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Review
. 2019 Sep 25;14(1):52.
doi: 10.1186/s40246-019-0215-5.

Genomics of rare genetic diseases-experiences from India

GUaRDIAN Consortium; Sridhar Sivasubbu  1 , Vinod Scaria  2
Collaborators, Affiliations
Review

Genomics of rare genetic diseases-experiences from India

GUaRDIAN Consortium et al. Hum Genomics. .

Abstract

Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India.Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma.In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India.

Keywords: Diagnostics; GUaRDIAN; Genetic diversity; Genomics; IPSCs; India; Patient support; Rare disease; Zebrafish.

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Conflict of interest statement

  1. I.

    Sridhar Sivasubbu and Vinod Scaria have received an unrestricted educational grant from M/S Sanofi Genzyme Pvt Ltd. for training medical professionals in the area of clinical genomics.

  2. II.

    Sridhar Sivasubbu and Vinod Scaria collaborate with M/S Adams Genetics Pvt Ltd. and M/S Genique Lifesciences Pvt Ltd. for developing technologies for interpretation of genome-scale datasets.

  3. III.

    Sridhar Sivasubbu, Vinod Scaria, and Md Faruq have developed and transferred molecular assays for diagnosis of genetic diseases to M/S Lal Path Labs Pvt Ltd.

  4. IV.

    Sridhar Sivasubbu and Vinod Scaria have developed and transferred NGS-based assays and computational reporting engine for diagnosis of mitochondrial diseases to M/S Eurofins Clinical Genetics India Pvt Ltd.

Figures

Fig. 1
Fig. 1
The GUaRDIAN framework. Clinicians refer patients and family members to GUaRDIAN consortium following which the blood/DNA samples and complete clinical investigations are shared. The samples undergo next generation sequencing, bioinformatic analyses, and variant prediction. The predicted genetic variant is checked for segregation in the family members using capillary sequencing. If a known pathogenic variant is identified, a research report is generated and sent back to the clinician. When a putative novel variant is identified, the effect of the genetic variant is modeled in a suitable system to validate the functionality of the variant and also to understand the disease mechanism. Further, the genetic variant information derived from patient/family is made available for community-level screening
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