Genetics 2 Flashcards
De novo mutations common in what inheritance mode?
X-linked Recessive and Autosomal Dominant!
Consanguinity increases risk of what inheritance?
Autosomal recessive
Autosomal recessive Incidence formula?
Autosomal recessive carrier formula?
(Carrier frequency)2 x 4
Square root of (incidence / 4)
X-linked Dominant has what prominent feature?
All/Almost all females affected!
Male - fatal for men (male = hemizygous)
Imprinting is epigenetic phenomenon - what it means?
Pathogenesis of imprinting
No DNA changes - just modification of the gene function
via
- *Methylation and histone modification**
- methylate CPG islands
- Histone wrapped tightly around DNA - less transcription
imprinting occurs - what is expressed?
Monoallelic expression
Angelman and Prader-Willi syndrome - where does the imprinting occurs? what region?
Chromosome 15q12
3 possible mechanisms imprinting occurs?
Uniparental disomy
Microdeletion of one gene that is important
Imprinting defect - silence the gene that is important
Mitochondrial mutation affects what type of cell?
High energy dependent cells! - brain/heart/liver/endocrine
Neurofibromatosis-1 diagnostic criteria?
CAFE-SPOT
C-afe-au-lait = 6 or more A-xillary/inguinal freckling F-ibromas-neuro = 2 or more E-ye - Lisch nodules = 2 or more S-keletal osseous lesion ( long bone) P-ositive family history/pedigree O-ptic Tumor glioma = Carboplatin as tx
Neurofibromatosis-2 Treatment?
Surgery +
Bevacizumab - shrinks vestibular swannomas
Tuberous sclerosis - which gene more common in family inheritance?
De novo/single person affected?
tuberous sclerosis - more common is family or denovo?
Family - TSC1 - Hamartin
Single - TSC2 - Tuberin
De-Novo accounts for majority of TS
Tuberous sclerosis commonly have what complications?
CNS - seizures/ intellectual disability/Tumor- subependymal glial nodules or tubers!
2nd common - renal angiomyolipomata
LAM in Tuberous sclerosis?
Bad prognosis
In Tuberous Sclerosis
- Sirolimus helps in what?
- Everolimus helps in what?
- Rapamycin helps in what?
Sirolimus = reduce Renal (angiomyolipomata) and Lungs lesion (LAM)
Everolimus - reduce Ependymal astrocytomas size and reduce seizures
Rapamycin - improve the Rupa awak ( your face - facial angiofibromas)
premutations mean?
Repeat size is unstable but not having expression (phenotype) of disease
Commonest form of inherited intellectual disability?
Key features of this syndrome?
Fragile X
Key features
- Large ears, long face, large testis
- Intellectual disability
- Behavioural problems
- Mitral valve prolapse!
Dystrophin gene found in what organ?
Muscle
Brain
Heart
Classical features of DMD syndrome?
Proximal muscle weakness = Gower sign
Calf pseudo-hypertrophy ( fat replaces muscle)
Waddling sign
What is strongly found in Down syndrome?
Alzheimers - 1st
Congenital heart disease - 2nd
-VSD! ( ASD = primum ostium)
Hypothyroidism - 3rd
Fragile X gene mutation?
Huntington gene mutation?
Fredreich Ataxia gene mutation?
Fragile X - CGG on FMR1
Huntington - CAG on Exon 1 on Huntington gene
Fredreich Ataxia - GAA on Intron 1
Tumor suppressor gene function?
How it causes problem?
Eg. of tumor suppressor gene?
Cell cycle check points - detect damage and repair
Loss of function - 2 HITS - both alleles have loss of function
Everything else - inherited, familial cancer
Oncogene function?
How it causes problem?
Eg. of oncogene?
Regulate cell growth
Gain of function - gene mutated/over-expressed
RET gene - the only oncogene
Most common gene involved with SOMATIC mutation?
TP53
Brazilian population commonly has what as part of Li Fraumeni syndrome?
Adrenal carcinoma at young age
Li fraumeni - TP53 MISSENSE mutation
Cowden syndrome mutation?
Associated cancers?
Key features?
PTEN
Breast and Follicular thyroid cancer
Large head circumference
Lhermitte-duclos ( mature neuron benign tumors - ganglio-cytoma)
tricho-Lemminomas ( slow growing papules on skin)
How to differentiate FAP ( APC gene) from MutYH polyposis?
MutYH doesn’t have Desmoid tumors
Less polyps ~ 1000
Autosomal recessive!
MutYH protein does what?
repairs oxidative DNA damage - need 2 hit to form disease
Peutz-jegher syndrome mutation?
Clinical features?
STK11 ( Peutz like to sing at karaoke!)
Benign hamartomatous polyposis - becomes intussusception or volvulus = GI cancer
Lip pigmented macules
Lynch syndrome diagnostic criteria?
3-2-1 Hate FAP rule!
3 - family members affected - histologically confirmed
2- successive generation
1 - 1 is diagnosed < 50 yrs old
FAP excluded!
What gene mutation implicated in paraganglioma and phaechromocytoma?
SDHB gene - makes succinate dehydrogenase enzyme to convert energy from food into one that body can use
