Gene Scanning

Question 1

In what instances are gene scanning used?

Answer 1

1. testing disorder with extensive allelic heterogeneity

2. families are likely to carry “private mutations” that are unlikely to be on a panel

Question 2

4 possible results of gene scanning:

Answer 2

1. disease causing mutation
2. normal variant
3. variant of undetermined significance
4. negative result (normal sequence)

Question 3

Used to size the entre genome for microdeletions

Answer 3

Microarray

Question 4

What will a CGH array detect?

Answer 4

Deletion or duplication

Question 5

How does obtaining the DNA sequence help in DMD dx?

Answer 5

Since we know the normal coding sequence, we can determine if the bp mutation will be missense, nonsense, etc
(this may not make sense once I leave class)

Question 6

Mom has normal gene and offspring as a mutation. What is the likely cause?

Answer 6

germline mutation or de novo mutation (if there is a 2nd affected child, then you can say germ line mosaicism)

Question 7

Why is it more ideal to test the infected person, rather than the normal offspring?

Answer 7

We know that the affected person has a detectable mutation, once the mutation is determined you can perform a direct genetic test on the proband (otherwise, a negative result testing the proband alone would be fairly inconclusive/could be a false negative)

Question 8

After determining the mutation in an affected person, what test would you perform in related individuals?

Answer 8

Direct test

Question 9

T/f: All mutations can be identified

Answer 9

F

Question 10

In DMD pts they have little or no detectable ____ (a protein)

Answer 10

dystrophin

Question 11

T or F: BMD have normal levels of dystrophin

Answer 11

F: they have lower than normal levels. The closer the levels are to normal, the less sever the phenotype is

Question 12

What types of molecular defects are associated with DMD? (what proportions of pts Dx with DMD have this mutation)

Answer 12

2/3 large deletion in DMD exons

1/3 small insertions/deletions/point mutations

Question 13

What is the mode of inheritence for DMD?

Answer 13

X-linked lethal

Question 14

Will pts with BMD often have a frameshit mutation or a frame neutral deletion?

Answer 14

frame neutral = multiples of 3

Question 15

T or F: there is extensive allelic heterogeneity in BRCA gene mutations

Answer 15

True

Question 16

What is the mode of inheritance for BRCA assc familial breast cancer?

Answer 16

autosomal dominant

Question 17

T or F: There is a limited allelic heterogeneity in BRCA mutations in the ashkenazi Jewish population. (Explain why this is True or False)

Answer 17

T: this corresponds to a “founder effect” (a common ancestor in the pop “brought” in a mutation and that was the one that got passes on)

Question 18

What type of genetic test would be performed if you knew the chromosome/genomic marker that was involved in the phenotype?

Answer 18

linkage

If this is a bad question, feel free to throw it out. I don’t really like it.

Question 19

What kind of genetic test can you perform if you know the gene that is contributing to the disease phenotype that is present?

Answer 19

direct

Question 20

What type of genetic test is performed when there is extensive allelic heterogeneity assc with the disease phenotype?

Answer 20

scanning approach

Question 21

What type of genetic testing is used to screen all or part of a gene to look for any sequence alteration?

Answer 21

scanning approach

Question 22

How is germ line mosaicism “Dx”?

Answer 22

normal genotype in parent(s) with 2 abnormal children with the same mutation

Question 23

When would we perform a genetic screening for a woman’s risk of BRCA assc familial breast cancer?

Answer 23

when she had a greater than 10% risk of having it (determined by algorithm)

Question 24

What parts of the BRCA gene is screened?

Answer 24

promoter, exons, and splice junctions (intron and exon junction)

Question 25

What are some of the limitations to genetic screening?

Answer 25

• mutations outside the scanned region are not detected

- polymorphisms may cause unequal allele amplification (false positive???)

Question 26

Describe how sequence variants are interpreted.

Answer 26

1. evidence based interp (look to data)
2. 3 categories of results: variance is benign, deleterious, or unknown risk
3. Its complicated

Question 27

T or F: If a person gets a negative result from a genetic scanning test they have 0% risk of having a deleterious mutation

Answer 27

F: there are always risks that the test does not pick up