common example is cancer. these cannot be inheretid)
what does polymorphism mean?
Polymorphism generally means variation. It refers to the natural variation that is present in the population (excluding the muations) of which natural selection can act upon.
What are SNP’s?
SIngle nucleotide polymorphisms =
is a variation in a single nucleotide that occurs at a specific position in the genome
These are very helpful in tracing disease causing gene sequences as they act as little “red flags”
What are the different types of mutations?
Silent
- single base change that still produces same amino acid
Missense
- single base change that does produce a different amino acid but may or may not actually produce a different phenotype
Nonsense
- single base change that produces a stop codon as opposed to an amino acid
Frameshift
- insertion of deletion of bases that alters all of the following triplets/codons and hence changes all of the following amino acids
Splice donor/ acceptor
- alteration of sequences for accurate splicing of introns
Explain the difference between mutations in somatic cells compared to mutations in germline cells
Mutations that occur in somatic cells (non gamete forming cells) are limited to that individual and cannot be passed on.
Mutations that occur in germline cells (cells that form the gametes) have potential to be passed on to further generations.
What are the two phenotypic consequences of a mutation?
Gain of function mutation -
Produce an increased amount or increased activity of the product
Loss of function mutation -
Produce a reduced amount or a reduced activity of the product
What is a null allele? (resulting from a loss of function mutation)
Complete abscence of a gene product or complete abscence of the normal function of the gene product results from a null allele
What is a dominant negative effect? (resulting from a loss of function mutation)
Occurs when the product of the abnormal allele interferes with the product of the normal allele.
What is the likelihood that an offspring will have a autosomal dominant condition if one of the parents has it?
50% chance.
The unaffected parent will always only pass on the recessive allele so then it is up to the affected parent as to whether they pass on the dominant or recessive allele (50:50 as to which one).
What is the likelihood that an offspring will inherit an autosomoal reccessive condition from two heterozygous parents?
25% chance.
What is the likelihood that the offspring will be unaffected but will be a carrier of a autosomal recessive condition if both the parents are heterozygous?
50% chance.
What is lyonisation?
Early on in embryonic development one of the X chromosomes in each somatic cell of a female is randomly inactivated. This creates a level playing field by ensuring that there is only one active X chromosome in both male and female cells. Because it is a random process, some female cells may have an active X cell from their mothers while others may have an active X cell from their fathers.
In an X linked recessive disorder, what is the likelihood that the son will be affected? what is the likelihood that the daughter will be affected?
50% chance.
The son only inherits the X chromosome from the mother. If the mother is Heterozygous (a carrier of the X linked condition) then there is a 50:50 chance as to whether they will inherit the dominant or recessive allele.
The daughter will inherit an X chromosome from both the father and the mother. If the father is unaffected and the mother a carrier than once again there is a 50:50 chance as to whether the daughter inherits the recessive allele of the dominant allele. However because of the dominant allele from the father, they cannot be affected with the disorder - they will only be a carrier.
Is an X linked dominant disorder more common in males and females? What effect does lyonisation have?
Females - because they inherit two X chromosomes so the chance of inheriting a dominant allele is greater.
Lyonisation means that the effect is often more mild and variant in females than males.
What distinguishes autosomal dominant from X linked dominant?
None of the sons will be affected but all of the daughters will be affected.
