clinical DNA dx Flashcards
exam 2
single nucleotide base is changed
point mutations
replace one aa with another
missense mutation
create a premature stop codon
nonsense mutation
same aa produced despite difference in DNA sequence
silent mutation
absence of a portion of DNA sequence
Deletion
a constellation of findings due to a specific deletion the encompasses several genes
microdeletion
not visible karyotype
microdeletion
type of insertion due to repeated regions of DNA, often hole genes
duplications
duplications have to happen right next to each other?
no! may happen in tandem or sited elsewhere in the genome
Charcot-Marie tooth
duplication of PMP22 on chromosome 17
Williams beurene syndrome
chromosome 7 microdeletion
mutations that result in extra DNA sequence
insertion
frameshift mutations can occur by mutiple issues
- deletions -insertions -splicing errors
affect binding of RNA pol to promoter site
promoter mutations
frigle X, mytoninc dystrophy, Hnt’ disease
trinucleotide repeat expansion
Anticipation
expansion of the repeat throughout generations
null mutations
loss of function
PKU
null mutations
haploinsufficiency
Autosomal Dominant
half of normal product is insufficient for normal function
haploinsufficiency
familial hypercholesterolemia
haploinsufficiency
dominant negative
autosomal dominant
mutant protein interferes with function of the protein produced by the normal allele
dominant negative
marfan syndrome
dominant negative
usually due to a very particular change in the gene
gain of function
achondroplasia
gain of function
FGFR3 mutations
receptor is stuck in the “on” position, which prevents chondrocytes proliferations
Challenges of testing (6)
(1) Genetic heterogeneity (2) allelic disorder (3) variable expression (4) non-paternity (5) concerns regarding genetic discrimination (6) mitochondria
DNA Specimens- sources
White blood cells- dna only found in WBC
>3MB test
karyotype
detects known submicroscopic deletion and duplication syndromes
FISH
22q11.2
Di George
angelman/Prader-willi test
bisulfite DNA testing
UBE3A
gene for angelman
sweat test
Gold standard for CF
allele specific oligonucleotide testing for
CF to identify the delta F508 or other common mutations related to this disease
paternity test
short tandem repeat polymorphisms
multiple ligation-dependent probe amplification
deletions in a gene
conservative missense mutations
properties of the amino acid remain the same
non-conservative missense mutations
properties of the AA are different
large deletions often result in the loss of ________
multiple contiguous genes
some crohn’s disease are associated with an
insertion mutation
what is usually the outcome of a frameshift mutation
stop codon introduced leading to a truncated polypeptide
can result in reduced production of mRNA and decreased production of a protein
promoter mutations
causes premature aging and bone marrow disease
dyskeratosis congenita
null mutations are
classic autosomal recessive
null mutations lead to
loss of function
example of genetic heterogeneity
kidney disease caused by multiple genes
different disorders can result from mutations in the same gene
allelic disorder
In Multiple ligation-dependent probe amplification, multiple______ can be amplified at _____ and run out of a gel to determine __________ of region
In MLPA, multiple exons can be amplified at once and run out on a gel to determine presence of region
Silent mutation
deletion mutation
FISH analysis
