Classes Of Dna Tests

The unique feature of DNA in molecular genetics/ genomics is its ability to use this approach to investigate many clinical scenarios (Table 1). The range is extensive, starting with the straightforward DNA diagnostic test confirming that an individual with a clinical problem has a genetic disease. The next level of complexity involves population screening, or DNA predictive testing for late-onset genetic disorders. Many of these DNA tests require

Table 1 Classes of DNA genetic tests

DNA test and description


Diagnostic—A DNA test used to confirm a clinical suspicion that the patient has an established disorder. The DNA test in this circumstance is comparable to a blood count or measurement of a biochemical analyte, although a positive result has implications for family members. Prenatal—DNA test to detect a genetic disorder in the fetus or embryo.

Screening—A DNA test used to look at asymptomatic individuals (or populations) to determine who are carriers or who have a genetic predisposition.'3'4-1 Various types of screening options are available.

Predictive or presymptomatic—A DNA test used to predict the development of a genetic disorder in advance of any signs or symptoms (for convenience' a distinction is not made between predictive and presymptomatic).'5-

A suspected case of hemochromatosis can be confirmed by a liver biopsy' a procedure that has associated morbidity and mortality. An alternative is a DNA test' used to look for the common hemochromatosis mutation (C282Y) to confirm the clinical suspicion.

1) Fetal prenatal diagnosis. Straightforward DNA test in an at-risk fetus. Sources of fetal DNA include desquamated cells in the amniotic fluid (obtained during amniocentesis) or chorionic villi (chorion villus sampling' or CVS).

2) Preimplantation genetic diagnosis (PGD).

A few cells obtained from the developing preembryo allow genetic diagnosis in vitro (i.e., in vitro fertilization, or IVF). This allows early detection of an abnormality and avoids termination of pregnancy. PGD is still not robust enough to be routinely available.

1) Reproduction screening. DNA tests are undertaken to identify couples who are at risk for a genetic defect in the fetus. Presently, most reproduction screenings are undertaken because there is a family history, or because the couple demonstrates a risk factor (e.g., advanced maternal age).

2) Newborn screening. Newborns are screened for a number of genetic disorders that are treatable or preventable, provided they are diagnosed early.

3) Community screening. This involves the DNA testing of populations who have no prior risk. The populations can be whole communities (comparable to mammography screening for breast cancer) or selected communities.

An example of whole community testing would be DNA-testing all pregnant women for cystic fibrosis. A selected community screening program is exemplified by testing for Tay Sachs disease in Ashkenazi Jews.

1) Neurological adult-onset disorders. Huntington disease (HD) develops around the fourth decade of life. The DNA predictive test is used to identify whether an at-risk individual has inherited the mutant or normal gene from an affected parent. Although no treatment is available, the HD predictive test is useful because penetrance is very high in HD.

2) Cancers. Individuals with a high risk of familial breast cancer can have DNA testing of BRCA1 and BRCA2 genes to look for a mutation that might guide them in future treatment decisions, as well as identify risks in other family members. However, unlike genetic forms of colon cancer, such as familial adenomatous polyposis, the penetrance with BRCA1 and BRCA2 is quite variable (36-85% lifetime risk) and so understanding the significance of breast cancer gene mutations is not easy.


Table 1 Classes of DNA genetic tests (Continued)

DNA test and description

Individualizing—A form of DNA screening test involving drug metabolism pathways to predict a patient's response to treatment.'6-1 Unlike screening mentioned above, this type of test is directed to the individual.


1) Malignant hyperthermia. Individuals exposed to anesthetic agents can develop life-threatening complications if they have a genetic abnormality involving the ryanodine receptor genes (RYR1).'4]

2) Oral anticoagulation with warfarin. Side effects of anticoagulation treatment include life-threatening bleeding episodes. Two genetic variants of the important warfarin-metabolizing enzyme (hepatic microsomal enzyme CYP2C9) are associated with decreased enzymatic activity.'2-1

a more sophisticated approach to interpretation and greater resources to ensure that they are undertaken optimally. A final class that is not yet a component of routine practice is the potential to individualize treatment options to avoid drug-induced morbidity and mortality.'7-

DNA screening is worth considering in more detail because it will continue to remain topical for some time. Newborn screening is well accepted as an approach to detecting genetic or metabolic disorders for which intervention is possible, thereby preventing the disease or its consequences from developing. A good example is phenylketonuria. By identifying this early in the newborn, the development of mental retardation can be prevented by a phenylalanine-restricted diet. More controversial is DNA newborn screening for cystic fibrosis. Because there are no specific preventative measures, the value of this test has been questioned. However, it has been justified on the basis that the earlier detection of cystic fibrosis avoids anxiety and uncertainty in the parents if their child is ill and a diagnosis is not made. There is also some evidence that the long-term outlook is improved.'8-

Another type of DNA screening, which involves the testing of asymptomatic individuals in the community for recessive conditions, has provoked a lot of discussion. The article by Grody'4] notes that cystic fibrosis has the ''honor of being the first disease subject to nationwide, pan-ethnic molecular genetic screening.'' However, the National Institutes of Health (NIH) reference quoted specifically advises against cystic fibrosis genetic testing in the general population or newborns. Apart from DNA testing in those with a positive family history, the NIH consensus statement recommends cystic fibrosis DNA testing in couples planning a pregnancy or seeking prenatal care.'9] Despite this, the routine DNA testing of couples in relation to reproduction has not been adopted universally. Problems that need to be addressed include the logistics of pretest and posttest counseling. In multicultural societies, there is the additional consideration of risk variability and the optimal mutation profile is required. The latter is relevant for cystic fibrosis DNA testing, which has low sensitivity because of the large number of mutations present.

The potential utility for genomics on clinical decision making is illustrated by a microarray example, which allowed 295 patients with primary breast cancer to be studied by measuring the expression of 70 genes likely to influence the natural history.[10] These 70 genes involving cell cycle regulation, invasion, metastasis, and angiogen-esis were initially selected from a 25,000-gene array. Based on gene expression patterns, patients were stratified into high-risk and low-risk groups. It was claimed that this was a more powerful predictor of clinical outcomes in breast cancer than conventional clinical or histopathological criteria. Decisions about benefits patients would derive from adjuvant treatment (hormonal or chemotherapy) could then be based on more objective data.[10]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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