1. Uses of Genomic Information in the Diagnosis of Disease

2. 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

3. Importance of Genomics
Genomics have a role in 9 of the 10 leading causes of death in the US
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.

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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:
Database for the entire human genome

10. 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

11. 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

12. 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

13. 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 weeks of pregnancy so the diagnosis is earlier

14. 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

15. Amniocentesis

16. Epidemiology Human Genome Epidemiology
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

17. 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

18. 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

19. 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

20. 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.

21. 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. 

22. 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