Direct Testing Flashcards
What are trinucleotide repeat expansion disorders?
genes containing tandem repeats of 3 basepairs. Unstable expansion of repeat copy number from one generation to the next. Expansion disrupts normal gene function, causing neurologic disease
What is fragile X syndrome?
x-linked. most common form of inherited mental retardation. CGG expansion in 5’ untranslated (noncoding) region of FMR1 gene; expansion accompanied by DNA methylation which shuts down gene expression.
In fragile X syndrome, when does expansion of premutation alleles to full mutation alleles occur?
only during female meiosis
What are the two types of TNR disorders?
TNRs in noncoding regions (such as fragile X) and TNRs with expansion of CAG in coding sequences. (as in huntingdon disease)
What is Friedeich ataxia?
autosomal recessive TNR of GAA
What is myotonic dystrophy and what is the mechanism of its mutation?
expansion in 3’ UTR in DMPK gene, which disrupts normal splicing of other genes because it binds so many splice factors
What is the mechanism for Huntington disease?
expansion of polyglutamine (CAG) tract causes proteins to form toxic aggregates. It is a gain of function allele
What is the mode of inheritance for polyglutamine expansion (CAG) expansion?
all are autosomal dominant because they are gain of function mutations
When do expansion occur in Huntingdon’s disease?
large expansions in male meiosis
What are the general features of TNR disorders?
they become progressively more severe and have earlier onset in successive generations. Caused by successive increase in repeat copy number from generation to generation.
What is myotonic dystrophy?
uncontrollable muscle contractions along with lack of control and muscle wasting.
What is anticipation in reference to TNR disorders?
the disorders increase in severity and have earlier onsets in successive generations.
What does NTM mean?
normal transmitting male.
in pedigrees, it is an unaffected male carrier
If a patient displays somatic mosaicism of a TNR disorder, when did the expansion likely occur?
mitosis
What is direct testing?
determination of genotype for one or more specific mutations. Has high analytic validity for the specific alleles being assayed.
