GENETICS Flashcards by Jananee Myooran

Features of autosomal recessive inheritance?

Not in every generation
if sibling has it: 2/3 chance of being a carrier, 1/4 not affected

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Name some autosomal recessive diseases?

CF
Alpha 1 antitrypsin
Hemoglobinopathies: SCD, thalaessemia
Haemachromatosis
FMF
Friedrich’s ataxia
SMA
SCD
Kartagener
Homocystinuria

Inborn errors of metabolism
- Tay Sachs
- Wilson

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Features of Autosomal Dominant diseases?

In every generation
50% chance of getting it if you’re a first degree relative; every degree away is 50% of that risk
All affected children have an affected parent

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Name some autosomal dominant diseases?

PCKD
FH
Huntington
Myotonic dystrophy
Tuberous sclerosis
vWF
Malignant Hyperthermia
MND
Di George
Adrenoleukodystrophy

Cancer syndromes: BRCA, MEN, VHL, HNPCC
Genetic syndromes: Noon, Williams
Skeletal syndromes: Marfan, Achondroplasia, Ehlers Danlos
Cardiac: CM, Brugada,

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Name some diseases caused by mosaicism?

Turner
NF1
Tuberous Sclerosis
DMD: gonadal
Achondroplasia: gonadal

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What causes chimeric diseases?

SCT

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Features of X linked recessive diseases?

Males affected more
If father affected: daughters carriers
If mother affected: 50% chance daughters are carriers/ 50% chance sons affected

NO MALE TO MALE TRANSMISSION

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Name some X linked recessive conditions?

Muscular dystrophy: Duchenne, Becker
Hemophilia
CGD
G6PD
Fragile X
Fabry’s

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Examples of X linked dominant conditions?

Alport
Rett

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Examples of diseases with imprinting?

Prader Willi
Angolan

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How can an imprinted disease cause disease?

Loss of imprinting
UPD
Mutation in expressed gene

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Features of mitochondrial diseases?

Passed on from mother ONLY
Affects female and male children

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Homoplasmy vs heteroplasmy; explain?

Mitchondrial disease affects ALL DNA: homoplasmy
Some DNA: heteroplasmy

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What testing can be used for chromosomal variations? Adv and disadv for each?

All can do CNVs

Karyotype: not very small nucleotide variations
FISH: more accurate
Microarray/CGH: most accurate, can do microscopic deletions/duplications; NO TRANSLOCATIONS

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What testing can be used for nucleotide variations? Disadvantage?

Sanger: Gold standard
Next gen sequencing

DISADV: no trinucleotide expansions

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What testing can be used for trinucleotide expansions?

Triplet PCR
Southern Blot

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What testing can be used for imprinting disorders?

Multiplex ligation dependent probe amplication: BEST
Methylation specific MLPA

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What to do with VUS?

Doesn’t confirm dx, don’t use to make clinical decisions, don’t test unaffected relatives, don’t let affect family planning

Suspicious: further studies

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What is lyonisation? What does it result in?

X inactivation (random)

Result
- X linked recessive diseases: females have milder/later phenotype

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Features of XLD disease?

If father has affected X
- Sons unaffected
- All daughters get it

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Features of XLR disease?

Transmitted through carrier females
- Males affected mostly (mother has to give X to all sons)
- Female carriers usually unaffected but CAN BE AFFECTED
- Affected males cannot transmit to sons

If mother is the carrier
- Daughters: 50% chance carrier
- Sons: 50% chance affected
If father has condition
- Daughters will be carriers (has to pass X to daughters)
- Cannot pass onto sons

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Features of mitochondrial disorder?

Have their own extrachromosomal DNA
Inherited through maternal lineage
- Passed onto ALL children
- MALES AND FEMALES affected
- Variable expressivity common
  ○ Children get different mutant load amounts
  - Males cannot transmit disorder

Fragile X features?

Mode of inheritance?

Parkisonism
Cognitive impairment
Tremor
Mood disturbance
Ataxia

X linked dom
- CCG triplet repeat

Examples of imprinting disorders?

Prader Willi

Features of Prader Willi?

Obesity Short DD Hypogonatrophic hypogonadism

Tay Sachs features and transmission mode?

Young death Lipids not broken down --> accumulate in brain Autosomal recessive

Tuberous sclerosis transmission mode and features

Autosomal dominant Growths on scalp/ fingers/ gums/ brain/ lungs/ kidney

Noonan Syndrome features and transmission mode?

Wide set nipples Ptosis Webbed neck wide spaced and down slanting palpebral fissures low set ears Short and wifee nose Delayed cognition CHD: PS Neoplasms Autosomal dominant: PTPN11

Features of NF 1 and 2? Mode of transmission?

NF 1 - Skin: cafe au lait, irish hamartomas, freckling - Optic pathway glioma - Pheochromocytoma/ renal vascular stenosis - Breast cancer - Peripheral n tumour - Osseus lesion - Family history NF2 - Bilateral vestibular schwannomas Autosomal dominant

Marfans features?

Ectopia lentis FBN-1 mutation Aortic aneurysm Wrist and thumb sign

Differentials for Marfan's?

Loeys Dietz: Arterial aneurysm, left palate, skeletal abnormalities, NO ECTOPIA LENTIS Ehlers Danlos:

Most common mutation defect causing dystropinopathies?

Exon deletion

Difference between Duchenne and Becker?

Duchenne: absent Becker: reduced

Symptoms of Duchenne + Becker

Myopathy proximal > distal calf hypertrophy DCM/ HOCM CK elevated

Friedriche's Ataxia features?

Cerebellar Motor weakness Sensory loss to propriception/ vibration Hearing loss Diabetes PRESERVED COGNITION

Spinocerebellar ataxia features?

Cerebellar - progressive ataxia - coordination -dysarthria - cognition dysfunction - sleep - younger onset

Spinocerebellar ataxia mode of transmission?

Autosomal dominant triplet repeat

Di George Syndrome features?

Cardiac abnormality Abnormal facies Thymus aplasia Cleft palate Hypocalcemia Chromosome 22

Klinefelter genetic abnormality?

Extra X chromosome in a male

How to diagnose Klinefelter's genetic abnormality?

47XXY --> karyotype/ chromosomal microarray 48XXXY

Features of Klinefelter?

Physical: small testes, gynaecomastia, infertility, low libido, genetic abnormalities Learning delay Metabolic syndrome Hypothyroidism Osteoporosis

Turner's syndrome genetic abnormality?

45 X, O

Turner syndrome features?

Short stature Cardiac: aortic coarctation/ bicuspid valve Amenorrhea Hypothyroidism Primary ovarian failure

Down's syndrome genetic abnormality?

21 balanced translocation

How to diagnose Down's genetic abnormality?

FISH NOT CMA

Most common cardiac defect in Down's?

Endocardial cushions defect

Haemochromotosis genes and mode of inheritance

Autosomal recessive C282Y H63D

Diagnosis of haemachromotosis? WHat's the earliest sign?

Transferrin: earliest sign High ferritin Low hepcidin MRI: deposits

Chromosome testing looks at cells in which phase?

Metaphase

Effects of protein truncating mutation?

Hapolinsufficiency: 1/2 dose of protein

Effects of mis sense mutation?

Gain of function OR Abnormal protein

Cause of GOF mutations?

Switching back on of a gene which should be switched off after early life Extra gene copies Chromosome translocations -> enhanced gene expression

LOF mutations: what do these genes usually do?

Repairs damaged DNA Regulates cell division Promotes apoptosis of damaged cells

IHC testing: - meaning of presence/absence?

Presence: normal Absence: possibility of gremlin pathogenic variant