Human Genetics: Concepts and Applications (Lewis), 9th Edition

Chapter 20: Genetic Testing and Treatment

Chapter Outline

CHAPTER OVERVIEW

1. Geneticists are trained to diagnose rare diseases from symptoms and family history
2. Genetic testing is becoming a more common diagnostic tool in medical practice

1. Genetic disease differs from other conditions in that recurrence risk is predictable and predictive testing is possible.
2. A genetic counselor provides information to individuals, couples, and families on modes of inheritance, recurrence risks, genetic tests, and treatments.
3. People often seek genetic counseling related to pregnancy or when an inherited disease is present in the family.
4. Healthy adults often have concerns about screening for potential disease associated genotypes.
5. A nondirective approach has traditionally been used by genetic counselors. The current trend is toward shared decision making.
6. There is currently a shortage of qualified genetic counselors.
7. Online and direct-to-consumer genetic testing services may increase anxiety or foster misconceptions.

1. Genetic testing is becoming an increasingly important part of healthcare.
2. Widespread use of genetic testing raises privacy and ethical concerns.
3. Tandem mass spectrometry is used to provide newborn screening for a wide variety of inborn errors of metabolism.
4. Technology is making it possible to improve and expand screening for newborns and others while lowering costs.
5. The American College of Medical Genetics has recommended testing for 29 genetic conditions in newborns.
6. The purpose of screening is to assist with diagnosis and begin individualized treatments early.
7. Direct-to-consumer testing is increasingly available. Without appropriate genetic counseling, such services may be misleading or harmful for consumers.
8. Pharmacogenetic and pharmacogenomic testing can aid in diagnosis and treatment.

1. Many therapies replace gene products to treat the disease phenotype.
2. One example is Gaucher disease, a rare disorder which is being treated with enzyme replacement therapy.

1. Gene therapies replace malfunctioning or absent genes.
2. Germline gene therapy targets gametes or fertilized ova and is heritable.
3. Somatic gene therapy targets various types of somatic tissue as well as cancer cells and is not heritable.
4. Ex vivo gene therapy involves injection of engineered cells into patients.
5. In vivo gene therapy involves injecting the vector directly into the body.
6. Vectors for delivering genes include liposomes and viruses.
7. Viral vectors differ in the type of cell they can enter, and in how large a gene they can carry.
8. Stem cells are being pursued as sites for gene therapy since they have greater potential for division.
9. Genetically altered endothelium implanted in blood vessels secretes needed proteins into the bloodstream.
10. Skin cells can be genetically altered in culture, expanded, then grafted onto animals, where they secrete foreign gene products.
11. Muscle is potentially a good target for gene therapy because it is accessible, near a blood supply, and abundant.
12. The liver is the largest organ and is a good target for gene therapy since it has many functions and can regenerate.
13. Lung disorders can be targeted using disabled cold viruses in aerosols that can deliver genes to lung cells.
14. Nerve cells have proven difficult targets since they typically do not divide. They may be treatable by genetically engineering and transplanting fibroblasts or glial cells.
15. Cancer cells are of great interest as targets of gene therapy.

1. In 1986 PEG-ADA was first used to treat ADA-deficient SCID. Initial results were promising.
2. In 1990, a four-year old girl with ADA-deficient SCID, became the first person treated with gene therapy.
3. The gene therapy used in 1990 involved infusions of T-cells that had been transduced with a gene for ADA. This therapy resulted in partial restoration of immune function in the patient.
4. SCID trials in France have led to patients developing leukemia.

1. In 1999, gene therapy for OTC deficiency led to a tragic death of an eighteen-year old patient.
2. The patient died as the result of an unexpected severe immune reaction to the virus used to deliver the OTC gene. All gene therapy protocols were carefully reviewed.

1. Canavan disease results in demyelination of brain neurons.
2. Restoration of aspartoacylase activity via gene therapy seemed to stop demyelination in a human patient.
3. Gene therapy for Leber's congenital amaurosis has improved sight in dogs and humans.

1. Gene therapy has been advancing slowly.
2. Human genome sequence data have highlighted the complexities involved.
3. Future applications will require advances in vectors to provide long lasting, safe genetic correction.