Genetics Flashcards
What are examples of autosomal recessive diseases?
Cystic fibrosis Sickle cell disease Haemochromatosis Thalassaemia Tay-Sachs Friedrichs Ataxia - FXN Gene
What are examples of autosomal dominant diseases?
Huntington's Disease Marfan syndrome Retinoblastoma Cerebellar Ataxia - DNMT1 Gene Li-fraumeni syndrome
What are examples of x-linked recessive diseases?
Duchenne - frameshift dystrophin mutation
Becker - inframe insertion dystrophin mutation
Haemophilia
Fabry disease
What are examples of x-linked dominant diseases?
Alports syndrome
Vitamin D resistant rickets
Fragile x syndrome
What is the inheritance pattern for x-linked dominance?
Affected father with unaffected mother
- 100% daughters affected
- 0% sons affected
Affected mother with unaffected mother
- Both sons and daughters have 50% chance of being affected
What is the inheritance pattern for x-linked recessive?
Affected father with unaffected mother
- 100% daughters carriers
- 0% sons not carriers nor affected
Carrier mother with unaffected mother
- 50% daughters carriers
- 50% sons affected
What is a polygenic disease and multifactorial disease?
Polygenic - disease caused by the effects of 2 or more genes
Multifactorial - environmental factors aswell as genetics influence the expression of disease
- T2DM, HTN, Psychiatric disorders
What are recurrence risks and transmission patterns estimates using family histories?
Higher risk if more than 1 family member affected
Higher risk if disease in the proband is more severe
Higher risk if disease in the proband is in the less commonly affected sex
Risk decreases in more remotely related relatives
What are the 6 hallmarks of cancer?
- Sustaining growth signals
- Evading growth suppressors
- Resisting programmed cell death
- Enabling replicative immortality
- Inducing angiogenesis
- Tissue invasion and metastasis
- Abnormal metabolic pathways
- Evasion of the immune system
What are tumour suppressor genes and how are they involved in cancer?
Control cell growth by reducing cell division and inducing cell death, at checkpoints during the cell cycle.
Mutations in both alleles leads to recessive mutation which allows cancers to grow (knudsons two-hit hypothesis)
p53
Rb
BRCA1 and BRCA2
APC
What are oncogenes genes and how are they involved in cancer?
Mutated forms of photo-oncogene that cause the growth and drive of cancer cells - dominant mutation. Increase cell division and decrease cell death
MYC - transcription factor
RAS - G protein
HER2
Cyclin kinases
What is the MAP-Kinase Pathway?
- A growth factor binds to receptor tyrosine kinase on cell membrane which activates RAS
- RAS activates cytoplasmic protein RAF
- RAF activates cytoplasmic protein MEK
- MEK phosphorylates ERK
- ERK moves into nucleus and activates transcription factors which can switch on genes involved in cell cycle/growth/metabolism
- The proteins are eventually switched off - except in mutations = permanently switched on = uncontrolled transcription = cancer
What is the Philadelphia chromosome?
Chromosomal translocation - fusing oncogene with a promotor region so always switched on
Commonly identified in chronic myelogenous leukaemia - CML
What is Li-Fraumeni syndrome?
Autosomal dominant disease of mutations of p53
High risk of cancer
Early onset of sarcomas, breast cancers, brain tumours, adenocortical carcinomas, leukaemia
What are types of mutations that can occur in DNA?
Substitutions Deletions Insertions Copy number change Break points/chromosomal rearrangement
What is the role of telomerase in carcinogenesis?
Telomeres normally shorten with each cell division until eventual cell senescence
Cancers upregulate telomerase to elongate telomeres to keep cells dividing
What is the difference between tumour grading and staging?
Grading - how closely it resembles the tumour resembles tissue of origin - how aggressive it is
Staging - how large it is and how far it has spread - metastatic potential
What occurs in follicular lymphoma?
Increased BCL2 production
Enhanced stabilisation of the mitochondrial membrane to prevent apoptosis - allowing malignant lymphocytes to become immortal
(BCL2 stabilises the membrane by blocking the release of cytochrome C - during apoptosis, BAX disrupts BCL2 to cause cytochrome C to leak from mitochondria to allow for apoptosis)
What are examples of oncogenic viruses and cancers associated with them?
HPV - squamous cell carcinoma of cervix, penis, anus, head, neck
EBV - Burkitt’s lymphoma or nasopharyngeal carcinoma
HepB + C Virus - hepatocellular carcinoma
Human herpes virus - kaposi’s sarcoma
What is a known bacterial carcinogen and 2 tumours associated with this infection?
Heliobacter pylori
Gastric adenocarcinoma + Marginal zone B-cell lymphoma
What cancers are associated with non-ionising and ionising radiation?
Non-ionising radiation
- Squamous cell carcinoma
- Basal cell carcinoma
- Malignant melanoma
Ionising Radiation
- Myeloid leukaemia
- Papillary carcinoma of the thyroid
What is Freidrichs Ataxia?
Autosomal recessive mutation in FXN gene
- important in making frataxin for mitochondria
- GAA trinucleotide repeat expansion
- impaired mitochondria function - low ATP + free radical production
Gait and limb ataxia, pes cavus, scoliosis, cardiomyopathy, HF, diabetes
Progression to wheel-chair - death in 30s
Age: 5-20
What is Cerebellar Ataxia?
Autosomal dominant mutation in DNMT1 gene?
- DNA methyltransferase enzyme involved in DNA methylation
- Neurones in nervous system disrupted
Ataxia, muscle weakness, dementia, hearing loss, narcolepsy, cataracts
Adult onset
What is Beckers and Duchenne muscular dystrophy?
Autosomal recessive mutation in dystrophin
Duchenne - frameshift mutation - no dystrophin produced - 3-5 y/o - death at 15-25
Beckers - inframe mutation - less dystrophin produced - > 7 y/o
Motor delays, gait problems, calf pseudohypertrophy, scoliosis, low IQ, dilated cardiomyopathy, muscle weakness, problems standing up from floor - using hands - gowers sign, learning disabilities
Heart and lung complications
