Lectures 21-25 Flashcards
AD: What is neurofibromatosis?
An autosomal dominant condition, skin cafe au lait patches, and this may be accompanied by multiple neurofibroma. It shows variation in expression and is completely penetrant.
AD: What is age-dependent penetrance?
What are two examples?
A delay in the onset of a genetic disease
Huntington disease (50% of people with one copy of the altered allele have developed signs by 50)
Breast cancer (80% of women who have inherited BRCA1 allele with a mutation have developed breast cancer by 70)
AD: What is the most common form of dwarfism?
Achondroplasia
new mutations cause a disorder in 80% of patients, it is fully penetrant
AD: Why would the chance of mutation increase with the age of the father?
the older the male gets, the more cell divisions that sperm has had to go through previously, increasing the chances of mutations
What are the effects of anticipation of AD’s?
The phenotype’s age of onset is reduced and the severity is increased in successive generations.
What is a key factor for the severity and age of onset for AD’s?
number of repeats
AD: What causes Huntington disease?
a triplet repeat of CAG - runs of more han 34 CAG repeats in HD gene expand further, causing earlier age of onset in children of men with HD allele (anticipation)
AD: What might happen with gonadal mosaicism?
the production of mutant gametes
AR: What is cystic fibrosis?
How is the gene identified?
an Autosomal Recessive disorder
Look for ‘open reading frames’ and search for CpG islands (gene regulatory regions)
A sweat gland cDNA library would then be screened
AR: What are the assumptions made for the Hardy-Weinberg principle?
remember, this principle can be applied to AD too
random mating
infinitely large population
no preferential selection of genotypes
no new alleles
AR: What are the exceptions to the Hardy-Weinberg principle?
random mating doesn’t always occur!
AR diseases more common in consanguineous matings
What is segregation analysis?
the study of how a disorder is inherited.
AD - compare the affected offspring born to affected parents (penetrance)
AR - segregation analysis is more difficult as some carrier parenTs will have no affected children (TRUNCATION)
What are the three sources of foetal tissue for prenatal diagnoses
placental tissue
amniocentesis
study foetal cells in maternal blood possibly?
How can foetal tissue be studied?
direct muatation analysis (best one)
Genetic linkage analysis, although this requires parental DNA and DNA from a previously affected child
What is a key indication of X-linked inheritance?
No male to male transmission
What are the key symptoms of Duchenne Muscular Dystrophy?
muscle degeneration
cardiac muscle impairment
intellectual impairment
How would Duchenne Muscular Dystrophy be investigated?
serum muscle enzymes (high levels of CREATINE KINASE) muscle biopsy (absence of staining with ANTIBODIES to DYSTROPHIN) molecular genetic analysis (identification of deletions/mutations in DYSTROPHIN)
X - How does Duchenne Muscular Dystrophy occur?
mutations that alter the reading frame result i the absence of the functional dystrophin protein (65%) of cases?
X - What is Becker Muscular Dystrophy?
non frame-shift mutation, which forms a non-functional dystrophin
What is X-inactivation?
males and females need the same doses of X - dosage compensation
The process spreads from an X-inactivation centre on Xq
The XIST gene, expressed from the inqactive X, is important in maintaining the silenced state of the rest of the X chromosome
Why do some females show X-linked recessive traits?
X-inactivation skewwed X-inactivation Turner syndrome (45, X) homozygous for a recessive trait X autosome translocations
How might X-linked dominant diseases be different to AD’s?
XS of affected females
no male to male transmission`
How many genes are in the mitochondrial genome?
37 - most mitochondrial proteins are produced by nuclear genes anyway
How are mitochondria inherited?
maternally, as the sperm mitochondria are actively expelled from the fertilised egg
What happens if a mutation occurs in the mitochondrial genome?
creates a mixed population of mitochondria within the cell called heteroplasmy, as when cells divide, mitochondria are partitioned at random.
AR: how are siblings affected by a single disease?
horizontal transmission
AR: What diseases might show a heterozygous advantage?
sickle cell disease, RBC’s sickle at low O2
heterozygotes are malaria resistant
Heterozygotes for CF have a mutant membrane Cl- channel, which stops typhoid infections from entering
What happens in a autosomal X chromosome translocation?
The X chromosome involved in the translocation survives preferentially to maintain functional disomy of the autosomal genes
