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
(blank) refers to the tendency for the mutated X chromosome to undergo a characteristic break in cultured cells.
Fragile X
(blank) refers to the tendency for the mutated X chromosome to undergo a characteristic break in cultured cells.
Fragile X
Can fragile x be detected in normal karyotyping?
How bout a mutation testing for repeat expansion?
no
yes
Can fragile x be detected in normal karyotyping?
How bout a DNA test for repeat expansion?
Prenatal testing?
no
yes
yes
Name that disease:
Unstable trinucleotide repeat, CGG, normal range 6-55 repeats. Premutation 52-200 repeats; full mutation 200-2000 repeats.
Expansion occurs exclusively through mother.
Probability the premutation will expand to full mutation varies depending on size of the premutation.
100% penetrance in males with full mutation.
50% penetrance in heterozygous females with one full mutation.
Fragile X
The full mutation of Fragile X has what kind of penetrance?
100% in males and 50% in females
Name that disease:
occurs in males (and some females) who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor
FXTAS
Mothers and their female relatives who are premutation carriers are at increased risk for (blank) ; those with a full mutation may have findings of (blank). All are at increased risk of having offspirn with fragile x, FXTAS, and POI
FXTAS and POI
fragile X syndrome
Name that disease:
occurs in individuals with an FMR1 full mutation is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Males may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes after puberty. Behavioral abnormalities, sometimes including autism spectrum disorder, are common.
Fragile X syndrome
All mothers of individuals with an FMR1 full mutation (expansion >200 CGG trinucleotide repeats and abnormal methylation) are (blank) of an FMR1 gene mutation.
carriers
Mothers and their female relatives who are premutation carriers are at increased risk for (blank) ; those with a full mutation may have findings of (blank).
FXTAS and POI
fragile X syndrome
Males with FXTAS will transmit their FMR1 premutation expansion to whom?
no sons, all daughters (premutation carriers)
(blank) for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of an FMR1-related disorder has been confirmed in a family member
Carrier testing
