Queen Square Centre for Neuromuscular Diseases


CSIR - Centre for Cellular and Molecular Biology,  Hyderabad


CCMB Hyderabad

Lead PI
K. Thangaraj

K Thangaraj

Clinical neuromuscular expertise, patients and geographical region
Our Centre is a basic science research institute; we do not see patients directly. Our clinical collaborators evaluate patients, collect samples (blood and tissue) and send to us.

Genetics and preclinical science expertise and facilities
CSIR-CCMB (http://www.ccmb.res.in/) is a premier research organization involved in multidisciplinary R&D programmes across scientific disciplines of biological science for economic, environmental and societal benefits of mankind. These include; Genomics & Epigenomics, Developmental Biology, Cell & Stem Cell Biology, Ecology & Wildlife Conservation, Structural Biology, Microbes and Biology of Infection. CCMB has excellent research facilities, including; NGS & genotyping, tissue culture, FACS, Transgenic & gene knockout, microscopy, crystallography & NMR, etc. PI of the project has over two and half decade of expertise in the field of human genetics and made pioneering contributions in the field of population and medical genomics.

Summary of current research programmes
Thangaraj's studies, for the first time, provide evidence that the contemporary Indian populations descend from two divergent groups - Ancestral South Indians, and Ancestral North Indians (Nature, 2009) - who have admixed during the past 2,000 - 4,000 years, and for the last 2,000 years almost all populations have been practicing endogamy (American Journal of Human Genetics, 2013). Subsequently, he demonstrated that practice of endogamy had led to high frequency of population-specific recessive disease in India (Nature Genetics, 2017). In addition, he has mapped several novel genes that are associated with neuromuscular disorders of mitochondrial origin, cardiovascular diseases and male infertility.

Top five publications from the past five years:
Dhandapany PS, Razzaque Md A, Muthusami U, Kunnoth S, Edwards JJ, Mulero-Navarro S, Riess I, Pardo S, Sheng J, Rani DS, Rani B, Govindaraj P, Flex E, Yokota T, Furutani M, Nishizawa T, Nakanishi T, Robbins J, Limongelli G, Hajjar RJ, Lebeche D, Bahl A, Khullar M, Rathinavel A, Sadler KC, Tartaglia M, Matsuoka R*, Thangaraj K*, Gelb BD* (2014) RAF1 mutations cause dilated cardiomyopathy. Nat. Genet. 36: 635-639. (*equally directed the work).

Paramasivam A, Meena AK, Sundaram C, Pedaparthi L, Uppin MS, Jabeen SA, Jyothi V, Thangaraj K (2016) Novel mutation in C10orf2 associated with multiple mtDNA deletions and chronic progressive external ophthalmoplegia. Mitochondrion 26: 81-85.

Chaubey G, Ayub Q, Rai N, Prakash S, Mushrif-Tripathy V, Mezzavilla M, Pathak AK, Tamang R, Firasat S, Reidla M, Karmin M, Rani DS, Reddy AG, Parik J, Metspalu E, Rootsi S, Dalal K, Khaliq S, Mehdi SQ, Singh L, Metspalu M, Kivisild T, Tyler-Smith C, Villems R, Thangaraj K (2017) "Like sugar in milk": reconstructing the genetic history of the Parsi population. Genome Biol. 18: 110.

Nakatsuka N, Moorjani P, Rai N, Sarkar B, Tandon A, Patterson N, Bhavani GS, Girisha KM, Mustak MS, Srinivasan S, Kaushik A, Vahab SA, Jagadeesh SM, Satyamoorthy K, Singh L, Reich D, Thangaraj K (2017) The promise of discovering population-specific disease-associated genes in South Asia. Nat. Genet. 49: 1403-1407 (accompanied by cover image and Editorial).

Tamang R, Chaubey G, Nandan A, Govindaraj P, Singh VK, Rai N, Mallick CB, Sharma V, Sharma VK, Shah AM, Lalremruata A, Reddy AG, Rani DS, Doviah P, Negi N, Hadid Y, Pande V, Vishnupriya S, van Driem G, Behar DM, Sharma T, Singh L, Villems R, Thangaraj K (2018) Reconstructing the demographic history of the Himalayan and adjoining populations. Hum. Genet. 137:129-139.

How the new international Centre will benefit research and clinical programmes:
i. Clinicians, who perform clinical diagnosis of neuromuscular disorders of mitochondrial origin are very few in the country. This project would offer extensive training to the clinical fellows, who would bring the expertise to India.
ii. Enable the establishment of new pipeline NGS data analysis.
iii. Most of mutations that are associated with specific phenotype in rest of the world are most often absent in India and vice versa. This collaboration would help in sharing phenotype/genotype data between centres for better understanding of ancestry and disease.
iv. Most importantly, we envisage that this initiative will pave the way for long-term collaborations.