The “New Genetics”: What Is It And Why Do We Care?

roachavocadoBiotechnology

Dec 14, 2012 (5 years and 23 days ago)

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GENOMIC MEDICINE

AND

PUBLIC HEALTH








August 16, 2000








Alan E. Guttmacher, M.D.

Senior Clinical Advisor to the Director

National Human Genome Research Institute
National Institutes of Health


What We Will Consider


The “old genetics”


The Human Genome Project


The “new genetics”
-

genomic
medicine


The new genetics and health


The new genetics and society

The “Old Genetics”


About conditions
wholly

caused by:


An extra or missing chromosome
or part of a chromosome


e.g., Down syndrome, Turner
syndrome, cri
-
du
-
chat syndrome


A mutation in a single gene



e.g., cystic fibrosis, Marfan
syndrome, phenylketonuria

The “Old Genetics”


These conditions


Are of great importance to
individuals and families with them


But, even when added together, are
relatively rare


Most people not directly affected


Genetics thus played relatively small
role in health care (and in society)

The “Old Genetics”


These conditions are rare
enough that:



Genetics care could be supplied
primarily by medical geneticists
and genetic counselors, with
occasional involvement of primary
care providers and other
specialists

The “Old Genetics”


In terms of research:



Because of their small impact on
health, these genetic conditions of
relatively limited interest


In past two decades, genetics of
relatively little help in answering
basic questions, but of increasing
help as source of lab tools

>

9 of the CDC’s 10 Leading Causes of
U.S. Deaths Have Genetic

Components


1. Heart disease (31.0% of deaths in ‘98)


2. Cancer (23.2%)


3. Stroke (6.8%)


4. COPD (4.8%)

?
5. Injury (4.2%)


6. Pneumonia/Influenza (3.9%)


7. Diabetes (2.8%)


8. Suicide (1.3%)


9. Kidney disease (1.1%)


10. Chronic liver disease (1.1%)


>

9 of the WHO’s 10 Leading Causes of
Global Deaths Have Genetic

Components


1. Heart disease (13.7% of total in ‘98)


2. Stroke (9.5%)


3. Pneumonia (6.4%)


4. HIV/AIDS (4.2%)


5. COPD (4.2%)


6. Diarrhea (4.1%)


7. Perinatal (4.0%)


8. Tuberculosis (2.8%)


9. Trachea/bronchus/lung cancer (2.3%)

?
10. Traffic accidents (2.2%)


The “New Genetics”
-


Genomics


Comes largely from knowledge
emanating from the Human
Genome Project

The Human Genome Project


An international government project
that is ahead of schedule!


And under budget!!


And from its start has earmarked
funds for consideration of its
ethical, legal, and social implications
(ELSI)
-

the largest funding ever
devoted to bioethics!!!

The Human Genome Project


The human genome consists of
about three billion chemical bases


It would fill 150,000 telephone book
pages with A’s, C’s, G’s and T’s


Disease is often caused by a single
variation in the three billion bases
-

one letter in the 150,000 pages


Our challenge is partly one of scale

Human Genome Project
-

Sequence Progress


Draft =
65.7%


Finished =
21.1%


Total =
86.8%


As of 6/11/00

As of 6/18/00

As of 6/25/00

The Human Genome Project


That is “only” the “race” for the
human genome sequence
-

the
alphabet


Vital tool, but of little impact itself


The real fun, and the real impact
on peoples’ lives, comes from
figuring out how words and
sentences are formed and then
creating new poetry

The Human Genome Project


Which brings us back to the
genomic medicine…

Genomic Medicine


About conditions
partly
:


Caused by mutation(s) in gene(s)


e.g., colon cancer, breast cancer,
atherosclerosis, inflammatory bowel
disease, diabetes, Alzheimer disease,
mood disorders, many others


Prevented

by mutation(s) in gene(s)


e.g., HIV (CCR5), ?atherosclerosis,
?cancers, ?diabetes, many others


Genomic Medicine


These conditions


Are also of great importance to
individuals and families with them


But are quite common


Directly affect virtually everyone


Will make genetics play large role
in health care and in society

Genomic Medicine


So far, most success identifying
genetic contributions to common
disease has been for low frequency,
high penetrance alleles, e.g.:


HNPCC (colon cancer)


BRCA1 and 2 (breast & ovarian Ca)


MODY 1,2,3 (diabetes)


Alpha
-
synuclein (Parkinson disease)

Genomic Medicine


But, on a population level, most
genetic contributions to common
disease are from high frequency,
low penetrance alleles, e.g.:


APC I1307K and colon cancer


ApoE and Alzheimer disease


Factor V Leiden and thrombosis


CCR5 and HIV/AIDS resistance

Genomic Medicine


So, much more to come, in the
next few years, as these
genetic contributions to more
common disease are
identified…

Genomic Medicine


These conditions are common
enough that:



Genetics care will be supplied
primarily by primary care
providers from many health
disciplines, with occasional
involvement of medical geneticists
and genetic counselors and other
medical specialists

Genomic Medicine


These conditions are common
enough that:



Genetics rises to the level of a
focus for public health
professionals

Genomic Medicine


These conditions are common
enough that:



Genetics rises to the level of a
focus for public health
professionals


Might genetics be to public health
in the 21st century what
infectious disease was in the
20th?

