Download Uses of Genomic Information in the Diagnosis of Disease

Uses of Genomic Information
in the Diagnosis of Disease
What is Genomics?
 Genetics is the study of inheritance or the
way traits are passed down from one
generation to another
 Genes have the information to make proteins
which direct cell activities and functions and
influence traits such as hair and eye color
 Approximately 30,000 genes in the human DNA
 Genomics is a newer term describing the
study of all of a person’s genes and the
interactions of those genes with each other
and with the environment
Importance of Genomics
 Genomics have a role in 9 of the 10 leading
causes of death in the US
 http://www.cdc.gov/nchs/fastats/deaths.htm
 All humans have 99.9% identical genetic
makeup
 The remaining 0.1% difference may provide
useful information about diseases
 The goal of genetics is to show why some
people get sick from certain infections and
environmental changes while others do not.
Human Genome Project
(HGP)
 A 13 year project where all of the genes in
the human DNA were discovered
 Determined the sequences of approximately 3
billion chemical base pairs that make up the
human DNA
 Completed in 2003 by the U.S. Department of
Energy and the National Institutes of Health
with help from many other countries including
Japan, Germany and France
What are genetic disorders?
 A disease caused in whole or in part by
a variation or mutation of a gene
 Researchers are discovering that nearly
all diseases have a genetic component
What are genetic disorders?
 Some are caused by a mutation in the gene
or group of genes in a person’s cells
 These may be random or from environmental
exposure such as cigarette smoke
Others are hereditary
the mutated gene is passed down through the
family
Most are multifactorial inheritance disorders
-caused by a combination of small variations in
genes, often connected with environmental factors
Three Categories of Genetic
Disorders
 1) Single Gene Disorders
 Caused by a mutation in a single gene. The
mutation may be present on one or both
chromosomes
 Such as Sickle cell disease, cystic fibrosis
and Tay-Sachs
2) Chromosome Disorders
-caused by an excess or deficiency of genes
on the chromosomes or structural changes
within chromosomes
-Down syndrome
Three Categories of Genetic
Disorders
3) Multifactorial Inheritance Disorders
-caused by a combination of small
variations of genes
-heart disease, most cancers, and
behavioral disorders such as
alcoholism, obesity, mental illness,
and Alzheimer’s disease are examples
Genetic Testing
 Today more than 900 genetic tests are
available.
 There are also suseptability tests which
can determine an estimated risk for
developing the disease
 List of common tests available:
http://www.ornl.gov/sci/techresources/Huma
n_Genome/medicine/genetest.shtml
 Database for the entire human genome
 www.genome.gov
Genetic Testing: How it Works
 Scientists scan a patient’s DNA for mutated
sequences
 The DNA sample can come from any tissue
including blood
 For some tests, probes, short pieces of DNA,
are designed with sequences complimentary
to the mutated sequence.
 The probe will seek its compliment among the
base pairs and will bind to it and flag the mutation
Other tests compare the bases in a patient’s gene to
that of a normal gene
Genetic Tests: Types Available
 Carrier Screening- Identifies unaffected individuals who carry one
copy of the gene that needs two to express the
disease
 Preimplantation genetic diagnosis
embryo from in vitro fertilization is tested
before implanted in the uterus
• Prenatal Diagnostic Testing
 Newborn screening
Prenatal diagnostic testing:
What tests show
 Neural tube defects
 Birth defects of the brain or spinal cord
 Chromosomal Abnormalities
Indicated by abnormal amounts of
substances in the mother’s blood such as
alfa-feto protein and estriol
Most fetuses with these abnormalities die
before birth
Prenatal diagnostic testing:
Types of tests
 Ultrasonography
 Performed before other tests to detect obvious
structural defects in the fetus
 Chorionic Villus Sampling
 A doctor removes a small sample of the chorionic
villi, which are small projections that make up part
of the placenta
 Can be done between 10-12 weeks of pregnancy
so the diagnosis is earlier
Prenatal diagnostic testing:
Types of tests
 Amniocentesis
 One of the most common prenatal tests
 A sample of amniotic fluid is removed and
tested for alpha-fetoprotein level
Amniocentesis
Epidemiology
 Human Genome Epidemiology
 http://www.cdc.gov/genomics/hugenet/default.ht
m
The use of the human genome to study vast groups
of people
HGDP
Human Genome Diversity Project
Uses genomics to study different diseases affected
by a person’s genes among ethnic groups
Benefits of Genetic Testing
 Some tests can clarify a diagnosis for a
more concise treatment
 Other tests can prevent families from
having children with devastating
diseases
Disadvantages of Genetic
Testing
 Commercialized gene tests for adult onset
disorders and some cancers
 For presymptomatic people at high risk because of
family medical history
 They only give a probability for developing the
disorder
 People who carry the mutation may never develop
the disorder
Possibility for errors due to contamination or
misidentification
Cost can range from hundreds to thousands of
dollars
Gene Therapy
 Gene therapy is a technique for correcting
faulty genes which cause diseases
 Genes are specific sequences of bases that
encode instructions on how to make proteins
which perform most cellular functions and
make up the majority of the cellular structure
 When defective genes encode proteins unable
to perform properly, genetic disorders can
occur
Methods of Gene Therapy
 A normal gene may be inserted into a
non-specific location within the genome
to replace a faulty gene (most common
method)
 The abnormal gene can be swapped for
a normal gene through Homologous
Recombination.
Homologous Recombination
 The process where two homologous chromosomes exchange a
distal portion of their DNA during prophase 1 of meiosis. The two
homologous chromosomes break and reconnect to the different
end piece. If they break at the same place in the base pair
sequence, the result is an exchange of genes called genetic
recombination. It could be as often as several times per meiosis.

Methods of Gene Therapy
 The abnormal gene can be repaired through
Selective Reverse Mutation, returning the
gene to its normal function
 The regulation of a gene, the degree to which
it is turned on or off can be altered