|Genetic Testing: Reading Your Book of Life|
|Tuesday, 09 February 2010 05:31|
Basically, without variation, the world would be a very bland and colorless place. However, some of this DNA code variation is harmful. Mutations change the way the gene and its product (usually a protein) function and are the cause of hereditary disease. Some mutations have been inherited from a parent, while others have occurred de novo (in the egg or sperm from which an individual was conceived).
Mutations: Genetic "Spelling Errors"
Mutations we are born with are called constitutional, and can be transmitted to our children. Other mutations happen sometime after conception, in the fetus, the infant or the adult, and are thus present only in a limited group of cells or a particular organ. These are called somatic (acquired) mutations. Somatic mutations may also affect our health. In fact, most cancers start with mutations in a single cell, giving it some growth or survival advantage. However, such somatic mutations are not inherited and are only rarely passed down. This said, most somatic mutations will not affect our health directly because those genetic spelling errors will either be repaired by our DNA repair genes, be lethal to the cell in which they occur, or be recognized by the immune system which will destroy the abnormal cell. The deciphering of the genetic code has allowed us to be able to "read" the whole Book of Life, using DNA (molecular) technology. We do not yet understand, however, the relationship of health and disease to many of the variations that lie within. And most of the key information about how the 25,000 chapters in our book of life interact with each other has yet to be deciphered.
Genetic testing: When and How
As more is learned about human/medical genetics, healthcare providers, media, and consumers of genetic services are increasingly seeking information about the availability of genetic testing for specific disorders, and about how genetic testing may be used. Specific gene or chromosome tests are not yet available for all conditions, but the field of genetics is growing rapidly and testing not available this year may be offered next year. Individuals and families who are concerned about a genetic condition will often benefit from a genetic consultation whether or not testing is available for that condition. Many people are seeking information and coping strategies as much as test results.
#1: Genetic Consultation
Who might request a genetics consultation? Anyone who has questions about birth defects or medical conditions in their family such as:
Individuals who are affected by, have a child with, or a family history of: physical birth defects; abnormal growth or mental retardation; a chromosomal abnormality (such as Down or Turner syndrome); an inherited condition such as hemophilia or muscular dystrophy.
Pregnant women who: will be 35 years or older at delivery; have had a positive serum screening result (blood test during pregnancy that reveals the likelihood of certain conditions) or an abnormal ultrasound; are concerned that their medical condition, family history or lifestyle may increase risk to their pregnancy.
Couples who: experience infertility or pregnancy loss; are carriers of autosomal recessive disorders such as sickle cell anemia, cystic fibrosis,Tay Sachs disease, or thalassemia.
#2: Genetic Counseling
Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. Education about inheritance, testing, management, prevention, resources and research. Counseling to promote informed choices and adaptation to the risk or condition.
For the more common genetic disorders, a primary care physician may explain the reasons for and implications of a gene test, and will order it directly. However, most genetic disorders are individually rare, so that diagnosis, testing and clinical management require the help of a specialist, such as a clinical geneticist and/or a genetic counselor.
#3: Genetic Testing/Gene Analysis
Diagnostic testing is used to confirm or rule out a known or suspected genetic disorder in a symptomatic individual. Such may alter medical treatment and may have reproductive or psychosocial implications for other family members as well. Diagnostic testing is appropriate in symptomatic individuals of any age, and is sometimes ordered by a clinical specialist other than a geneticist (e.g. neurologist, endocrinologist). It is important, however, to realize that DNA testing is not always the best way to establish a clinical diagnosis.
Predictive Testing is offered to asymptomatic individuals with a family history of a genetic disorder, and serves to identify those at high risk of genetic disease. This type of testing is medically indicated if early diagnosis will allow interventions that reduce sickness or death. Even in the absence of medical indications, predictive testing can influence life-planning decisions. As predictive testing has psychological ramifications, careful assessment, counseling, and follow-up are important. Many laboratories will not perform predictive testing without proof of informed consent and prior genetic counseling. Predictive testing is strongly discouraged in asymptomatic children at risk for adult-onset disorders unless treatment is available.
Carrier Testing is performed to identify individuals who have a gene mutation for a disorder inherited in an autosomal recessive or X-linked recessive manner. Carriers usually do not themselves have symptoms related to the gene mutation, but may want to know their status in order to make reproductive choices. Carrier testing is offered to those who have family members with a genetic condition, family members of an identified carrier, and individuals in ethnic or racial groups known to have a higher carrier rate for a particular condition.
Finding genetic services
A Working Model: Genetic Testing for Hereditary Predisposition to Cancer
Most cancer predisposition syndromes are inherited as autosomal dominant conditions, which means that each child of an affected individual has a 1 in 2 (50%) risk of inheriting the gene (mutation). The opposite is also true: half of the children of an affected person, on the average, will NOT inherit the gene mutation; these individuals see their cancer risk decrease to that of the general population, and cannot pass down to their children a gene mutation which they do not have.
The first step for the health care provider is to refer the person with a suggestive personal and/or family history of cancer for a genetics consultation. The consultation includes an assessment of genetic risk, followed by genetic education/counseling. The counselor will explain the probability of a hereditary cancer predisposition syndrome, diagnostic or predictive testing which may be available, benefits and limitations of genetic testing, and the implications for managing the patient and his/her family if a gene mutation is identified. The genetics specialist will then coordinate any genetic analysis the patient/family opts for, including practical aspects such as insurance authorization, obtaining blood or tissue samples for testing and forwarding these to the cancer genetics laboratory. When test results are available, the patient and/or family are scheduled for follow-up genetic counseling.
An Example: Genetic Testing for Lynch Syndrome
Putting Life-Saving Information to Use
About the Author: Dawn DeLozier, Ph.D. is Director of Clinical Services at Genetic Medicine Central California and is a UCSF Associate Professor of Pediatrics. Her specialty is Cancer Genetics