Atypical mendelian inheritance Flashcards
Define genetic anticipation
increasing severity and earlier age of onset of a disease in successive generations
List examples of diseases with genetic anticipation
- Huntington disease
- Fragile X
- Myotonic dystrophy
What are the common features of diseases with genetic anticipation?
All include neurological symptoms
the presence of tract of trinucleotide repeat units that lie within, or adjacent to a disease associated gene
What is the common trigger for diseases with genetic anticipation?
Expansion of the trinucleotide tract beyond a certain size, resulting in it becoming a pathogenic mutation
What is pseudodominant inheritance
Disease appears to be autosomal dominant, but actually autosomal recessive
What is the common cause of pseudodominant inheritance
A high carrier frequency in the population, making it common for affected individuals to have affected children
Name an example of a pseudodominant inherited disease
- Glibert syndrome (jaundice)
Describe mitochondrial inheritance
only inherited from the mother but to variable extents
Describe the mitochondrial genome
- much smaller genome
- circular
- 37 genes
- no introns
What are the commonly affected regions with mitochondrial disorders?
- muscle
- brain
- eyes
How do mitochondrial disease occur?
Defective funtion of the mitochondiral respiratory chain
Name an example of a mitochondrial disorder
Leigh’s disease
- MT-ATP6 gene mutated in mitochondrial DNA
- product = ATP synthase
Define mosaicism
genetic abnormality that arises during mitosis, post-fertilisation
N.b individuals possess both a normal cell line, and a genetically abnormal cell line
What is the clinical consequence of mosaicism?
only some of the individuals cells may exhibit the phenotypic characteristics of a particular genetic condition
How might offspring inherit the mosaicism mutation?
If the mosaicism is present in the gonads
N.B - the mutation would then be present in all of the child’s cells
Define gonadal mosaicism
Phenotypically healthy individual may posses a genetic abnormality that is present in a proportion of their germ cells
How does gonadal mosaicism affect offspring?
A disease may be present in more than one of the children of a clinically unaffected individual
What are modifier genes?
genetic varients that can affect the manifestation of a disorder, such as
- age of onset
- range or severity of symptoms
- rate of disease progression
What are susceptibility genes?
Those that alter the liability to develop the condition rather than altering the phenotype of the disease
What processes may products of modifier genes alter?
- splicing
- transcription
- translation
- transport
- post-translational modification
- secretion
- activation
- degradation
What is digenic inheritance?
Clinical condition that may arise from the interaction of different genes
What is pseudoautosomal inheritance?
mutations of genes within the pseudoautosomal regions of the X and Y chromosome are inherited in an autosomal-like fashion
What is the pseudoautosomal region of the X and Y chromosomes
The area in which recombination of the X and Y chromosomes can only take place
How do mutations of genes within the pseudoautosomal regions of the X and Y chromosomes occur?
The 29 genes in this region escape X inactivation and are present on both the X and Y chromosomes
