1. GENETICS TESTING

2. How Are Genes Linked to Disease?
More than 4,000 diseases are thought to be caused by defective genes that are inherited from our parents.
When a gene contains a mutation, it encodes for a protein that is abnormal. Sometimes the changes are insignificant and sometimes
the changes can
be life
threatening.

3. What is Genetic Testing?
Genetic testing is where a person’s DNA is analyzed for abnormalities.
The abnormality can be very obvious, as in an extra or deleted chromosome.
Or the abnormality can be extremely small, such as the change
of one nitrogenous base.

4. Testing Genetic Material
Blood, urine, saliva, stool, body tissues, bone or hair can be analyzed.
Cells are isolated and the DNA within them is extracted and examined.

5. Some of the Uses of Genetic Testing
Newborn screening
Carrier testing
Predictive gene testing
Preimplantation screening
Confirmational diagnosis
Forensic testing
Parentage Testing
Molecular epidemiology of infectious diseases

6. Newborn screening for genetics diseases
Millions of babies are screened each year for genetic diseases
Abnormal arrangements of the bases of the genes or inborn errors of metabolism
Diseases screened vary by state. To see the tests conducted by state:

7. Carrier testing
Carrier testing identifies unaffected individuals who carry one copy of a gene that requires two to be expressed. These recessive genes (such as cystic fibrosis, sickle-cell anemia, or Tay-Sachs disease) cause serious, even fatal, consequences. Couples can learn their risk of passing these genes to their children.

8. Predictive gene testing
Identifies people who may be at risk for developing a disease, to include presymptomatic testing for adult-onset diseases (e.g. Huntington’s disease)
Identifies people who may be at risk for developing adult-onset cancers and Alzheimer’s disease.
Tests are currently available for at least two dozen different diseases. This number is expanding rapidly.

9. Preimplantation screening
Embryos used in intro-fertilization can be screened for genetic abnormalities, so that only mutation free embryos are implanted.

10. Confirmational diagnosis
Genetic testing can be used to confirm a suspected diagnosis of a genetic disorder.

11. Forensic testing
Genetic testing can be in forensics to establish identity of either the victim or the criminal.

12. Parentage Testing
The Paternity Index (PI) is determine. The higher the index, the higher the probability of paternity.
There are two assumptions made when one does paternity testing:
The mother is the true and real mother
No related male (of the reputed father) had sexual access prior to the gestation period.

13. Molecular epidemiology of infectious diseases
Blood banks routinely screen millions of units of blood each year for Hepatitis and HIV using nucleic acid testing.
Infectious disease specialists will use genetic testing for both diagnostic and epidemiologic applications

14. Identifying disease genes
The Human Genome Project mapped the sequences of human chromosomes. It mapped the order in which genes and or markers are found on chromosomes.
The target chromosome is broken into smaller pieces of DNA and the pieces are copied millions of times and then sent through a DNA sequencer

15. Predictive gene tests
These test look for disorders that “run in families”. This is due to the inheritance of a faulty gene.
Predictive tests are available for many genetic diseases.
The test can also show whether an individual has inherited tendencies to common cancers.

16. What are the benefits of gene testing?
Whether the test is negative or positive, genetic testing will alleviate a lot of the uncertainty.
A negative test may eliminate the need for further testing and checkups.
A positive test will allow the person to make informed decisions. A word of caution: A positive test does NOT guarantee that a disease will develop.

17. What are the limitations of gene testing?
There is not an answer for everyone! This field is still in its infancy and many questions are still unanswered.
Mutations can occur anywhere, and it is time consuming and costly to search long sections of DNA.
Clinical genetics tests are not just descriptive, but they are predictive as well. Thus. There is no yes/no answer, but the tests will tell probability.
Severity of a disease cannot be predicted.

18. What are the limitations of gene testing?
Severity of a disease cannot be predicted.
Many tests cannot detect all the variations that can cause a particular disease.
Many diseases are the result of the interaction between the environment and the genes.

19. What are the limitations of gene testing?
Keeping up with the advances is difficult. Many diseases lack optimal screening tests and the technology for early detection of some cancers is not available.

20. Techniques in molecular diagnosis
Target amplification systems
Polymerase chain reaction (PCR)
Transcription-mediated amplification (TMA)
Strand displacement
Probe amplification systems
Qβ replicase (QβR)
Ligase chain reaction (LCR)

21. Techniques in molecular diagnosis
Signal amplification system
Branched DNA probe (bDNA)
Signal detection-nonamplified
Nucleic acid probe

22. Advantages of molecular testing in diagnosis
Molecular diagnostic techniques were developed to improve detection of fastidious organisms or to provide a more rapid test result because:
Reliable diagnostic assays are not currently available
Molecular techniques offer enhanced detection sensitivity or specificity

23. Advantages of molecular testing in diagnosis
Molecular testing offers a savings in terms of time or reagents
Molecular testing offers a more rapid test results.. This is especially important for very slow growing organisms (e.g. Mycobacterium tuberculosis)

24. Polymerase Chain Reaction
PCR is the most commonly used molecular technique for the detection of infectious diseases
PCR is a primer mediated, temperature dependent technique for the enzymatic amplification of a specific DNA or RNA sequence.
It is used for the detection of viral, bacterial, parasitic or fungal pathogens.

25. Transcription Mediated Amplification
The procedure is based on the following two steps:
Synthesis of a cDNA molecule from an RNA target
Transcription using the cDNA as the template

26. Strand Displacement Amplification
The procedure is based on two enzymatic steps:
A restriction enzyme that creates a nick in the annealed primer
DNA polymerase replicates the nicked DNA

27. Qβ replicase (QβR)
Qβ replicase (QβR) is an RNA dependent RNA polymerase that is capable of amplifying RNA from Qβ phage.

28. Ligase Chain Reaction
 DNA amplification method similar to PCR. LCR differs from PCR because it amplifies the probe molecule rather than producing amplicon through polymerization of nucleotides.
LCR uses both a DNA polymerase enzyme and a DNA ligase enzyme to drive the reaction.
LCR can have greater specificity than PCR

29. Branched DNA probe (bDNA)
detects the presence of specific nucleic acids by measuring the signal generated by branched, labeled DNA probes

30. Nucleic Acid Probe
A nucleic-acid fragment that can be used to identify complementary segments present in the nucleic acid sequences of various microorganisms.

31. Conclusion
Genetics testing can be a mixed blessing. It is important to talk with a medical provider. Unlike other laboratory testing, genetics testing results may have implications not only for the patient, but family members as well. Therefore, genetics counseling is often advised.

32. References
Pfaller, Michael, “Molecular Approaches to Diagnosing and Managing Infectious Diseases: Practicality and Costs”,, on