Deck 32: Advances in Neurogenetics: The Study of Huntington Disease

Question 1

Gene silencing has been effective in mouse models of HD that are heterozygous for the mHTT gene.The results are promising as_______ .

A)the injection into both sides of the mouse brain resulted in reduced mHTT
B)the study demonstrated the ZFN only targeted the mHTT allele and left the normal HTT expression level unchanged
C)the injection into one side of the mouse brain affected both sides of the brain
D)both mHTT and HTT were down regulated

Answer 1

the study demonstrated the ZFN only targeted the mHTT allele and left the normal HTT expression level unchanged

Question 2

Other neurodegenerative diseases also function through aggregation of misfolded proteins.However,the initial protein aggregates are different in each disease.Work on HD may still be vital to treating other diseases as_______
.

A)not all neurodegenerative disease spread
B)the method of disaggregation is similar in all neurodegenerative disease
C)other neurodegenerative diseases use axonal transport to spread to unaffected cells
D)the method of aggregation is the same in all neurodegenerative disease

Answer 2

C

Question 3

Explain how the use of sequencing technologies finally brought the search for the HD gene to a close as reported by the Huntington's Disease Collaborative Research Group.

Answer 3

Sequencing of the contigs that covered the end of Chromosome 4 that had been previously identified as the location of the HD locus revealed an "interesting contig" that contained a CAG repeat sequence.The population of individuals without HD had 17 alleles with CAG repeats varying from 11 to 34 copies.HD individuals had alleles with 42-66 repeats of the CAG trinucleotide.HD was known to be a trinucleotide repeat disease and the research group proposed HTT as the gene responsible for HD and named its gene product huntingtin.

Question 4

Neurogenetics is_______ .

A)the study of genes associated with the formation of neurons
B)the study of the genetic basis for neurodegenerative disease
C)the study of genetics that makes human brains unique
D)the study of the protein basis for neurodegenerative disease

Question 5

Why does the mHTT gene have such wide- ranging effects in the disease state?

Question 6

Researcher Xiao- Jiang Li has used _______to edit the exon of hua mutant HTT allele in mice.Three weeks after the injection of therapeutic into the brain the mice demonstrated a reduction in protein aggregates.

A)lentiviral transfection
B)CRISPR- cas
C)TALENs
D)ZFNs

Question 7

Huntington's observations of the disease that later took his name were published prior to the rediscovery of Gregor Mendel's work on inheritance.Support the argument that Huntington was describing a phenotype with complete dominance.

Question 8

HD heredity seems to increase if a father inherits the mutant allele from his mother.This is most likely caused by_______ .

A)imprinting
B)selection
C)segregation
D)recombination

Question 9

An important study of HD conducted by A.Yamamoto demonstrated that turning off the HTT gene early in the progression of the disease results in the aggregates being degraded and prevention of the disease.Explain how Yamamoto designed his experiment.

Question 10

The second study by Gusella demonstrated four haplotypes for HD based on the restriction enzyme HindIII. Which haplotype demonstrated linkage to the disease phenotype?

A)A
B)B
C)C
D)D

Question 11

The success of Gusella,Wexler,and their colleagues in mapping both the G8 marker and HD gene to chromosome 4 launched a new branch of genetics called_______ .

A)personalized medicine
B)genomics
C)neurogenetics
D)reverse genetics

Question 12

How do Parkinson's causing aggregates enter unaffected cells?

A)exocytosis
B)phagocytosis
C)endocytosis
D)alpha- synuclein aggregates cannot enter unaffected cells

Question 13

HD was the first example of complete dominance in human inheritance.Describe the impact this has on inheriting the disease state.

Question 14

The favored model organism for studying the development of HD is_______ .

A)H.sapiens
B)M.musculus
C)C.elegans
D)D.melanogaster

Question 15

HD is known as a polyQ disease.How does "polyQ" relate to HD?

A)There are many trinucleotide repeats,which are called "Qs" in the disease state.
B)There are many Q nucleotides added to the HTT gene in the disease state.
C)There are many Q amino acids added to the huntingtin protein in the disease state.
D)There are many CAG repeats,which code for glutamic acid residues in the disease state.

Question 16

How does the development of protein aggregates in Huntington's disease bring about dementia in patients?

A)disruption of the neuronal connection to the frontal lobe resulting in brain weight gain of ~30%
B)disruption of the neuronal connection of the entire central nervous system
C)disruption of neuronal connection between the medulla and the caudate region
D)disruption of neuronal connection between the caudate region and the frontal lobe

Question 17

Early mapping of the HD gene was done using _______.

A)northern blotting
B)RFLP mapping
C)SNP mapping
D)WGS

Question 18

Since the discovery of the HTT gene,genetic testing for the number of CAG repeats has been developed.However,there are serious ethical questions raised by the prospect of prenatal testing as well as the testing of minors.Develop an argument for why minors should not be tested for HD unless they demonstrate juvenile HD symptoms.

Question 19

Huntington's disease HD)is the model neurodegenerative disease because_______ .

A)it is monogenic
B)only a few analytical approaches have been used to study it
C)it does not have a defined set of symptoms and disease progression
D)it is not 100% penetrant