Single Gene Disorders Flashcards
(50 cards)
What are the classifications of genetic disorders
Single gene disorders
Multi factorial diseases
Chromosome disorders
Mitochondrial disorders
Somatic mutations
What are single gene mutations
Mutations in single genes often causing loss in function
Leads directly to disease
Types of single gene disorders
Dominant - heterozygotes with one copy of the altered genes
Recessive - homozygotes wit two copies of altered gene
X linked recessive - males with one copy of altered gene on X chromosome
Exceptions to Mendels rules in autosomal dominant inheritance
Variance in expression
Penetrance
New mutations
Anticipation
What do majority of mutations in autosomal dominant disorders cause?
Loss of function of the allele
Dominant disorders cause cell to cope with half of the amount of gene product. Examples of this:
50% Structural protein/ receptor clinical effect
50% enzyme - body can cope so no clinical effect
What is Marfans syndrome?
Autosomal dominant condition
Affects skeletal system, heart and eyes
Caused by fibrillins gene on chromosome 15
How can there be diagnosis using DNA
Allows determination of sequence/ copy number variant
Determines whether normal variant or pathogenic (harmful)
What is genotype-phenotype analysis
Sequencing of affected family member to confirm the mutation
What is polymorphism
the presence of two or more variant forms of a specific DNA sequence that can occur among different individuals or populations
How to determine whether a mutation is cause of disease in a family and not just polymorphism
Segregation studies - see whether family members that are clinically affected have same mutation
Genetic testing - see if member with mutation will develop disease
Clinical effects of neurofibromatosis
Skin cafe au last patches
Multiple neurofibroma
Example of a disease with variation of expression
Neurofibromatosis type 1
Exception of Mendels rules of autosomal dominance
Family members have different signs of the same disease
Cant predict severity of the disease
What disease demonstrates age related penetrance
Huntingtons disease
Breast cancer BRCA1
Is NF1 completely penetrant
Yes
If individual has affected gene NF1 always expressed
What is Huntington’s disease
Progressive neurological disorder
Involuntary movements
Dementia
Psychiatric disturbance
What is age dependant penetrance
Delay in onset of a genetic disease
The older they are without signs the less likely they are to develop disease
What is incomplete penetrance
Not everyone who has gene will develop disease e.g. some cancers
What is Achondroplasia
New mutation that causes the disorder in 80% patients
Which disease are new mutations increase with paternal age
Marfan
Achondroplasia
How does a chance of new mutation increase with paternal age
Higher mutation rates in males are likely to be related to greater number of germ cell divisions
What is myotonic dystrophy
Autosomal dominant
Muscle weakness
Impaired muscle contraction after relaxation (myotonia)
Usual age of onset 20s-30s
What is anticipation
- In successive generations age of onset is reduced and/ or severity of the phenotype is increased
- Unstable & expanding trinucleotide repeat mutation
- Severity/ age of onset may correlate with number of repeats
What is an example of anticipation
Myotonic dystrophy
Huntingtons
(Disorders of the nervous system)
