Study using Next Gen Sequencing shows novel variations in common genetic disorders in the Indian population

Out of the 200 participants in a pilot-scale study conducted by Medgenome Labs in partnership with Sir Ganga Ram Hospital, 26% were found to be carriers of one or more rare genetic disorders, 6% were identified to be carriers for congenital deafness and 4.5% were observed to be carriers for cystic fibrosis

New Delhi: The advent of Next Generation Sequencing (NGS) has changed the way clinicians now diagnose and manage genetic disorders. This technology is currently at the forefront of genetic diagnosis in India and globally. NGS has not only changed routine diagnostics but has also helped in identifying novel mutations in common diseases in the Indian population. In one such research study,  MedGenome Labs, the leaders in genetic testing in India, in partnership with Sir Ganga Ram Hospital, New Delhi, conducted a pilot study 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 over a period of 22 months with a sample size of 200 unrelated individuals, in the North Indian population. After pre-test genetic counseling, the 200 individuals were screened for pathogenic variants in shortlisted 88 genes using NGS technology. These variants were classified as per the guidelines of the American College of Medical Genetics. The study was facilitated by MedGenome Laboratories Bangalore, who carried out the molecular analysis, using NGS and the data was re-analyzed at Sir Ganga Ram Hospital, New Delhi.
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 interesting 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.”
In today’s’ time, carrier screening is being implemented globally to decrease the burden of genetic disease in India. But carrier screening of couples is currently limited to genetic disorders with a high frequency, a positive family history or is majorly ethnicity-based. Currently, there is no carrier screening program available in India, except for limited screening for Thalassemia and Down syndrome  With the help of results of pilot studies like this, we can expect more research studies to be encouraged in the future and 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, Bangalore, “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.”
Techniques such as NGS are helping to reduce the burden of genetic disorders in India. Over the past few years, the cost of NGS also has come down significantly and continues to fall. More doctors are now aware of NGS and its benefits and relying on them for genetic diagnosis.
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. NGS which sequences the whole genome is better than targeted panels which would miss out on many mutations.  All high-risk couples such as in IVF pregnancies, consanguineous couples and those with the 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.”
 Expanded carrier testing is the need of the hour in a country like India, with a high population, high birth rate and a high rate of consanguinity. With the availability of advanced molecular technologies, like NGS, expanded genetic screening aims to identify carriers for a much larger group of genetic diseases, not limited only to ethnicity or those with a positive family history.  NGS can play a key role in reducing the burden of genetic diseases in India.