Genetics Exam #3: Key Terms & Concepts in Personalized Medicine

The human genome project identified a ___________________ (less than, more than) expected number of genes.

less than

- 22,000 (less than many lower organisms)

- a lot of regulatory regions

We as humans are greater than _________% identical

99%

There is more variability ________________ (within, between) ethnic groups than ________________ (within, between) them.

within; between

___________________________________________ can pick up MUCH more than testing single or handful of genes.

Exome/genome sequencing

- Looking for thousands of genes at once

- More than what you need to look at

Exome/genome sequencing has to be very ______________________ to pick up the needle in the haystack.

redundant

- Need to limit holes in the sequence data to not miss a relevant finding

True or False: All labs will interpret the data from exome/genome sequencing the same

False

- They can interpret them differently

- Need clear phenotypic info to understand what might be important

Exome/genome sequencing does NOT detect all genetic abnormalities, such as...

- Pseudogenes

- Triplet repeat disorders

- Methylation abnormalities

- Large genomic rearrangements

Interpretation of results from exome/genome sequencing will _____________________ (change, stay the same) over time

change

- More knowledge about VUSs (benign or pathogenic?)

- More knowledge about genes and associated diseases

- A nondiagnostic result could eventually become a postitive result

Cost of exome/genome sequencing

5-8K

- Cheaper than sequencing a handful of genes individually

True or False: If you know what you're looking for, you should use exome/genome sequencing

False

- Sensitivity of identifying a mutation may not be as good as a targeted multi-gene panel

- Save ES/GS as a last resort!

Identifying a cause of symptoms may provide...

Recurrence risk information and risk assessment for other family members

What is required before doing exome/genome sequencing?

Pre-test genetic couseling

Incidental findings could be identified on exome/genome sequencing. What could the patient opt to include and what can they NOT include?

Option to include:

- Treatable childhood disorders

- Treatable adult-onset disorders

- Untreatable childhood disorders

NOT Included:

- Untreatable adult-onset disorders

How can identifying a cause with exome/genome sequencing affect treatment?

You can treat/manipulate the basis of the disease instead of the symptoms of disease

Why is GWAS done?

Identify variation for more common diseases

- Attempts to quantify risks for individuals/groups

Comparison of risk between two group

Relative risk

- Risk increasing or risk reducing alleles

Exact defined risk

Absolute risk

True or False: Big relative risk might result in small absolute risk

True

MOST of the GWAS ______________ (have, have not) identified significant individual findings.

have not

Limitations of GWAS

- Associations only, not causation

- Replication is absolute requirement

- Need large populations to pick out small effects

- Data needs consistent definition across studies

- Very poor applicability outside those of European acenstry

DTC testing is a ____________________________ screening.

population-based

- Not looking for a targeted clinical finding

- Allows patients to test without a medical provider ordering it

DTC results have more thorough results about _____________________ (medical, non-medical) findings.

non-medical

- Limited clinical utility

True or False: DTC results do not have the same quality control

True

- Could be inaccurate

DTC results can cause...

Undue stress on individuals/families

- Degree of relation

- Degree of ancestry

____________ of disorder does NOT equal _______________ a disorder.

Risk; having

- Inadequate pre- and post-test counseling can misconstrue results' implications

________________________ exist regarding de-identified data, testing minors, and implications on insurance eligibility.

Ethical dilemmas

The use of genomic information in addition to FH, lifestyle, and environmental factors to customize health management

Personalized medicine

Interaction of medications and genes to give correct treatment for the correct person at the correct time

Pharmacogenomics

Some genes determine how well or quickly a medication is...

metabolized

- Affects individual dosing and efficacy in drug

Pharmacogenomics may direct the appropriate drug to be given to a ________________ of affected individuals based on ________________________________.

subset; predicted response

True or False: Pharmaceutical companies are paying for genetic data to identify potential drug targets

True

____________________ is the focus of broad-based utilization from common, complex diseases.

Genomics

Despite capability to sequence the entire genome, __________________________________________ of genomic variants is currently limited but evolving.

interpretation and utility

Clinical ______________________________________ has increased diagnostic yield for complex cases and in some cases lends itself to new therapeutic options.

exome/genome-based testing