Laboratory Accreditation Standards and Guidelines for Nucleic Acid Detection and Analysis

1.2 Categorisation of Nucleic Acid-Based tests for human genetic disorders

Page last updated: 03 July 2006


Nucleic acid-based diagnosis of human disease arising from gene mutations falls into two major categories:
a) germline inherited disorders (eg cystic fibrosis) or
b) somatic cell disorders (eg the bcr-abl translocation in leukaemia).

Inherited disorders


In relation to human inherited disorders, laboratories must provide guidance (relevant for their particular community and circumstance) to the Level 1 and Level 2 grouping of DNA tests that they perform.


DNA testing for inherited disorders has an added complexity compared with many other areas of laboratory testing because the information generated has relevance not only for the person being tested but also for other family members. Some DNA tests for human inherited disorders simply require the patient’s verbal consent after the provision of appropriate information by a qualified practitioner. For other DNA tests involving inherited disorders, however, formal pre and post-test professional genetic counselling, as well as formal written consent and additional confidentiality procedures, are appropriate parts of the testing process and are required for optimal patient care.
For the purpose of this document, a distinction is drawn between two broad classes of medical DNA testing for inherited genetic disorders, as shown in Table 1.1.

Table 1.1 Levels of DNA testing

          Type of DNA test for an inherited genetic disorder

          Explanatory notesa

          Level 1 DNA test
          Included here would be:

          a) DNA testing for diagnostic purposes (eg the patient has clinical indicators or a family history of an established inherited disorder and DNA testing is being used to confirm the disorder) or any other DNA test that does not fall into level 2.

          b) Neonatal screening programs.
          Level 2 DNA test
          (ie the test has the potential to lead to complex clinical issues)
          DNA testing for which specialised knowledge is needed for the DNA test to be requested, and for which professional genetic counselling should precede and accompany the test. Predictive or presymptomatic DNA testing for conditions for which there are no simple treatment, would usually be included in this grouping. Specific written consent and counselling issues are associated with this grouping.

a The distinction between Level 1 (standard DNA test) and Level 2 (DNA test with potential complex issues) would usually be made by the doctor ordering the test, since that individual will be best placed to appreciate the short- term and long-term implications of the test for the patient and other family members.

The previous description of DNA testing for inherited genetic disorders — which used Class A and Class B categories — has not been followed in this version of the NPAAC standards and guidelines. Although some type of categorisation is necessary, feedback indicated that Class A and Class B were confusing (particularly when examples were given) because there were inconsistencies in reasons for choosing a particular class. Also, an example could move from one class to the other depending on use and circumstances. It is not possible to rigidly assign disorders to either Class A or Class B, and the definition of a ‘serious genetic disorder’ can vary, depending on the circumstances (Wertz and Koppers 2002).
In using the above Level 1 (standard DNA test) versus Level 2 DNA test (complex issues) categorisation, no examples are given because the implication of the test will vary. Thus, a test may be standard in one particular circumstance but complex in another. This confusion will only be resolved as knowledge about DNA genetic testing and its implications increases in the health profession.
Despite the above open-ended approach, this NPAAC document requires laboratories to review the categorisation of DNA tests for human inherited disorders. This determination is best undertaken with input from representative professional bodies. In this way, some guidance will be provided as to what constitutes a Level 1 or Level 2 DNA test. This guidance will take into consideration resources, current knowledge, circumstances, the type of condition being tested for and the implications of the DNA test result for the patient and family.
The review should include input from groups such as the professional colleges (eg the Royal Australasian College of Physicians, the Royal Australian College of General Practitioners, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists) and professional expert associations (eg the Human Genetics Society of Australasia). Rather than the review being undertaken by each individual laboratory, the process will be organised on a broader front. For example, public hospital laboratories might coordinate this process through their state health departments, utilising the broad experience and input described above. Large private laboratories may have the necessary resources to undertake a similar exercise. Smaller private laboratories could adopt the policy promulgated by larger laboratories or state health departments.

Somatic cell disorders

DNA testing for somatic cell disorders is usually undertaken to confirm a clinical diagnosis or to follow progress of a disease, and would be considered to be standard DNA testing (Level 1)