Week 2 Flashcards
(44 cards)
—————- : a type of gene mutation in which the addition or deletion of one or more nucleotides causes a shift in the reading frame of the codons in the mRNA, which may lead to the alteration in the amino acid sequence at protein translation.
frameshift
Synonymous vs Non-Synonymous Substitution
- Synonymous –> silent (no effect on the amino acid )
- Non-synonymous –> Missense / nonsense (alters an amino acid which may produce a malfunctioning protein)
Nonsense vs missense mutation
Missense: substituation of a different amino acid into the amino acid sequence as a result of the nucleotide change
Nonsense: a point mutation which introduces a premature stop codon into mRNA sequence as a result of a nucleotide change.
what type of mutation causes Cystic Fibrosis?
Loss of fxn on the CFTR gene
what type of mutation is Duchenne muscular dytrophy (DMD) + Mode of inheritance
Type: out-frame mutation on the Dystrophin gene
mode : X-linked recessive (XLR)
Clinical presentations of Duchenne Muscular dystrophy (DMD)
1) Progressive muscle weakness
2) Wheelchair dependency
3) delayed motor milestones
4) cardiomyopathy
Clnical case
- 3-year-old boy
- Unable to run
- Muscle weakness
- Uncle died at age 21 and was on wheelchair
- Muscle biopsy
- Loss-of-function mutations in the Dystrophin gene (X-linked recessive)
- Mostly deletions of part or all of the gene
Disorder?
DMD - Duchenne muscular Dystrophy
Give an example of a disease caused by an inframe mutation (Gain of function mutation )
Beckers muscular Dystrophy
*some Dystrophin produced
clinical case:
* 6-year-old girl
* Multiple fractures/ minor trauma
* Blue sclera
* Abnormal structural integrity of bones
disease?
Osteogenesis Imperfecta (OI type IV)
Osteogenesis Imperfecta are caused by Altered structures of ? what type of mutation?
type: Dominant negative mutations
altered sturctures: pro α1(1)/ pro α2(1) chains/ Integration into triple helix
Type of mutation of Type I OI
Nonsense mutation
Type of mutation of Type II-IV OI
Missense, dominant negative
what syndrome is missing chromosome 4?
Wolf-Hirschhorn syndrome, Huntington chorea, Achondroplasia
Why do people with Wolf-Hirschorn (WHS) do not develope Huntington Disease or Achondroplasia ?
Becasue they 4p gene is delelted at different regions
Wolf-Hirschhorn syndrome (4p-)
HD (4p16.3)
Ach- FGFR3 (4p16.3)
Type of mutation of Osteogenesis Imperfecta (COL1A1 vs COL1A2)
COL1A1–> dominant negative
COL1A2 –> loss of function
Clinical case:
* 4-year-old boy
* Unusual skin pigmentation- 7 Café-au-lait macules > 5mm
* spine –> mild scoliosis
* Optic glioma
* Multiple Lisch nodules (iris hamartomas)
Disroder?
NF1 - Neurofibromatosis Type 1
Lisch nodules
————- The fraction/proportion of individuals with a genotype known to cause a disease who have any signs or symptoms of the disease
- Does not involve severity of the disease
- Can be aged-dependent
Penetrance
MoI + type of mutation of Hereditary Breast and Ovarian cancer?
*MoI : mode of inheritance
MoI : Autosomal dominant inheritance (AD)
mutations in : BRCA1/2
* Reduced penetrance (Females have 87% risk , males have 20% risk)
Reduced penetrance typically described for autosomal [dominant/recessive] diseases
Dominant
Note:
can also apply to recessive ones (e.g.haemochromatosis)
Autosomal recessive disease w/ Reduced penetrance
Haemochromatosis
MoI of Huntington disease
Autosomal dominant
cause of Huntington disease
CAG trinucleotide repeat expansion in HTT gene
(ON an EXON)
CF of Huntington disease
Motor:
involunary –> chorea, rigidity, dystonia
Voluntary –> Clumsines, dysarthria, visual gaze
Cognitive: global decline in cognitive abilities
Psychiatric: depression, personality changes (bioplar), psychosis
Mean age of onset: late 30’s-40’s (Anticipation is observed)
Triade of clinical findings: motor, cognitive, Psychiatric
Normal CAG count?
6-26 repeats
* no risk of developing HD and no known risk to children
