Week 1: Genetics Flashcards
Autosomal Dominant
Genetic disorder transferred from parent to offspring. Vertical pedigree pattern, expressed in heterozygotes, variable expressivity, may be incomplete penetrance.
Eg genetic breast/colon cancer
Autosomal recessive
Musy be homozygous to show phenotype. Horizontal pedigree pattern, expressed in homozygotes, may be consanguinity.
Eg Sickle Cell Anaemia, Cystic Fibrosis
X-linked
RECESSIVE: affects males, show Knight’s move pattern, all daughters carriers
DOMINANT: vertical transmission, all daughters affected
Variable inheritance
individuals in the same family are affected differently by the same gene
Incomplete penetrance
Severity of the same mutation differs from person to person. Common in autosomal dominant conditions
Genetic Anticipation
increased severity and earlier age of onset of mutation through generations. Eg Huntington’s
Mitochondrial inheritance
Genetic material only comes from mother. Disorders tend to affect the muscles, brain and eyes
What does the future of medical genetics involve?
NIPT/NIPD Next Generation Sequencing of whole exomes Personalised Medicine Treating specific genes Tailoring treatments to tumour genotypes
What does gene therapy involve?
Exon skipping in DMD (so you convert DMD to BMD)
Gene editing in CRISPR-CAS9 system
Base editing
How do you do a pre-implantation diagnosis?
remove a couple of cells at 3 days then use PCR/FISH to look at the DNA
What is genetic counselling?
It provides advice or information. The advice should be non-directive
Explain genetic screening
The whole population is offered a genetic test. It can be:
Prenatal (US, maternal blood markers)
Neo-natal (blood spot from heel, Guthrie card, mass spectrometry)
Post Natal (Tay Sachs for Jewish people)
What is heteroplasmy?
Presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual
What are the symptoms of Huntington’s disease
progressive chorea (jerking/writhing movements), dementia, psychiatric symptoms, muscle dystonia, slow or abnormal eye movements
Genetics of Huntington’s
Autosomal dominant w/ genetic anticipation.
Caused by unstable length of chromosome 4 by CAG codon repeats
What are the symptoms of myotonic dystrophy?
progressive muscle weakness, myotonia, cataracts, ptosis
Genetics of myotonic dystrophy
Autosomal dominant w/ genetic anticipation
Unstable length of CTG repeat (causing abnormal DMPK mRNA)
What is cystic fibrosis?
Thicker mucus (recurrent lung infections) CFTR mutation causes defective chloride ion channel which makes mucus thicker. Autosomal recessive
What is neurofibromatosis
Symptoms: cafe au lait macules, neurofibromas, short stature
Autosomal dominant
Complications: hypertension, scoliosis
What are Duchenne Muscular Dystrophy and Becker’s Muscular Dystrophy?
X linked recessive, show knight’s move pattern
Creatinine kinase leaks out of damaged muscle into the blood
Symptoms: Muscle weakness, difficulty standing, unsteady, waddling gait.
DMD = out of frame reading mutation
BMD = in frame reading mutation
What is Fragile X syndrome?
X linked recessive disorder w/ genetic anticipation. Is on the FMR1 gene
Inherited condition characterised by an X chromosome that is abnormally susceptible to damage, especially by folic acid deficiency. Affected individuals tend to have limited intellectual functions.
What is Down’s Syndrome?
trisomy 21
symptoms: learning difficulty, heart defects, hypothyroidism
What is trisomy?
This arises from maternal non-disjunction. The risk increases with maternal age
What are the properties of a cancerous cell?
proliferative signalling; avoidance of apoptosis; bypass replicative senescence; insensitive to anti-growth signalling; needs its own blood supply
