Clinical DNA diagnosis Flashcards
silent mutations
nonsense mutations
- point mutation causing a premature stop codon
- the most liikely form of single base substitution mutations
missense
- 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
deletions
- variation
- large deletion results in
- 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
frameshift mutations
- causes (3)
- results in
- can result from insertions, deletions, splicing errors
- often results in a premature stop codon
promoter mutations
-molecular effect and result
- affect the binding of RNA pol to the promoter
- can result in reduced production of mRNA and decreased proteins
tandem repeat expansion
- expansion of tandem repeat sequences (huntingtons, fragile X, myotonic dystrophy)
- can lead to more severe disease as it expands
loss of functions mutations
- 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
gain of function mutations
- AD
- requires a very specific change in the sequence
haploinsufficiency
- definition
- other name
- missing both
- 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
familial hypercholoesterolemis
- type of mutation
- phenotype of the two possible genotypes
- 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
dominant negative
- loss of function
- the mutant product from one allele effects the protein from the normal allele
gain of function
-example and mechanism
- due to a very specific change
- AD
- achondroplasia: receptor is stuck on which prevents chondrocyte formation and short bones
DNA sources
- blood
- buccal swab
- amniotic fluid
genetic differential diagnosis
- chromosomal abnormality
- common microdeletion/duplication
- mehylation disorder
- small duplications/deletions
- single gene disorder
karyotype analysis
-what does it detect
- deletions
- deuplications
- translocations
FISH
- detects known duplication and deletion syndromes
- can detect subtelomeric deletions and duplications
methylation specific RT-PCR
-using bisulfate, cytosine is tunrned into uracil if it is unmethylates
allele specific nucleotide testin
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
multiple ligtion dependent probe amplification
- multiple exons are amplified and then ran out on a gel to determine the preseence of a region
- can show deletions/insertions
utility of population screening
- 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
