Genetics 2-3 Flashcards
What is a polymorphism?
A mutation present in more than 1% of the population.
What are the features of a monogenic genetic disorder?
- Clear pattern of inheritance
- No environmental influence
- Rare
What are the features of a complex genetic disorder?
- Common
- Environmental and genetic influences
- No clear pattern of inheritance
What is a missense mutation?
Single changed nucleotide resulting in a different amino acid being formed and therefore a malfunctioning protein. Known as a point mutation.
What is a nonsense mutation?
Single changed nucleotide resulting in a shorter protein due to a stop codon being coded for. Known as a point mutation.
What are insertion and deletion mutations examples of?
Frameshift mutations
What is incomplete penetrance?
Symptoms are not always present in an individual with a disease-causing mutation.
What is variable expressivity?
The severity of a disease between individuals with the same disease-causing mutation may vary.
What is meant by phenocopy?
Having the same disease but different underlying cause.
What are dominant conditions associated with?
Presence of a toxic protein so require switching off of that mutant gene.
What are recessive conditions associated with?
Absence of a functional protein so restoring the function of this protein is often needed.
What is genetic imprinting?
Genes are expressed differently according to whether they are inherited from the mother or the father.
What is uniparental isodisomy?
When the zygote has all the genetic information from only one parent.
What does maternal uniparental isodisomy result in?
Ovarian teratoma
What does paternal uniparental isodisomy result in?
Hydatidiform mole
What is the mechanism underlying genetic imprinting?
DNA methylation
What is DNA methylation?
The addition of a methyl group to the 5th position on the pyrimidine rings of cytosine.
What is Prader Willi syndrome?
The paternal deletion of a part of chromosome 15, resulting in obesity, short stature, infertility, delayed puberty, mental impairment and behavioural problems.
What is Angelman syndrome?
The maternal deletion of a part of chromosome 15, resulting in development delay, speech impairments, “happy demeanour” , movement disorder (gait ataxia), microcephaly and seizures.
How is mitochondrial DNA passed on?
Via the ovum. The mitochondria in the sperm is lost after fertilisation - only the DNA is transferred to the ovum.
How big is the mitochondrial genome?
16.6kB and 37 genes
What is heteroplasmy?
A mixture of normal and mutant mitochondria present in the same cell. The severity of a disease is dependent on the ratio of affected and unaffected mitochondria.
How many mitochondria are affected to cause no disease?
Up to 3
How many mitochondria are affected to cause a mild disease?
5
How many mitochondria are affected to cause a severe disease?
9
What enzyme is involved in methylation of cytosine?
DNA methyltransferase (DNMT)
What affects methylation patterns?
Environment, age and the type of tissue.
What are two examples of mitochondrial disorders?
LHON - Leber’s heriditary optic neuropathy
MELAS - mitochondrial myopathy, encephalophathy, lactic acidosis and stroke
What are the symptoms of LHON?
- Onset between 20s and 30s
- More common in males
- Bilateral and painless loss of vision leading to blindness
How is LHON diagnosed?
mtDNA analysis or ophthalmological findings.
What is the mutation associated with LHON?
90% are associated with NADH dehydrogenase or cytochrome B mutations.
What are the symptoms of MELAS?
- Vomiting and diarrhoea
- Muscle weakness
- Seizures
What is affected in MELAS?
Muscle and brain most severely due to high metabolic demands (therefore lots of affected mitochondria). Due to phenylalanine being produced instead of leucine.
What is chronic myeloid leukaemia caused by?
Chromosomal translocation/fusion of chromosomes 9 and 22 resulting in the Philadelphia chromosome.
What happens in CML?
Translocation results in production of MCR-ABL1 tyrosine kinase being produced, resulting in overproduction of mature blood cells (granulocytes).
How is CML treated?
BCR-ABL1 tyrosine kinase inhibitors
What is acute promyelocytic leukaemia caused by?
An accumulation of immature granulocytes (promyelocytes)
What genetic change caused promyelocytic leukaemia?
A translocation of the RAR-a gene on Chr17 to PML gene on Chr15, forming PML-RAR-a protein which binds strongly to DNA and blocks transcription.
