Personalized Medicine

Question 1

clinical application of NGS

Answer 1

rare undiagnosed diseases

Question 2

pathogen variants __ with phenotype, ___ do not.

Answer 2

pathogenic variants segregate with phenotype, benign variants do not.

Question 3

Is variant polymorphic in “normal” population?

Answer 3

requires accurate DBs with large control populations

Question 4

Is variant de novo in the proband, or inherited from a phenotypically normal parent?

Answer 4

presumes variant is fully penetrant.

Question 5

how do we focus on the variants that are clinically significant?

Answer 5

penetrance assumption
inheritance hypotheses
candidate genes/context
effect/functional/evolutionary predictions.

Question 6

databases: caveat emptor

Answer 6

databases are incomplete
the upstream literature is incomplete.
numerous errors in databases.

Question 7

true or false: loss of function indicates a disease

Answer 7

false

Question 8

false-positive and false-negative variant calles increase with the

Answer 8

size of the sequenced target (gene > exome > genome)

Question 9

Takahashi’s experiment

Answer 9

he took skin cells from adult mice and infected them with a virus to introduce 24 genes. The cells transformed, and looked and behaved like pluripotent embryonic stem cells.

Question 10

What the cells (ES like cells, or pluripotent stem cells) from Takahashi’s experiment were called

Answer 10

induced pluripotent stem cells, or iPS cells.

Question 11

iPS cells are important for

Answer 11

modelling and investigating human diseases, as well as for screening drugs.

Question 12

A prolbem with iPS cells is

Answer 12

consistency - some people have done something remarkable with one cell line, and it turns out nobody else can do it.

Question 13

genes responsible for reprogramming adult cells into iPS cells

Answer 13

oct3/4
sox2
Klf4
c-myc.

Question 14

scientists discovered that iPS cells retain an

Answer 14

epigenetic memory: a pattern of chemical marks on their DNA that reflects their original cell type. Such changes should not affect the cells’ use in therapies.

Question 15

The reslt of implanting retinal pigment epithelium from iPS cells in a patient with macular degeneration was

Answer 15

a halt in the patient’s macular degeneration.

Question 16

most iPS reprogramming teachiques are

Answer 16

inefficient: only a small fraction of cells end up fully reprogrammed. iPS cells vary from one strain to another. That has made it hard to establish controls in experiments.

Question 17

CRISPR-Cas9 gene editing tool, has enabled researchers to

Answer 17

introduce disease associated mutations into a sample of iPS cells and then comparethem with the original, unedited cell lines.

Question 18

because iPS cells resemble embryonic cells, they are not always ideal for

Answer 18

studying late-onset diseases such as dementia.

Question 19

iPS cells have also been used with some success in

Answer 19

drug discovery: they provide a plentiful source of patient derived cells to screen or test experimental drugs.