Genetics Flashcards
What’s the chance of being carrier in AR condition
Sibling of an affected person has 2/3 chance of being a carrier
Sibling or parent of a carrier has 1/2 chance of being a carrier - because we assume that only one parent is a carrier
CF carrier frequency
1/25
and 1/2500 babies are affected
1/25 x 1/25 x 1/4
Haemochromatosis carrier frequency is 1/10
What’s the chance of a the baby being affected?
What’s the penetrance for BRCA 1?
80%
Expressivity vs penetrance
Penetrance is black and white
Expressivity is a spectrum
TS
does it have mosaicism
high level of mosaicism (5%)
what’s compound heterozygous?
2 different mutation on same gene
what’s locus heterogeneity?
The presence of variants at different gene loci that cause the same or similar phenotypic expressions of a disease or condition.
What do microRNA do?
control breakdown of RNA
which position in the codon is least important
third
Karyotype
Chromosomal testing
can detect: polyploidy, aneuploidy, translocation, inversions, rings
copy # variants in the size of 4-6Mb cannot detect very small CNV
FISH
Chromosonal testing
Simple and quick
Targeted to region of choice
detects smaller chromosome deletion/duplications not visible on karytypes i.e Di Geroge syndrome, William syndrome
cannot detect very small CNV
Microarray
Genome wide high resolution chromosome analysis
Detects:
Small CNV that cannot be detected by karyotype or FISH
Copy neutral changes: SNP based platform only
- long continuous stretches of homozygosity (LCSH), uniparental disomy
cannot detect rearrangement (translocations) or sequence variant in genes
PCR gene testing
method of copying a target region of DNA
Components:
- DNA target template
- Two primers for 3’
- DNA polymerase (synthesis of new DNA strand)
- dNTPS
- Buffer solution
Sanger sequencing
Gene testing
gold standard test for one gene
- low error rate
- very few variants found
Example:
CFTR
FBN1
NF1
RB1
Genomic testing (next generation sequencing)
Includes:
Targeted gene panel sequencing
WES
WGS
Mostly detects single nucleotide variants (SNV) in genes
- useful for genetically heterogenic conditions
Limitations:
- CNVs:
>exon/whole gene deletions/duplications
i.e DMD has high deletions/duplications
these are not detected on WED or targeted panels, but can detected on WGS or MLPA
- nucleotide repeat expansions are not detected by all genomic testing
>needs southern blot or triple primed PCR
>example of disease:
fragile X: CGG FRAX
HD: CAG, HTT
Friedreich ataxia GAA (intron)
MD: CTG DMPK
MLPA:
- quatitive test
Southern blot:
- separated by size
- detects deletions, duplications, nucleotide repeats
- used for 100 basepair to 20kb
- EXPENSIVE
First line test for imprinting disorders
MS- MLPA
