basics of gentic disorders - key words

Question 1

what is meant by disease anticipation

Answer 1

the onset of the disease gets earlier with each generation (and therefore more severe symptoms too)

> Dyskeratosis congeinita - mutation in telomerase components

> huntingdons
fragile x syndrome

Question 2

what is mutational heterogeneity?

Answer 2

mutations in different areas of the gene (promoter, exon, splice site) all lead to the clinically same outcome

Question 3

what is meant by penetrance

Answer 3

the probability of someone with a particular genotype actually expressing the expected/predicted phenotype
does the trait appear in every individual?

Question 4

what is meant by expressivity

Answer 4

refers to the variability/severity of the phenotype seen

in these mouse ear people - large, small, located at top of head or side of head therefore this is variablr expressivity

'’perfect world’’ would have every genotype = 100%/complete penetrance and narrow expressivity

tuberous schlerosis

Question 5

which best describes mutational heterogeniety
A alleic heterogeniety
B different mutations of the same gene that cause the same disease phenotype
C mutations at different gene loci cause same disease phenotype

Answer 5

OPTION B

option c would descibe locus heterogeneity as seen in chondro-dyplasia

Question 6

can you give an example of variable penetrance?

Answer 6

huntingdons AutDOm degenerative disease due to a GOF mutation in HD gene
resulting in a trinucleotide CAG repeat.

repeats longer than 35 in exon 1 can cause disease but a reduced penetracne at 35-39 CAG s
below 35 is not associated with disease onset

Question 7

can you give an example of mutational heterogeneity

Answer 7

duchenne mucsuclar dystophy and beckers MD there is mutation in dystrophin gene so same loci

but a frameshift mutation is more severe than a SP

Question 8

what is achondroplasia an expamle of?

Answer 8

single gene disorder
GOF autosomal dominant mutation in FGFR3
> shows 100% penetrance and narrow expressivity

Question 9

what is a dominant negative mutations

Answer 9

mutatin where the mutant gene loses function and can prevent normal/wild type genes from functioning correctly
> e.g OI where the trimerisation of collagen is interrupted leading to poor fibrilogenesis

Question 10

can you give an example of variable expressivity

Answer 10

marfan syndrome is AUtDom affecting the gene encoding fibrillin
mild - long and thin fingers
severe - defects in blood vessels including aortic aneurysm

Question 11

what causes non or reduced penetrance?

Answer 11

so what does non penetrance mean? we have a mutation but don’t show phenotype
> epigenetic modifications
> x inactivation
> gene interactions
> location of the mutation/ could be on intron