Browse topics
Genetics
16 notes, 50 questions and 141 flashcards.
Tier 1 is core knowledge expected of every trainee. Tier 2 is deeper or less common.
Endocrinology
Genetic and metabolic medicine
- Autosomal dominant and recessive inheritance, penetrance and carrier riskFree samplePedigree features of autosomal dominant and recessive inheritance, penetrance and expressivity, de novo variants, and worked carrier and recurrence risk calculations using Hardy-Weinberg and Bayes.Tier 1, medical sciences concept, 3 questions, 9 flashcards
- Oncogenes, tumour suppressor genes and the two-hit hypothesisFree sampleGain-of-function oncogenes versus loss-of-function tumour suppressors, Knudson's two-hit model with the retinoblastoma arithmetic, how second hits happen, and why this explains hereditary cancer patterns and targeted therapy.Tier 1, medical sciences concept, 3 questions, 8 flashcards
- Defining pathogenicity of genetic variantsThe ACMG/AMP five-tier system for germline variants, the evidence types behind it, the points-based scoring that labs now use, and what a variant of uncertain significance means for the patient and family.Tier 2, medical sciences concept, 3 questions, 8 flashcards
- DNA repair defects, microsatellite instability and synthetic lethalityThe main DNA repair pathways and the syndromes caused by losing them, how mismatch repair loss produces microsatellite instability and checkpoint inhibitor sensitivity, and why PARP inhibitors kill homologous recombination-deficient tumours.Tier 2, medical sciences concept, 3 questions, 8 flashcards
- Epigenetics, genomic imprinting and uniparental disomyDNA methylation and histone marks, parent-of-origin imprinting at 15q11-q13 and 11p15, how uniparental disomy arises, and the clinical tests and drugs that depend on methylation.Tier 2, medical sciences concept, 3 questions, 8 flashcards
- From DNA to protein: replication, transcription and translationHow DNA is copied, transcribed, spliced and translated, how variants at each step change the protein, and which drugs and toxins act on each step.Tier 2, medical sciences concept, 4 questions, 10 flashcards
- Massively parallel sequencing: gene panels, exome and genomeHow short-read massively parallel sequencing works, what read depth and allele fraction mean, and how to choose between a gene panel, exome and genome, including what each one misses and how secondary findings are handled.Tier 2, medical sciences concept, 3 questions, 8 flashcards
- Mitochondrial inheritance and heteroplasmyMaternal inheritance of mtDNA, heteroplasmy, the threshold effect and the bottleneck, the classic syndromes (MELAS, MERRF, LHON, Leigh), drug hazards and Australian mitochondrial donation.Tier 2, medical sciences concept, 3 questions, 10 flashcards
- Multifactorial and polygenic inheritance and polygenic risk scoresThe liability-threshold model, empirical recurrence risks, heritability from twin studies, and what a polygenic risk score can and cannot tell a patient, with worked numbers.Tier 2, medical sciences concept, 3 questions, 9 flashcards
- PCR and Sanger sequencingHow PCR amplifies a target and Sanger sequencing reads it, what each can and can't detect, and where they still appear in practice (familial variant testing, BCR-ABL1 monitoring, repeat expansions).Tier 2, medical sciences concept, 3 questions, 8 flashcards
- Polymorphisms, mutations and their molecular consequencesPolymorphism versus mutation versus variant, germline and somatic change, variant types and their effect on protein, loss and gain of function, and how to read HGVS notation.Tier 2, medical sciences concept, 3 questions, 9 flashcards
- Trinucleotide repeat expansion and anticipationHow unstable repeats expand between generations, the repeat thresholds for Huntington disease, myotonic dystrophy and fragile X, parent-of-origin effects, and why standard sequencing misses them.Tier 2, medical sciences concept, 3 questions, 9 flashcards
- X-linked inheritance and X-inactivationX-linked recessive and dominant pedigrees, carrier risk calculations, and how skewed X-inactivation explains symptomatic female carriers of DMD, haemophilia and Fabry disease.Tier 2, medical sciences concept, 3 questions, 9 flashcards
Haematology
- Sickle cell disease: molecular basis and pathophysiologyThe HbS point mutation, the kinetics of deoxy-HbS polymerisation and the factors that drive it, how haemolysis and vaso-occlusion produce the complications, sickle trait, and how hydroxyurea, transfusion and gene therapy work.Tier 2, medical sciences concept, 3 questions, 9 flashcards
- Thalassaemia: molecular genetics and pathophysiologyGlobin gene organisation, how alpha and beta thalassaemia arise, why chain imbalance causes ineffective erythropoiesis and iron overload, how carriers are identified, and the mechanisms of newer therapies.Tier 2, medical sciences concept, 3 questions, 9 flashcards