Quiz 2 Flashcards
Fragile X has what kind of disorder?
CGG in 5’ UTR X-linked
Huntington disease is what kind of disorder?
AD. CAG (poly glutamine disorder)-coding disorder
Freidreich Ataxia has what kind of disorder?
GAA in intron; only AR disorder due to trinucleotide repeat expansion
Myotonic dystrophy is what kind of disorder?
Noncoding in 3’ UTR; means usually parents have it but has not been expressed yet, when doing prenatal testing
How is Achondroplasia inherited?
AD. Most mutations are the same missense change
What perecentage of Achondroplasia is de novo? Whose allele (paternal or maternal) does it arise on and how frequently?
90%.
Arises on paternal allele ALWAYS. NOT on maternal allele
How would you do diagnosis for Achondroplasia?
PCR followed by restriction enzyme digestion
For an X-linked disorder how many PCR bands should a male have? Female?
Only one band for males; they only have one X. Two bands for females
What is penetrance?
ON/OFF individually. Infected grandparent, non-affected parent, affect child. Parent would an expression of non-penetrance
What is variable expressivity?
Dimmer switch - mild to severe
Anticipation?
Decrease of age of onset (younger disease) or increase in severity in generation from generation
Imprinting?
Some parts of the genome are not having expression for both mom and dad’s alleles. Either mom’s allele is expressed or dad’s allele is expressed
Uniparental disomy? What kind of error is it (M1 or M2)
Both chromosomes come from one parent. Error of M2
What is known about mitochondrial DNA?
Inherited almost exclusively from the mother. High mutation rate. Encodes of all respiratory chain complex EXCEPT for complex 2
Why is mutation rate higher in mDNA?
No proofreading. No protective histones. At site of oxidative radical formation
What is the term for a woman who has wild type and mutant mDNA?
Heteroplasmy
What does parent of origin mean?
Parent of origin= imprinting.
Which type of OI is more severe III or IV?
III is more severe. II is lethal. I is mild
What is the overall incidence of OI?
1/10,000
Mutations at which end (carboxy or amino) of Type I collagen are associated with worse phenotype? Where does the helical formation begin?
The carboxy terminal, b/c that’s where formation begins (three strands: two alpha1 and one alpha2)
All four types of OI can have DI, but type I only happens with a certain type of mutation? What is the type of mutation
Missense mutation
What is the most probable amino acid affected in COL1A1 mutation? Why?
Glycine, every third aa is Glycine. It is the only aa small enough to fit in a pocket
Why is Cysteine mutation of COL1A1 tolerated as a mild form but not Aspartate (lethal)?
Cysteine is just like Glycine in terms of being non-polar and neutral. Aspartate is polar and acidic, so it is lethal
What are the two main mechanisms of OI?
Haploinsufficiency and Dominant negative
Do you have DI with haplosufficienty in OI? DI with Dominant negative OI?
No. Yes. Dominant negative has DI expression.
Bottom line is, not enough collagen is not DI. Mutant type of collagen then there is DI
OI has 80% of what kind of mutation? 20% of what typeof mutation?
80% substitutions for glycine in either type 1 collagen chain.
20% cause abnormalities of splicing
Which type of OI is lethal and can be ruled out?
Type II
