Study based on Next Generation Sequencing sheds new light on genetic disorders among Indians

According to clinical experts, the technology has not only changed routine diagnostics but also helping to identify novel mutations in common diseases.

The efficacy of the technology was seen in playing a key role in a 22-month pilot study conducted by MedGenome Labs, a genomics and clinical data driven diagnostics and drug discovery research company, in partnership with Sir Ganga Ram Hospital, New Delhi.

The pilot study was to determine the carrier frequency and to look for any novel mutations seen in the Indian population for common genetic disorders.

The study was conducted with a sample size of 200 unrelated individuals, in the North Indian population.

After pre-test genetic counselling, the 200 individuals were screened for pathogenic variants in shortlisted 88 genes using NGS technology.

These variants were classified as per the guidelines of American College of Medical Genetics.

The study was facilitated by MedGenome Laboratories, who carried out the molecular analysis using NGS and the data was re-analyzed at Sir Ganga Ram Hospital.

Out of the 200 participants, 52 (26%) were found to be carriers of one or more rare genetic disorders, 12 individuals (6%) were identified to be carriers for congenital deafness and the 9 individuals (4.5%)  were observed to be carriers for cystic fibrosis.

Three individuals were detected to be carriers for Pompe disease.

This study showed a higher carrier frequency for these disorders which was contrary to the generally held view about their low prevalence in Asian Indians.

Another finding was that the disease causing variants observed for disorders, such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc. were different from what is seen in the Western population.

Thus, this pilot study highlights the importance of having a Genetic Variant Database for the Indian population.

Dr Sunita Bijarnia-Mahay, author and Senior Consultant, Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi said “This study brought surprises by detecting those genetic disorders like cystic fibrosis which were not thought to be common. In future, such NGS based screening tests will bring benefit to not only the young couples who would be planning a baby, but also the healthcare officials in charting out the prevention strategies for our Indian population.”

However, according to medical reports, currently, there is no carrier screening program available in India, except for limited screening for Thalassemia and Down syndrome.

The study partners believe that with the help of results of pilot studies like this, more research may be conducted in the future, which may help to identify the common pathogenic variants in various genetic disorders in Indians, who are a diverse ethnic population, and thus work towards reducing the burden of genetic disorders especially those with high mortality and morbidity.

According to Dr Sheetal Sharda, Senior Consultant in Clinical Genetics, MedGenome Labs, Bengaluru, “Couples may not even be aware that they could be carrying a genetic variant, which could lead to their unborn child developing a genetic disorder. In most cases, carriers of a genetic disorder are asymptomatic and may have no family history and unfortunately their carrier status is often confirmed only after an affected baby is born.”

According to Prof. IC Verma, Senior Consultant & Advisor, Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi, “In countries such as India with high rates of consanguinity and endogamy, there is inadequate data present on mutations in the community. All high risk couples such as in IVF pregnancies, consanguineous couples and those with previous history of abnormal babies must get carrier testing done before their next pregnancy to prevent the birth of babies with genetic disorders and reduce the associated socioeconomic burden.”

MedGenome, a founding member of GenomeAsia 100K, initiated to sequence 100,000 Genomes in the Asian Population to create gene-pool data for higher research purposes.