Clinical DNA diagnosis

Question 1

silent mutations

Question 2

nonsense mutations

Answer 2

• point mutation causing a premature stop codon

- the most liikely form of single base substitution mutations

Question 3

missense

Answer 3

• point mutation which causes a different amino in the polypeptide chain
• conservative mutations are ones which produce similar amino acids
• non-conservative are different types of amino acids based on basicity/acidity or shape

Question 4

deletions

• variation
• large deletion results in

Answer 4

• a portion of the DNA sequence is missing
• varies in size from 1 base to millions of bases
• large deletions can often result in the loss of multiple genes from the same family

Question 5

frameshift mutations

• causes (3)
• results in

Answer 5

• can result from insertions, deletions, splicing errors

- often results in a premature stop codon

Question 6

promoter mutations

-molecular effect and result

Answer 6

• affect the binding of RNA pol to the promoter

- can result in reduced production of mRNA and decreased proteins

Question 7

tandem repeat expansion

Answer 7

• expansion of tandem repeat sequences (huntingtons, fragile X, myotonic dystrophy)
• can lead to more severe disease as it expands

Question 8

loss of functions mutations

Answer 8

• null mutations: classic AR
• haploinsufficiency: when only one copy of a certain gene will not suffice: these are AD/incomplete dominance
• dominant negative is AD

Question 9

gain of function mutations

Answer 9

• AD

- requires a very specific change in the sequence

Question 10

haploinsufficiency

• definition
• other name
• missing both

Answer 10

• only one copy of a gene is insufficient for normal function
• inherited as AD
• also called incomplete dominance
• very severe if both copies are missing

Question 11

familial hypercholoesterolemis

• type of mutation
• phenotype of the two possible genotypes

Answer 11

• loss of function via haploinsufficiency in the LDL receptor
• one mutated allele of LDLR gives somewhat elevated cholesterol with risk for hert disease (AD)
• two mutated alleles creates a much more sever effect with early onset arteriosclerosis with visible deposits of cholesterol in the skin, eyelids, and cornea

Question 12

dominant negative

Answer 12

• loss of function

- the mutant product from one allele effects the protein from the normal allele

Question 13

gain of function

-example and mechanism

Answer 13

• due to a very specific change
• AD
• achondroplasia: receptor is stuck on which prevents chondrocyte formation and short bones

Question 14

DNA sources

Answer 14

• blood
• buccal swab
• amniotic fluid

Question 15

genetic differential diagnosis

Answer 15

• chromosomal abnormality
• common microdeletion/duplication
• mehylation disorder
• small duplications/deletions
• single gene disorder

Question 16

karyotype analysis

-what does it detect

Answer 16

• deletions
• deuplications
• translocations

Question 17

FISH

Answer 17

• detects known duplication and deletion syndromes

- can detect subtelomeric deletions and duplications

Question 18

methylation specific RT-PCR

Answer 18

-using bisulfate, cytosine is tunrned into uracil if it is unmethylates

Question 19

allele specific nucleotide testin

Answer 19

similar in a sens to the micro array that you are introducing single stranded DNA from a patient to single stranded DNA on a slide that has both wild type and the mutation to see where your patients DNA will bind

Question 20

multiple ligtion dependent probe amplification

Answer 20

• multiple exons are amplified and then ran out on a gel to determine the preseence of a region
• can show deletions/insertions

Question 21

utility of population screening

Answer 21

• presymptomatic detection (newborn screens)
• reproductive decision making (knowing the genes you will be passing on)
• benefits should outweigh cost
• optimize sensitivity specificity
• provides screening not testing