Genetics Flashcards
Describe Prader-Willis syndrome
Loss of function of the paternal chromosome
Critical region is deleted OR 2 maternal copies are inherited (uniparental isodomy)
What are the symptoms of Prader-Willis syndrome
Hyperphagia (overeating with loss of regulatory process) Obesity Mental retardation Hypotonia (reduced muscle tension) short Infertile
Describe Angelman syndrome
Loss of function of the maternal chromosome
Imprinting defects OR UB3A mutations
How is Prader-Willis syndrome treated
Diet restriction
Exercise for muscle
Growth hormones
Hormone replacement
What is the karyotype of the mitochondria
36 genes
2-10 copies are circular genomes
Describe MELAS
Mitochondrial myopathy Encephalopathy Lactic Acidosis and Stroke
Progressive neurodegenerative disorder
The muscle and brain have lots of mitochondria so they are heavily affected
What are the symptoms of MELAS
muscle weakness
episodic seizures
stroke-like episodes
vomiting
Describe LHON and what are the symptoms
Leber's hereditary Optic Neuropathy More common in males Bilateral vision (loss of central vision) Optic atrophy Blindness
Describe PKU and its symptoms and treatment
Phenylketonuria Deficiency of phenyladenine hydroxylase Severe retardation Eczema Blonde hair and blue eyes Reduced melanin Remove phenylalanine from the diet
Describe MCAD deficiency and its treatment
Medium chain Acyl coA dehydrogenase deficiency
Common disorder of fatty acid oxidation
Sudden death
Beta oxidation cannot occur so fasting an hypoglycaemia is dangerous
adjust caloric intake and avoid fasting
Give examples of types of mutations
Aneuploidy Translocation chromosome: Macro-deletions Macro-insertions gene: Large insertion Large or deletions
Point mutation
What are the hallmarks of cancer
Dysregulated growth Evasion of apoptosis Limitless replication Sustained angiogenesis Invasion/ metastasis Genome instability and mutation (disordered growth, disordered death, disordered behaviour)
Explain what a polyclonal disease is
Cancer is polyclonal
Many clones of varied genetically distinct cells
Compare driver to passenger mutation
driver - The 1st key mutation
Can cause a normal cell to become a cancer cell
passenger - mutations that don’t contribute to the development of cancer but have occurred during cancer growth
What percentage of breast cancers are caused by germline mutation and of what genes
2.4%
BRCA1 or BRCA2
BRCA2 predisposes to breast cancer in men
Describe breast cancer as mutations
Hit 1 is inherited
hit 2 may not always occur
BRCA genes are TS genes that repair DNA by homologous recombination which cannot happen with mutation
Which defects in cell division or DNA repair influence the risk of familial colorectal cancer
Familial adenomatous polyposis
Lynch syndrome
Describe familial adenomatous polyposis
Thousands of intestinal polyps which contribute risk to colorectal cancer
Caused by the APC gene on chromosome 6
Autosomal dominant
Describe HNPCC
hereditary non polyposis colorectal cancer
Most common inherited form
mutation of MLH1 or MSH2 (DNA repair genes)
Describe oncogenes and tumour suppressors
Proto-oncogenes promote growth and proliferation in cells and those that are in overdrive are oncogenes.
Signalling cascades and mitogenic pathway activation
TS genes regulate cell division, DNA damage, apoptosis and DNA repair
mutations cause loss of function and faulty cell division
Describe chronic myeloid leukaemia
Clonal myeloproliferative disorder => overproduction of mature granulocytes
Middle ages/elderly
3 phases: chronic (benign), accelerated (omnious), blast crisis (acute leukaemic, invariably fatal)
Philadelphia chromosome is found in >90% produces a new tyrosine kinase
What are the indications of testing
Nuchal scan Mid-trimester Previous pregnancies with DS or CF Parents are carriers of chromosome rearrangement or genetic condition FH of genetic condition
Describe the nuchal scan
Looks at the thickness of the fluid at the back of the fetal neck
> 3mm indicates a chromosomal abnormality
Not a diagnostic test
Could be Down’s, Edwards, Patau or cardiac
What is the combined test for Down’s
Combined test =levels of the hormone free beta-hCG +protein PAPP-A
High hCG and Low levels of PAPP-A.
Describe the mid-trimester scan
20 weeks
dates the pregnancy
Diagnose miscarriage or fatal anomalies
What are the reproductive options available
Planning prenatal testing
Facilitating decision making
Seeing patients in clinic following diagnosis in utero
Arrange termination if necessary
Discuss recurrence risks and plans for future pregnancies
Taking into account: previous experiences, family situation, personal beliefs, psychosocial situation, miscarriage risk with genetic risk
What types of scanning are done in pre-natal testing
ultrasound - early scan, nuchal, anomalies in hands, feet, face, lip
MRI at 20 weeks
Describe non-invasive pre-natal testing
Maternal serum screening = testing serum markers in the blood for trisomy 21 or 18 + nuchal measurement
cell-free fetal DNA = analysing DNA fragments in the maternal plasma during pregnancy. baby at 9 weeks. Only 10-20% from the placenta
ultrasound
What are the disadvantages of non-invasive testing
Both not as useful for multiple pregnancies
non-invasive is harder with a greater BMI
Describe Amniocentesis
Invasive
16 weeks onwards
Sample the amniotic fluid which contains fetal cells
1% miscarriage risk, infection, Rh sensitisation
Define heritability
The study of genetic contribution to increased risk of disease
Studies usually use mono and dizygotic twins
What is the copy number variant
Repeated code
Deletions, duplications, insertions that increase polygenic disease risk
Found in obeisty
What are the types of obesity
Monogenic - dominant or recessive single gene disorder
Common - general population
Syndromic - e.g. Prader Willis
What is leptin
Hormone made by adipocytes inwards white adipose tissue which circulates in proportion to the amount of adipose tissue
Inhibits appetite via the hypothalamus
High with high fat
What are the symptoms of monogenic leptin deficiency
hunger obesity no puberty poor growth Low thyroid
Give examples of genes that cause single gene obesity
MC4R = dominant PCSK1 = recessive POMC = recessive MRAP2 = recessive
How is obesity clinically management
Lifelong prevention
Lifestyle measures
Medication
bariatric (weight loss) surgery
How is obesity diagnosed
PCR for diagnosis
Pre-implantation diagnosis for IVF embryos
Mitochondrial transfer (3 parent babies)
What is Sanger sequencing
Amplifying the region of interest with nucleoside terminators
Genetic sequence of the region of interest
What is Next generation sequence
Fragmentation, sequencing and mapping of reads
sequence of the genome/transcriptome
What are the advantages and disadvantages of Sanger sequencing
quick
gives sequence
cannot multiplex
Limited to 2000bp
What are the advantages and disadvantages of next generations sequencing
Massively multiplex
Multiple different libraries
Cost Time Read-depth Data overload Library bias
Describe chorionic villus sampling
Invasive 11-14 weeks 1-2% miscarriage risk Sample of chorionic villi part of developing placenta (same DNA as the foetus) Ealier result than amniocentesis
