Genetic tests raise hope for humanity

Dr Mahesh Kandasamy | 10-August-2013

The DNA-based genetic tests are established scientific methods to identify the mutated gene. The process involves the isolation of genomic DNA and direct DNA sequencing is used to confirm the mutation in a particular gene

By Dr Mahesh Kandasamy

Hereditary diseases are carried by mutation in the single gene, multiple genes or mitochondrial DNA (Maternal). Inheritance of a specific disorder depends on the type of chromosome affected (Autosomal or sex chromosome). The inheritance pattern of mutations in autosomal chromosomes can be classified into autosomal dominant and autosomal recessive disorders. The inheritance pattern of mutations in sex chromosomes can be grouped into three categories namely X-linked dominant, X-linked recessive and Y-linked hereditary disorders.

Mutations in the identical gene or different gene can lead to the same disease phenotype. Some diseases may result from the interactions of several genes and the environment. Different mutations in different genes may predispose individuals to the same kind of disorders (Cancer, diabetes, heart disease and hypertension).  Neuro degenerative disorder like Huntington’s disease, carriers with expanded-intermediate range of CAG repeat number in the HTT gene, may not develop the disease but their children are at high risk of developing HD as the CAG repeat expansion increase from one generation to the next. In some sporadic cases, the defective gene might originate in first generation due to de nova mutation and the subsequent generation may continue to be affected by the disorder. An affected mother can pass the genetic disorder to children in mutations of the mitochondrial genome (Leber’s hereditary optic neuropathy) as female’s egg contributes to mitochondrial DNA in the foetus.

Genetic tests

The DNA-based genetic tests are established scientific methods that are available to identify the mutated gene. It involves the isolation of genomic DNA followed by the Polymerase Chain Reaction (PCR) using locus specific primers. Direct DNA sequencing is used to confirm the mutation in a particular gene. Genotyping can be performed on DNA extracted from the peripheral blood, tissues biopsies and amniotic fluid (Prenatal diagnosis).In genetic testing, it is very important that affected or unaffected carrier, parents of affected child, family members and caretakers are made aware of the testing procedure, the medical benefits and drawback of the test.  They may require counselling for emotional, ethical, legal, social, economical and healthcare needs for the specific disease.

Research and medical system

These hereditary disorders are increasingly recognised and pose considerable challenges to the research and medical system. The clinical phenotypes of these disorders are highly complex and diverse.  Even though there are a few available measures to manage the disease, there is no completecure. The treatment strategies are specific for each hereditary disease. Enriched environment, physical exercise, healthy nutrition and social interactions are often prescribed additionally to cope with the disease.

The major obstacle to develop novel therapy is largely due to incomplete understanding of the biology of the disease. The human genome project has helped us to identify a huge number of genes with defects. It further allows us to focus ongenotype–phenotype correlates of disease.

Strategies that are directed towards silencing the expression of defective genes and RNA interference are considered. Recent advances in induced pluripotential stem cell (iPSC) technology offers a promising research platform to study the biology of these genetic disorders.  Using human disease specific iPSC, gene correction strategies provide the future perspective to revert the monogenic mutated gene into its normal state.  

Pros & cons of genetic tests

Genetic tests have already dramatically improved lives. Some tests are used to clarify a diagnosis and direct a physician towards appropriate treatments while others allow families to avoid having children with devastating diseases or identify people at high risk for conditions that may be preventable. Aggressive monitoring for and removal of colon growths in those inheriting a gene for familial adenomatous polyposis, for example, has saved many live.

Commercialised gene tests for adult-onset disorders such as Alzheimer’s disease and some cancers are the subject of most of the debate over gene testing. These tests are targeted to healthy (Presymptomatic) people who are identified as being at high risk because of a strong family medical history for the disorder. The tests give only a probability for developing the disorder.One of the most serious limitations of these susceptibility tests is the difficulty in interpreting a positive result because some people who carry a disease-associated mutation never develop the disease. Scientists believe that these mutations may work together with other, unknown mutations or with environmental factors to cause disease.

A limitation of all medical testing is the possibility for laboratory errors. These might be due to sample misidentification, contamination of the chemicals used for testing, or other factors.


The author is a Research Scientist, Molecular Genetics Laboratory, Department of Psychiatry, National Institute of Mental Health and Neurosciences, (NIMHANS), Bengaluru.