Genetics Repeat Expansion Disoders

Question 1

What 5 disorders/traits that are not inherited in a simple mendelian fashion are ??

Answer 1

chromosomal disorders
anticipation and repeat expansion
mitchondrial inheritance
epigenetics (genomic imprintint)
mutlifactorial/polygenic inheritance

Question 2

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.

Answer 2

Myotonic dystrophy

Question 3

Name that disease:

Frequency: 1/20,000; due to repeat expansion in coding region of Huntington protein. Gain of function mutation.

Answer 3

Huntington

Question 4

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.

Answer 4

Fragile X Mental Retardation

Question 5

Expansion to (blank) is a rare event. However, after it has occurred the alleles do not revert and are not rare in the family.

Answer 5

premutation

Question 6

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.

Answer 6

Mytonic Dystrophy

Question 7

In myotonic dystrophy, the disease gets worse by (blank), and the congenital form is seen only in infants of (blank) mothers.

Answer 7

successive generations

affected

Question 8

(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

Answer 8

anticipation

Question 9

In myotonic dystrophy, what is the repeated nucleotides?
HOw many repeats are considered premutation?
Full mutation?
When does the expansion occur?

Answer 9

CTG
50-100
100-2000
During gametogenesis in females (congenital form only occurs in infants from affected mothers)

Question 10

What type of method is used to analyze myotonic dystrophy gene?

Answer 10

southern blot

Question 11

What are cataracts and abnormal electromyogram related to?

Answer 11

mytonic dystrophy

Question 12

mytonic dystrophy is (blank) and anticipatory

Answer 12

dynamic

Question 13

Triplet repeats in certain regions of the DNA are (blank).

Answer 13

unstable

Question 14

If the repeat expands just beyond the normal range, the repeat becomes (blank) and expands in subsequent generations (premutations).

Answer 14

unstable

Question 15

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.

Answer 15

Huntington Disease

Question 16

In hunington disease the full mutation has (blank) percent penetrance, if inherit allele will develop disease.

Answer 16

100

Question 17

In hunington disease
Unaffected individuals: 6-30 copies;
Premutation carriers: (blank) copies;
Affected individuals: (blank) copies.

Answer 17

30-39

36 -180

Question 18

In hunignton, the greater expansion occurs when transmitting parent is (blank).

Answer 18

male

Question 19

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

Answer 19

hunington disease

Question 20

What is the repeated nucleotide sequence of hunington?

Answer 20

CAG

Question 21

What is the most common form of inherited mental retardation?

Answer 21

Fragile X syndrome

Question 22

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.

Answer 22

Fragile X syndrome

Question 23

What is the most common genetic cause of MR?
Most common cause of MR?
Most common inherited cause of M?

Answer 23

Down Syndrome
FAS
Fragile X

Question 23

What is the most common genetic cause of MR?
Most common cause of MR?
Most common inherited cause of M?

Answer 23

Down Syndrome
FAS
Fragile X

Question 24

(blank) refers to the tendency for the mutated X chromosome to undergo a characteristic break in cultured cells.

Answer 24

Fragile X

Question 24

(blank) refers to the tendency for the mutated X chromosome to undergo a characteristic break in cultured cells.

Answer 24

Fragile X

Question 25

Can fragile x be detected in normal karyotyping?

How bout a mutation testing for repeat expansion?

Answer 25

no

yes

Question 25

Can fragile x be detected in normal karyotyping?
How bout a DNA test for repeat expansion?
Prenatal testing?

Answer 25

no
yes
yes

Question 26

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.

Answer 26

Fragile X

Question 27

The full mutation of Fragile X has what kind of penetrance?

Answer 27

100% in males and 50% in females

Question 28

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

Answer 28

FXTAS

Question 29

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

Answer 29

FXTAS and POI

fragile X syndrome

Question 30

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.

Answer 30

Fragile X syndrome

Question 31

All mothers of individuals with an FMR1 full mutation (expansion >200 CGG trinucleotide repeats and abnormal methylation) are (blank) of an FMR1 gene mutation.

Answer 31

carriers

Question 32

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).

Answer 32

FXTAS and POI

fragile X syndrome

Question 33

Males with FXTAS will transmit their FMR1 premutation expansion to whom?

Answer 33

no sons, all daughters (premutation carriers)

Question 34

(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

Answer 34

Carrier testing