Gene nomenclature Flashcards
How does whole exome sequencing work?
Fragments DNA and creates a matrix that only exons stick to
How can biochemical differences affect whole exome sequencing?
G-C enriches less well
some exons don’t stick as well
What is whole genome sequencing better for?
Copy number variants because there is no extra enrichment step
How do specific gene panels work?
Targeted enrichment chemistry
What are some rare instances where variants present in > 5% of the population are pathogenic?
Common pathogenic variants with low penetrance
How can segregation data provide evidence?
Variant causing issue in multiple families
No variant, no presentation
What does functional data consider?
structure of gene
site of mutation
hotspot mutations
biologically relevant transcript
alternative splicing
What mutations cause null variants?
framshift, nonsense
What is an example of a beneficial mutation?
pcsk9 receptor for chosterol decayed
- inactivating pcsk9 can be used to lower cholesterol
What does qfPCR look at?
short tandem repeats - can be used to confirm relationships
Half coloured in
Carrier
Give an example of a dominant disorder which can be more penetrant in one sex
Hypertrophic cardiomyopathy (some genes)
What determines the age of onset in Huntington?
quality of repeat
Baye’s theorem
population risk + individual evidence
When would you discount allele frequency in the population?
Recessive consanguinity
What is the carrier frequency in the population for recessive disorders?
1/20
What can X chromosome translocation cause?
Skewed X inactivation
Incorrect X inactivation can cause cell death, such as in…
Incontinentia pigmentii.
What does methylation cause?
chromatin condensation and histone acetylation
What base change does methylation cause?
C-G to T-G
Heteroplasmy
Different proportions of mutant mitochondria in different cells
Heteroplasmy examples
Retinitis pigmentosa
brain
heart
Allele
Gene copy
Wild type
Most common allele in population
What are the types of autosomal dominant mutations?
Dominant negative
Gain of function (activating)
Loss of function
Second hit
Quantitative variants
Variations in genome
Qualitative variants
Make abnormal proteins
Osteogenesis imperfecta type 1
Haploinsufficiency
Osteogenesis imperfecta type 2
Mutant collagen interferes with normal collagen
Hypomorphic alleles
Partial loss of function
(eg. CF)
