Lecture 21 - Inherited Disorders Flashcards
What are genetic mutations
Mutations within our genome can occur via mistakes introduced when the genome is being replicated, or during cell division
In heritable genetic diseases, these mutations are present in the germline
Where do most mutations that cause diseases occur
Coding sequence of protein coding genes
What are numerical chromosome abnormalities
Polyploidy refers to when a there is an extra set of chromosomes
Aneuploidy refers to when there is either an extra or missing single chromosome
What are recessive/dominant mutations
Both copies of a gene usually need be inactivated by mutations for a genetic disease to manifest i.e. the diseases display a recessive mode of inheritance.
Sometimes, mutation in one copy is sufficient for a given disease phenotype i.e. they display a dominant mode of inheritance. ‘Haploinsufficiency’ is an example
…or in other cases, the single mutated gene copy may have a ‘dominant negative’ effect. This can occur in Osteogenesis Imperfecta which can be caused by mutation in a single copy of a collagen-encoding gene
What occurs at a nondisjunction
Failure of attachment on one side of the spindle so both chromosomes end up on the same side
SLIDE 6+7
What is Trisomy 21
Extra copy of chromosome 21 leading to down syndrome
What are splice site mutations
Where there is a mutation in the splice acceptor site - affects the efficiency of the speciesome, like extension of t repeats or tg repeats . which can lead to diseases such as cystic fibrosis
Aberrant splicing and normal splicing
SLIDE 8
What is Mendelian (monogenic) inheritance
When referring to genetic diseases, Mendelian inheritance refers to the situation when the presence of mutation in a single gene is sufficient for disease manifestation
What is locus heterogeneity
One phenotype or disease can be caused by a mutation in any one of a number of genes (slide 14)
What is an example of phenotypic rescue
Slide 15
What is incomplete penetrance
Genetic mutations sometimes display a varying degree of penetrance i.e. they may not cause disease when otherwise expected
For example, according to the standard definition, a dominant mutation should result in 100% penetrance i.e. the disease will always manifest if a mutated allele is present (slide 17+18)
What is X mosaicism
Males possess one copy of the X chromosome and one copy of the Y chromosome
Females possess two of the X chromosome: this is one too many and one of them needs to be inactivated
This happens in the female early embryo and is a random process
This can lead to deviations from expected Mendelian predictions
What is mitochondrial inheritance
Though the mitochondrial genome (mtDNA) is very small, we do sometimes encounter disease that is caused by mutations in mtDNA genes
Inheritance of mitochondrial disease display their own characteristic patterns
Where is mtDNA inherited from
EXCLUSIVELY from the mother
Each egg contains thousands of mitochondria
What is Heteroplasmy
the presence of more than one type of organellar genome within a cell or individual
SLIDE 22
How does the threshold of mutated mitochondria affect different organs
Higher energy use of organ eg. brain or skeletal muscle takes a little amount of weakness to fail, whereas other organs have a higher threshold as they require less energy use
