Genetics

Question 1

What’s the chance of being carrier in AR condition

Answer 1

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

Question 2

CF carrier frequency

Answer 2

1/25
and 1/2500 babies are affected
1/25 x 1/25 x 1/4

Question 3

Haemochromatosis carrier frequency is 1/10

What’s the chance of a the baby being affected?

Question 4

What’s the penetrance for BRCA 1?

Answer 4

80%

Question 5

Expressivity vs penetrance

Answer 5

Penetrance is black and white
Expressivity is a spectrum

Question 6

TS
does it have mosaicism

Answer 6

high level of mosaicism (5%)

Question 7

what’s compound heterozygous?

Answer 7

2 different mutation on same gene

Question 8

what’s locus heterogeneity?

Answer 8

The presence of variants at different gene loci that cause the same or similar phenotypic expressions of a disease or condition.

Question 9

What do microRNA do?

Answer 9

control breakdown of RNA

Question 10

which position in the codon is least important

Answer 10

third

Question 11

Karyotype

Answer 11

Chromosomal testing
can detect: polyploidy, aneuploidy, translocation, inversions, rings
copy # variants in the size of 4-6Mb cannot detect very small CNV

Question 12

FISH

Answer 12

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

Question 13

Microarray

Answer 13

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

Question 14

PCR gene testing

Answer 14

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

Question 15

Sanger sequencing

Answer 15

Gene testing

gold standard test for one gene

• low error rate
• very few variants found

Example:
CFTR
FBN1
NF1
RB1

Question 16

Genomic testing (next generation sequencing)

Answer 16

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

Question 17

First line test for imprinting disorders

Answer 17

MS- MLPA