Autosomal Dominant Disorders Flashcards
Define Autosomal Dominant Disorders
Heterozygotes with one copy of altered gene have the condition
What is the pedigree analysis of ADD
In each generation Males = Females Affected people have affected children Male to male transmission Children of affected + unaffected are 1/2 risked
How does the gene cause its effects
Dominant/recessive refer to phenotype
Effect due to gene dosage ie. absence of protein
Most dominant give rise to truncated proteins
What does dominant/recessive pattern depend on
Depends on how cell responds to 1/2 amount of gene product
Dominant = 1/2 amount of structural protein
Recessive = 1/2 normal activity of enzyme
Why do family members that have same altered allele have different signs/symptoms (Variation in expression)
Interaction between other genes from unaffected parent
What is penetrance
Everyone with pathogenic gene alterations shows at least one clinical sign
What is non-penetrant
Has gene but no signs
What is incomplete penetrance
Not 100% of people with disease genotype will show signs
What is the clinical implications of penetrance and variation in expression
Can make person appear they dont have autosomal dominant condition but in actual fact they have the gene
What does new mutations mean
Increase with paternal age due to greater umber of germ cell divisions
What is anticipation
Age of onset decreases
Severity of phenotype increases
in Successive generations
Correlated with repeat length which increases as gene transmitted down
How can kids be affected from unaffected parents
Gonadal mosicism for new mutations
Occurs in mitosis after fertilisation
Up to 50% probability of inheritance
What do you know about Huntington’s Disease
More than 34 repeats of CAG
Protein aggregates in brain cell and cause progressive cell death
Symptoms occur if cells accumulate past critical number
