Genetics

Question 1

Alpha 1 antitrypsin gene

Answer 1

Mutation in the SERPINA1gene

Question 2

Hereditary motor and sensory neuropathy gene

Answer 2

PMP22

Question 3

Motor Neuron disease gene

Answer 3

SOD1

Question 4

Noonan gene

Answer 4

PTPN11

Question 5

Trisomy 18

Answer 5

Edward

Question 6

Trisomy 13

Answer 6

Patau

Question 7

Missense vs Nonsense Mutation

Answer 7

Question 8

Genetic conditions with cerebellar ataxia

Answer 8

CANVAS (Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome ) RFC1 gene
Spinocerebellar ataxia - FGF14 (late onset)
Fragile X

Question 9

Answer 9

Question 10

Answer 10

Question 11

Chromosomal microarray
- Used for
- Disadvantages

Answer 11

Used for deletion and duplication
Can’t pick up balanced translocations

Question 12

Answer 12

Question 13

Inheritance
G6PD

Answer 13

X linked

Question 14

Inheritance
Fragile X

Answer 14

X linked

Question 15

Inheritance
DMD/BMD

Answer 15

X linked

Question 16

Gene therapy for HD

Question 17

Omaveloxone for Frederich Ataxia

Answer 17

FA = GAA expansion FXN gene -> decreased frataxin -> decreased mitochondrial function (spinal cord + nerve + cerebellum)

Omaveloxone activates Nrf2 improves mitochondrial function

Question 18

Spinal muscular atrophy approved therapies

Answer 18

Itvisma once off gene replacement SMN1

Evrysdi risdiplam- oral small nucleotide Smn2 splicing modifier

Question 19

Bases present in RNA vs DNA

Answer 19

RNA - AUGC

DNA - ATGC

Question 20

Di George Syndrome Features

Answer 20

think midline structures

Cardiac defects (Tetralogy, interrupted aortic arch, truncus arteriosus)

Palatal abnormalities
Hypocalcaemia due to hypoplasia of parathyroids
Immunodeficiency due to thymic hypoplasia
Developmental delay

Question 21

Highest specificity for detecting single nucleotide variant ?

Answer 21

Sanger sequencing
(Still gold standard for confirmation e.g if mutation already detected on NGS / single mutation)

NGS better for multiple gene /mutations

Question 22

Southern blot when to use

Answer 22

After PCR for large trinucleotide repeat expansions e.g fragile X or myotonic dystrophy

Question 23

What can NGS not detect?

Answer 23

Trinucleotide repeats
Methylation

Question 24

FISH what can it detect

Answer 24

Chromosomal aneuploidy
Deletions/ duplications
Trinucleotide repeat

Quick within 24H
Cannot detect exonic deletions

Question 25

Which DNA base pair is methylated at 5’ position

Answer 25

C cytosine

Question 26

Which genomic technique for balanced translocations

Answer 26

Karyotype

Question 27

Which inheritance pattern is most effective for gene replacement therapy

Answer 27

Autosomal recessive

Question 28

Trinucleotide repeat condition CAG CAA CTG CGG Paternal vs maternal expansion

Answer 28

CAG Huntingtons (HTT), Spinocerebellar ataxia (various genes) , Kennedys syndrome (androgen receptor) CAA friedrichs ataxia (FXN) CTG myotonic dystrophy (DMPK) CGG fragile X tremor ataxia (FMR1) Paternal = CAG rest maternal