Lecture ILOs

Question 1

Autosomal dominant inheritance features

Answer 1

Vertical pattern
Heterozygous affected
Males and females in same generation affected
Male to male transmission (not x-linked)

Question 2

Modifier genetic variants definition

Answer 2

Other genes the impact the severity of a condition

Question 3

Autosomal recessive pattern

Answer 3

Horizontal pattern
Males and females affected equally
May be consanguinity in family

Question 4

X-linked recessive inheritance features

Answer 4

Knights move pattern
No male to male transmission
Mostly males affected

Question 5

X-linked dominant inheritance features

Answer 5

Never male to male transmission
Vertical patterns
Male to female transmission= all affected
Female to female transmission= 50% affected
Sex ratio 2F:1M

Question 6

Genetic anticipation definition and example

Answer 6

Increased severity and earlier age of onset in successive generations

Eg. Huntington’s, fragile x syndrome, myotonic dystrophy

Question 7

Techniques for Detection of point mutations

Answer 7

Sanger sequencing
Next gen sequencing
Allele specific PCR (ARMS)- known point mutations

Question 8

Techniques for detection of sub microscopic duplications/deletions

Answer 8

MLPA (known positions)

Chromosomal micro-array (genome wide)

Question 9

Techniques for rapid detection of aneuploidies

Answer 9

Quantitative fluorescent PCR

Question 10

Describe the pathology and presentation of Huntington’s disease

Answer 10

Clinical presentation:

• onset 30-50
• progressive chorea, dementia, psychiatric symptoms

Pathology:

• autosomal dominant with genetic anticipation
• length mutation in HTT gene
• > 35 CAG repeats
• insoluble protein aggregates

Question 11

Pathology and presentation of myotonic dystrophy

Answer 11

Clinical aspects:

• progressive weakness
• myotonia
• cataracts

Pathology:

• autosomal dominant with genetic anticipation
• length mutation in CTG repeat
• abnormal DMPK mRNA

Question 12

Pathology, diagnosis of cystic fibrosis

Answer 12

Autosomal recessive
Recurrent lung infections, exocrine pancreas insufficiency
CFTR mutation —> defective Cl channel —> increased thickness of secretions

Diagnosed by trypsin level, DNA testing, sweat testing

Question 13

Duchenne muscular dystrophy

Answer 13

X-linked recessive
Xp21 gene mutation
Increased serum creatinine kinase

Onset 3yo
Wheelchair by 12
65% deletion
Moist out of frame
No dystrophin made

Question 14

Becker muscular dystrophy

Answer 14

X-linked recessive
Onset 11yo
Wheelchair later if at all
85% deletions
In frame
Some dystrophin present

Question 15

Presentation and complications of neurofibromatosis-1

Answer 15

Common:

• cafe au lait macules
• short stature
• neurofibromas
• macrocephalic

Complications:

• hypertension
• scoliosis
• tibial fractures
• tumours

Question 16

Common chromosomal abnormalities

Answer 16

Downs= trisomy 21 (14:21 translocation)
Edwards= trisomy 18
Patau= trisomy 13

Question 17

Examples of x-linked dominant

Answer 17

Vit D resistant rickets
Incontinentia pigment
Rhett syndrome

Question 18

Features of familial cancer

Answer 18

More than 1 individual in same family affected by similar cancers
Cancers at repeated sites with early age on onset

Multiple primaries, early age of onset

Question 19

Genetic mutations in familial cancer

Answer 19

BRCA1,2
TP53
PALB2
PTEN

Question 20

Pseudodominant inheritance

Answer 20

Inheritance pattern appears autosomal dominant even though recessive

Occurs if carrier frequency is high or if there is consanguinity

Ie. Gilbert syndrome

Question 21

Examples of colon cancer family syndromes and genes affected

Answer 21

Hereditary non-poly posits colon cancer= MMR gene
Familial adenomatous polyposis= APC gene
MYH polyposis