Genomic Medicine


In terms of research:



Because of their great impact on
health, these conditions are of
great interest


In next two decades, genetics will
provide not only even better lab
tools, but also answers to many
basic biological questions

Genomic Medicine


Will change health care by...


providing knowledge of individual
genetic predispositions


creating pharmacogenomics


allowing population based
screening for certain Mendelian
disorders

Genomic Medicine


Knowledge of individual genetic
predispositions will allow:


Individualized screening,


Individualized behavior changes


Presymptomatic medical therapies,
e.g., anti
-
colon cancer agents before
colon cancer develops,
antihypertensives before hypertension
develops

Genomic Medicine


Pharmacogenomics will allow:



individualized medication use
based on genetically determined
variation in effects and side effects


use of medications otherwise
rejected because of side effects


new medications for specific
genotypic disease subtypes

Genomic Medicine


Will change health care by...


providing better understanding of
non
-
genetic (environmental)
factors in health and disease


emphasizing health maintenance
rather than disease treatment


allowing genetic engineering

Genomic Medicine


Will change both health care
and research by creating…


a fundamental understanding of
the etiology of many diseases,
even “non
-
genetic” diseases






Genomics


May include characteristics that
most do not see as “diseases”
and many do not see as innate



e.g., height, intelligence,
sexual orientation, alcoholism,
violence, happiness
-
sadness,
confidence
-
anxiety, altruism
-
greed

Genomics


Will also change our lives by…


Allowing everyone to know their
own (and maybe others’) health
and disease predispositions


Allowing everyone to know their
own (and maybe others’)
“characteristics” predispositions


Showing that we are all mutants


Genomics


May also change society through


Social stratification by genetic
status, e.g., in employment or
marriage


Genetic engineering against (and
for) diseases and characteristics


Cloning


Increased opportunity for “private
eugenics”

Genomics


Raises new concerns, such as:


Discrimination against individuals


Discrimination against groups


Genes run in families


Genetic determinism


Will we have false impression of
our futures?


Nature over nurture?



Genomics


And more concerns, such as:


Fairness in access


Confidentiality/privacy of
information


Right not to know and not to act


What is appropriate informed
consent process for genetic testing


Patenting and licensing


How Do Health Professionals Prepare for
Genomic Medicine?


Need to learn to “think genetically”
-

to:


realize when genetic factors play a role


effectively use family hx & genetic tests


be able to explain genetics concepts


deal with “risk” & genetic predisposition


realize personal and societal impact of
genetic information


protect genetic privacy


use genetics to individualize patient care


use genetics to preserve health

The National Coalition for Health Professional
Education in Genetics


(NCHPEG)


Seeks to:


integrate genetics into the knowledge
base of health professionals & students


develop educational tools & information
resources to facilitate health
professional integration of genetics into
practice


strengthen & expand the community
committed to coordinated national
genetics education for health
professionals

The National Coalition for Health Professional
Education in Genetics


(NCHPEG)


Over 100 member organizations
(including the Association of
Schools of Public Health)


Web site at: www.NCHPEG.org

How Does Society Prepare for the
Genomics?


Education to achieve understanding of:


the basics of the science of genetics


the eventual use of genetics in health
care


how to deal with risk and predisposition


the personal impact of genetics
information


the societal impact of genetics

The Future (?2010)
-

Alzheimer
Disease, for example


5 or 6 genetic variations identified that
strongly predispose for Alzheimer
disease; another 10 or 12 with weaker
association


Chip
-
based genetic test gives personal
likelihood of developing the condition


Chip
-
based genetic test identifies the
drug most likely to be effective for given
individual


Chip
-
based genetic test determines
individual likelihood of drug side effects

The Future (?2010)
-

Asthma,
for example


Genetic testing reveals which genetic
subtype of asthma an individual has


Therapy, both environmental
-
protective
and medical, chosen based on this
subtyping


Another genetic test identifies the drug
most likely to be effective for given
individual


Another genetic test determines
individual likelihood of drug side effects