Transcript Risk Assessment and Genetic Predisposition

Genetics: Past, Present, and
Future
Robert M. Fineman, M.D., Ph.D.
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Genetics is that branch of biology
that deals with heredity and
variation.
Genotype: the genetic
constitution of an individual as
applied to a single locus or all the
loci collectively; when applied to
the entire genetic constitution, it
is synonymous with genome.
Alleles: different forms of a gene
at the same locus on homologous
chromosomes.
Phenotype: the appearance or
observable nature of an
individual; the visible effects of
the interaction of the genotype
and the environment.
Medical Genetics: the science or
study of biological variation as it
pertains to health and disease in
humans.
Clinical Genetics or Genetic
Medicine (also known now as
Genomic Medicine): that part of
medical genetics concerned with
health and disease in individuals
and families.
Public Health Genetics: the use
of genetic information and
technology to promote, protect
and, thereby, improve the
public’s health and well-being.
Genetic Screening: the use of
various methods or techniques to
evaluate populations or groups of
individuals independent of a
family history of a disorder, and
without clinical signs or
symptoms.
Genetic Testing: the use of various
methods or assays to determine the
genetic status of an individual
already suspected to be at high risk
for a particular genetic condition
because of a relevant family
history, clinical signs or symptoms,
or a positive screening test result.
Genetic Variation
• There is no such thing as THE human
genome sequence.
• There is about a 3 million bp difference
between any two non-related individuals.
• Common variant sequences (alleles) occur
every 1/1000-1/1500 bp.
• There are an estimated 2-3 common
variants per gene (on average).
DNA Mutations
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Nonsense
Missense
Frameshift
Regulatory
RNA splicing
Expanding trinucleotide repeats
Others
Our Challenge Is One Of Change
• Genetics in the Past
• Human Genome Project/Related Technologies
• New Genetics/Genomics
• Genomic Medicine
• Genomic Medicine and Research
• Genomics and Society
Medical Genetics Timeline
• 1950s: Clinical and mathematical genetics
• 1960s: Cytogenetics, biochemical genetics,
genetic nosology, dysmorphology, NBS
• 1970s: Prenatal screening/dx, genetic
counseling, molecular diagnosis
• 1980s: Early genomics, biotechnology
The Genetics Center Is A
Resource For The Entire
Community
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Preconception: Care/Data/Education
Prenatal: Care/Data/Education
Infant/Childhood: Care/Data/Education
Adolescent/Adult: Care/Data/Education
Usually Involves Other Health and Social
Services Professionals
Medical Genetics Timeline
• 1990s: Computers; Internet; genetic
informatics; genetics of complex diseases;
molecular medicine; ethical, social and
legal issues; commercialization and deacademization; consumerization
Genetics in the Past
• Conditions caused by an extra or
missing chromosome or part of a
chromosome
• Conditions caused by a mutation in a
single gene or in a mitochondria
Genetics in the Past
These conditions:
• are important to the individuals and
families who have them
• are relatively rare, even when added
together
• do not affect most people
• play a small role in health care and
society
Genetics in the Past
These conditions are rare enough
such that genetic services could
be provided by genetic health
care professionals, with
occasional involvement of
primary care professionals and
other specialists.
Genetics in the Past
Regarding research:
• because of their relatively small impact
on the health of our nation, these
conditions were of limited interest
• only very recently did genetics begin to
help answer basic health care questions
Types and Frequencies of Genetic
Diseases
Type
Lifetime Frequency
Chromosomal
Single Gene
Multifactorial
(Emory & Rimoin, 1997)
3.8/1000
20/1000
646/1000
Of the ten leading causes of death in the U.S., nine
are causally related, in part, to genetic/genomic
factors (CDC, 1997).
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Heart Disease (31.0%)
Cancer (23.2%)
Stroke (6.8%)
COPD (4.8%)
Injury (4.2%) (? genetic)
Pneumonia/Influenza (3.9%)
Diabetes (2.8%)
Suicide (1.3%)
Kidney Disease (1.1%)
Chronic Liver Disease (1.1%)
Of the ten leading causes of death worldwide, nine
are causally related, in part, to genetic/genomic
factors (CDC).
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Heart Disease (13.7%)
Stroke (9.5%)
Pneumonia (6.4%)
HIV/AIDS (4.2%)
COPD (4.2%)
Diarrhea (4.1%)
Perinatal (4.0%)
TB (2.8%)
Tracheal/Bronchial/Lung Cancer (2.3%)
Traffic Accidents (2.2%) (? genetic)
Unfortunately, more than 50% of
premature death and disability in
the United States is caused by
things people do to themselves or
to others, e.g., smoking, diet and
exercise, alcohol and drugs,
violence, etc.
The new genetics (or genomics)
comes largely from knowledge
derived from the Human Genome
Project and related technologies.