Genetics Repeat Expansion Disoders Flashcards
What 5 disorders/traits that are not inherited in a simple mendelian fashion are ??
chromosomal disorders anticipation and repeat expansion mitchondrial inheritance epigenetics (genomic imprintint) mutlifactorial/polygenic inheritance
Name that disease:
Frequency: 1/7000-1/20,000; repeat expansion in protein kinase RNA (after stop codon in 3’ untranslated region of RNA).
Decreases RNA stability.
Myotonic dystrophy
Name that disease:
Frequency: 1/20,000; due to repeat expansion in coding region of Huntington protein. Gain of function mutation.
Huntington
Name that Diseaes:
Frequency: 1/4000 males, 1/8000 females; FMR1 RNA binding protein
(before Met initiation codon in 5’ untranslated region of RNA).
Inhibits transcription due to hypermethylation.
Fragile X Mental Retardation
Expansion to (blank) is a rare event. However, after it has occurred the alleles do not revert and are not rare in the family.
premutation
Name that disease:
Autosomal dominant disorder, affecting 1/8000 individuals.
Skeletal muscle deterioration (starting with face), cardiac and smooth muscle affected as well.
Myotonia (inability to relax muscles), cataracts, and mild mental retardation are also seen.
Mytonic Dystrophy
In myotonic dystrophy, the disease gets worse by (blank), and the congenital form is seen only in infants of (blank) mothers.
successive generations
affected
(blank) is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation
anticipation
In myotonic dystrophy, what is the repeated nucleotides?
HOw many repeats are considered premutation?
Full mutation?
When does the expansion occur?
CTG
50-100
100-2000
During gametogenesis in females (congenital form only occurs in infants from affected mothers)
What type of method is used to analyze myotonic dystrophy gene?
southern blot
What are cataracts and abnormal electromyogram related to?
mytonic dystrophy
mytonic dystrophy is (blank) and anticipatory
dynamic
Triplet repeats in certain regions of the DNA are (blank).
unstable
If the repeat expands just beyond the normal range, the repeat becomes (blank) and expands in subsequent generations (premutations).
unstable
Name this Diseae:
Autosomal dominant, more common in European populations (1/20,000).
Progressive loss of motor control and psychiatric problem including dementia and affective disorder.
Usually presents between ages 30 and 50. Protracted disease, 15 years from diagnosis to death.
Huntington Disease
In hunington disease the full mutation has (blank) percent penetrance, if inherit allele will develop disease.
100
In hunington disease
Unaffected individuals: 6-30 copies;
Premutation carriers: (blank) copies;
Affected individuals: (blank) copies.
30-39
36 -180
In hunignton, the greater expansion occurs when transmitting parent is (blank).
male
Triplet repeat occurs in frame within the coding region and increases number of glutamines.
Leads to toxic aggregates. Binds to
other proteins such as GAPDH and inhibits them.
Greater the number of repeats, the earlier the onset of disease. Greater expansion when transmitting parent is male
hunington disease
What is the repeated nucleotide sequence of hunington?
CAG
What is the most common form of inherited mental retardation?
Fragile X syndrome
Name the disease:
X-linked dominant inheritance; Milder and more
variable expression in females than in males. 1/8000 females and 1/4000 males affected
Overall 80% penetrant in males, 20% penetrant in females.
Fragile X syndrome
What is the most common genetic cause of MR?
Most common cause of MR?
Most common inherited cause of M?
Down Syndrome
FAS
Fragile X
What is the most common genetic cause of MR?
Most common cause of MR?
Most common inherited cause of M?
Down Syndrome
FAS
Fragile X
