Forms of Inherited Disease Flashcards
What are 3 types of genetic diseases that are inherited in different ways?
Monogenic (Mendelian)
Polygenic
Chromosomal disorders
What does congenital vs acquired mean?
Congenital = present at birth Acquired = not inherited or present at birth
What is a polymorphism?
An allele variant that is present in more than 1% of the population
What is a variant?
Any loci that has more than one possible allele within the entire population, even if in less than 1%
What are the features of a gene that undergoes Mendelian inheritance?
The gene has two copies (maternal and paternal)
The copies of the gene separate into two gametes
The copies of the gene segregate independently
What are the features of an autosomal dominantly inherited disease gene? In terms of -penetrance -expressivity -onset -gain/loss of function
Tends to have reduced penetrance
Variable expressivity
Late onset (onset after the affected individual has had children)
Usually ‘gain of function’ - only need one allele to gain function for there to be a problem
Example of an autosomal dominant condition
Huntington’s Disease
How can a loss of function mutation ever be dominant?
Haploinsufficiency
One correctly functioning allele is not enough to maintain normal function
Features of an autosomal recessively inherited gene
In terms of
-family history
-gain/loss of function
Often no family history
Can be homozygous of compound heterozygous
Usually ‘loss of function’ mutations
Example of an autosomal recessive condition
Phenylketonuria (PKU)
What does homozygous vs compound heterozygous mean?
Homozygous = Same mutation inherited from both parents
Compound heterozygous = Different mutations inherited in each allele, both cause same problem
Features of an X-linked recessive condition
No male-to-male transmission
Mainly affects males as they only have one X chromosome, female carriers less affected
Example of an X-linked recessive condition
Duchenne Muscular Dystrophy
Features of an X-linked dominant condition
Usually only found in females, as it is usually lethal in males so they do not survive
Example of an X-linked dominant condition
Rett Syndrome
Causes delayed development, autism, lack of speech, lack of ability to walk
What is X-inactivation?
Females have two X chromosomes, so one of them is inactivated, to prevent twice the amount of gene products
Which one is inactivated in random, but all descendants of that cell will have the same one inactivated
This leads to the pattern on female tortoiseshell cats
What does hemizygous mean?
One copy of a chromosome
e.g. males are hemizygous for the X chromosome
Name examples of non-mendelian inheritance
De novo mutations Mitochondrial inheritance Epigenetic inheritance Mosaicism Trinucleotide repeat disorders
What is mosaicism?
The mutation is not present in every genetically related cell
Can occur if a mutation occurs during early mitosis of a zygote
e.g. If it occurs during the first division, 50% of all cells will be affected
What is germline mosaicism vs somatic mosaicism?
Germline mosaicism = a mutation in the germline cells means that some gamtes carry the mutation and some don’t. Disease may occur in child and siblings
Somatic mosaicism = mutation arises post-fertilisation
