BITS Pilani

  • Page last updated on Saturday, December 31, 2022



Molecular Genetics

We are primarily interested in understanding the molecular basis of susceptibility to complex diseases. Towards this goal, we develop and use cell-based models by using transgenic techniques or by treatment with disease-inducing agents. We are presently focusing on neurological disorders and oral cancer. Using our experience in genetic analysis, we also strive to develop reliable and better diagnostic tools for infectious and genetic diseases. A brief description of the currently active research areas.
Schizophrenia (SZ):

SZ is a complex disorder with an incidence of ~1% in different populations in the world. Although exact etiology is not established, genetic, epigenetic, chemical imbalance, brain structural abnormalities and environmental factors are implicated. The genetic susceptibility of SZ is six-times more than its general incidence. We are investigating the association of copy number variants (CNVs) and SNPs with SZ in Indian patients using Illumina PsychArrays and extensive bioinformatics using machine learning and artificial intelligence to identify patterns with higher predictive/diagnostic value.

Human Genetics

Genome-wide studies in patients and controls have suggested a number of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) among Caucasian studies. Till date, there is only one genome-wide study from India studying the SNPs and none on the CNVs. We developed i-MLPA, an improved method of CNV detection and showed that CNVs of 15q11.2 (BP1-BP2) region are not associated with schizophrenia among Indian patients. This CNV is a variant of uncertain significance and its association with an abnormality is not clear. We also conducted the largest CNV study involving this CNV in collaboration with Baylor College of Medicine and University of Pittsburgh Medical Center and showed that deletions are associated with dysmorphic features. Currently, we are studying CNVs of 15 regions that stand a higher probability of confirming in replication studies among Indian patients.
15q11.2 region
Infinium PsychArray Analysis of SNPs identified for neurological disorders
We have been screening 50,000 SNPs associated with neurological disorders, tag SNPs and exon SNPs in schizophrenia patients and controls using Infinium PsychArrays with an aim to replicate the disease-associated variants with schizophrenia patients in India. Initial data suggests that the variants reported in Caucasian patients are not likely to be confirmed in the Indian patients. In a pilot study, we have identified ~320 variants with a high promise of replication in a larger size sample. Data is being generated to confirm many novel variants that were identified in patients.
Stem cell Models
(A) DNMT1 overexpression, schizophrenia and other neurological disorders.

High discordance rates between monozygotic twins indicate epigenetic mechanisms in SZ. Of the main modifications of the epigenome, we currently focus on DNA methylation aberrations and dysregulation of DNA methylation machinery, particularly DNA methyltransferase 1 (DNMT1). Overexpression of DNMT1 is associated with SZ, bipolar and epilepsy disorders but the molecular basis of DNMT1 overexpression and its relationship with abnormal neurodevelopment is unknown. Since DNMT1 overexpression results in mid-gestational lethality, we have developed genetically modified mouse embryonic stem cells that overexpress different levels of DNMT1 (400% and 200%) and investigating their neurodevelopmental abnormalities using genome-wide methylation and transcriptome analysis. The obtained results are being explored further to delineate the mechanisms underlying SZ and other neurodevelopmental disorders such as epilepsy, autism, bipolar disorders and neurodegenerative disorders like multiple sclerosis, Huntington’s, etc.

Suggested Reading (For more information, click!):
  1. Saxena S. et al. Improved multiplex ligation-mediated probe amplification for rapid copy number variant (CNV) detection. Clinica Chimica Acta. 450: 19-24.
  2. Saxena S. et al. Analysis of 15q11.2 CNVs in an Indian population with schizophrenia. Annals of Human Genetics. 83: 187-191.
  3. Mohan KN. Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders. Stem Cells International. 2016: 4379425.
  4. Addepalli et al. CalPen (Calculator of Penetrance), a web-based tool to estimate penetrance in complex genetic disorders. PLosOne. 15: e0228156.
  5. Saxena et al. Analysis of transcript levels of a few schizophrenia candidate genes in neurons from a transgenic mouse embryonic stem cell model overexpressing DNMT1. Gene. 757: 144934.
  6. Saxena et al. Dysregulation of schizophrenia-associated genes and genome-wide hypomethylation in neurons overexpressing DNMT1. Epigenomics. 13: 1539-1555.
Oral Cancer:

Quick Links

    An Institution Deemed to be University estd. vide Sec.3 of the UGC Act,1956 under notification # F.12-23/63.U-2 of Jun 18,1964

    © 2023 Centre for Software Development,SDET Unit, BITS-Pilani, India.

    Designed and developed by fractal | ink design studios