Lecture ILOs Flashcards
Autosomal dominant inheritance features
Vertical pattern
Heterozygous affected
Males and females in same generation affected
Male to male transmission (not x-linked)
Modifier genetic variants definition
Other genes the impact the severity of a condition
Autosomal recessive pattern
Horizontal pattern
Males and females affected equally
May be consanguinity in family
X-linked recessive inheritance features
Knights move pattern
No male to male transmission
Mostly males affected
X-linked dominant inheritance features
Never male to male transmission
Vertical patterns
Male to female transmission= all affected
Female to female transmission= 50% affected
Sex ratio 2F:1M
Genetic anticipation definition and example
Increased severity and earlier age of onset in successive generations
Eg. Huntington’s, fragile x syndrome, myotonic dystrophy
Techniques for Detection of point mutations
Sanger sequencing
Next gen sequencing
Allele specific PCR (ARMS)- known point mutations
Techniques for detection of sub microscopic duplications/deletions
MLPA (known positions)
Chromosomal micro-array (genome wide)
Techniques for rapid detection of aneuploidies
Quantitative fluorescent PCR
Describe the pathology and presentation of Huntington’s disease
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
Pathology and presentation of myotonic dystrophy
Clinical aspects:
- progressive weakness
- myotonia
- cataracts
Pathology:
- autosomal dominant with genetic anticipation
- length mutation in CTG repeat
- abnormal DMPK mRNA
Pathology, diagnosis of cystic fibrosis
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
Duchenne muscular dystrophy
X-linked recessive
Xp21 gene mutation
Increased serum creatinine kinase
Onset 3yo Wheelchair by 12 65% deletion Moist out of frame No dystrophin made
Becker muscular dystrophy
X-linked recessive Onset 11yo Wheelchair later if at all 85% deletions In frame Some dystrophin present
Presentation and complications of neurofibromatosis-1
Common:
- cafe au lait macules
- short stature
- neurofibromas
- macrocephalic
Complications:
- hypertension
- scoliosis
- tibial fractures
- tumours
Common chromosomal abnormalities
Downs= trisomy 21 (14:21 translocation) Edwards= trisomy 18 Patau= trisomy 13
Examples of x-linked dominant
Vit D resistant rickets
Incontinentia pigment
Rhett syndrome
Features of familial cancer
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
Genetic mutations in familial cancer
BRCA1,2
TP53
PALB2
PTEN
Pseudodominant inheritance
Inheritance pattern appears autosomal dominant even though recessive
Occurs if carrier frequency is high or if there is consanguinity
Ie. Gilbert syndrome
Examples of colon cancer family syndromes and genes affected
Hereditary non-poly posits colon cancer= MMR gene
Familial adenomatous polyposis= APC gene
MYH polyposis
