Publications

Journal of infection and public health, Vol. 13, Issue 12, Pages 1920-1926, 2020

PMID: 33172818

First Zika virus (ZIKV) positive case from North India was detected on routine surveillance of Dengue-Like Illness in an 85-year old female. Objective of the study was to conduct an investigation for epidemiological, clinical and genomic analysis of first ZIKV outbreak in Rajasthan, North India and enhance routine ZIKV surveillance.

BMC medical genetics, Vol. 21, Issue 1, Pages 216, 2020

PMID: 33138774

To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS).

Epilepsy & behavior reports, Vol. 14, Pages 100397, 2020

PMID: 33196034

This study explores the etiology and lead time to treatment for infantile spasm (IS) patients and their effect on treatment responsiveness, in a limited resource setting. Patients with IS onset age ≤12 months', seen over 3 years were recruited retrospectively.

Nature Scientific reports, Vol. 10, Issue 1, Pages 17299, 2020

PMID: 33057012

Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions.

Pediatric nephrology (Berlin, Germany), Vol. 36, Issue 4, Pages 881-887, 2020

PMID: 33033857

Distal renal tubular acidosis (RTA) is typically caused by defects in ATP6V0A4, ATP6V1B1, and SLC4A1, accounting for 60-80% of patients. Genes recently implicated include FOXI1, ATP6V1C2, and WDR72, of which WDR72 is associated with dental enamel defects.

Epilepsy Res, Vol.166, Pages 106398, 2020

PMID: 32593896

A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE. An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification.

Nature communications, Vol. 11, Issue 1, Pages 4225, 2020

PMID: 32839463

Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile.

Frontiers in oncology, Vol. 10, Pages 1457, 2020

PMID: 32974170

Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer in India. Cigarette smoking and chewing tobacco are known risk factors associated with ESCC. However, genomic alterations associated with ESCC in India are not well-characterized.

Movement disorders clinical practice, Vol. 7, Issue 6, Pages 688-692, 2020

PMID: 32775516

Cerebellar ataxias, are a group progressively expanding spectrum of heterogeneous disorders. The clinical features and life expectancies are varied based on genetic and phenotypic presentations. 1 We present a familial case with an autosomal dominant inheritance of rapidly progressive ataxia with vocal cord palsy, due to D178N mutation in the PRNP gene.

PNAS, 117 (36) 22303-22310, 2020

PMID: 32817535

Penguins are the only extant family of flightless diving birds. They currently comprise at least 18 species, distributed from polar to tropical environments in the Southern Hemisphere. The history of their diversification and adaptation to these diverse environments remains controversial. We used 22 new genomes from 18 penguin species to reconstruct the order, timing, and location of their diversification, to track changes in their thermal niches through time, and to test for associated adaptation across the genome.

Journal of the American College of Cardiology, Vol. 76, Issue 6, Pages 703-714, 2020

PMID: 32762905

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

Trends in genetics : TIG, Vol. 36, Issue 10, Pages 804-806, 2020

PMID: 32768150

The Indian cobra genome comprises 38 chromosomes (2n) totaling 1.79 Gb with a GC content of ~40% and repeat content of 43%. The near-chromosomal assembly is highly contiguous with 95% of the genome represented by 19 large scaffolds that correspond to its chromosomes. The largest scaffold at ~375 Mb spans the entire chromosome 1. The genome codes for 23 248 predicted proteins and includes 139 venom toxins that target multiple physiological processes (Figure 1).

Nature Genetics, Sci Rep 10, 13100, 2020

PMID: 32753750

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial.

Journal of pediatric genetics, Vol. 10, Issue 1, Pages 23-28, 2020

PMID: 33552634

Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA- negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.

Parkinsonism Relat Disord, Vol. 74, Pages 33-35, 2020

PMID: 32305686

Ecol Evol, Vol. 10, Issue 11, Pages 4583-4594, 2020

PMID: 32551045

Knowledge of relationships in wild populations is critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, study genetic connectivity, study genotype-phenotype associations, trace individuals, or track wildlife trade, many identified individuals need to be genotyped at thousands of loci, mostly from noninvasive samples.

Nat Commun, Vol. 11, Issue 1, Pages 2056, 2020

PMID: 32345963

Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. By RNA-seq analysis, we identify a RET rearrangement in the tumour material of a patient who does not harbour any known RAS or BRAF mutations. This new gene fusion involves exons 1-4 from the 5' end of the Trk fused Gene (TFG) fused to the 3' end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner.

Microbial pathogenesis, Vol. 143, Pages 104131, 2020

PMID: 32169490

Cervical cancer is a growing and serious problem world-wide in women, but more acute in developing countries especially in Indian subcontinent. The main causative agent for the disease is Human Papilloma Virus (HPV). The history of the cervical cancer goes back to eighteenth century as the HPV infection is reported since 1800s.

Tuberculosis (Edinb), Vol 121, Pages 101915, 2020

PMID: 32279871

Tuberculosis is the leading cause of death among infectious diseases worldwide. Detection of Mycobacterium tuberculosis (Mtb), using routine culture-based methods is time consuming resulting in delayed diagnosis and poor treatment outcomes. Currently available molecular tests provide faster diagnosis but are able to screen only limited hot-spot mutations. Whole genome sequencing from direct sputum offers a potential solution, however, due to the presence of other microbes and host DNA its use in diagnostic testing remains challenging.

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion, Vol. 36, Issue 3, Pages 588-589, 2020

PMID: 32647443

Factor XIII deficiency is a rare inherited autosomal recessive disorder and occurs at a frequency of approximately 1 in 1–5 million people [1]. During the last 4 decades, over 200 cases of congenital factor XIII (FXIII) deficiency have been reported in the literature [2, 3]. FXIII circulates as a tetramer of two FXIIIA and two FXIIIB subunits.

Ophthalmic genetics, Vol. 41, Issue 1, Pages 99-100, 2020

PMID: 32077773

Horizontal gaze palsy with progressive scoliosis-1 (HGPPS1) is a rare autosomal recessive condition named after its clinical manifestations. HGPPS is due to ROBO3 mutation (OMIM number: 608630) and is characterized by brainstem maldevelopment which is responsible for its phenotypic presentation (1,2).

Cell reports, Vol. 30, Issue 5, Pages 1491-1503.e6. 2020

PMID: 32023464

How satellite cells and their progenitors balance differentiation and self-renewal to achieve sustainable tissue regeneration is not well understood. A major roadblock to understanding satellite cell fate decisions has been the difficulty of studying this process in vivo.

Immunobiology, Vol. 225, Issue 3, Pages 151907, 2020

PMID: 32044149

Epstein Barr Viral infection is a common childhood infection in India and is also nearly 100 % etiologically associated with pediatric Hodgkin Lymphoma (HL). The main question in EBV immunobiology has been, why only a small subset of infected individuals develop EBV associated malignancies, while the vast majority carry this virus asymptomatically for life.

Nephrology (Carlton, Vic.), Vol. 25, Issue 6, Pages 497-501, 2020

PMID: 31925849

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies.

Journal of clinical and experimental hepatology, Vol. 10, Issue 1, Pages 100, 2020

PMID: 32025170

[This corrects the article DOI: 10.1016/j.jceh.2018.08.002.].

European journal of human genetics : EJHG, Vol. 28, Issue 5, Pages 669-673, 2020

PMID: 31965066

The T-box4 (TBX4) gene (OMIM *601719) belongs to the T-box family of transcription regulators that share a conserved homology domain and are expressed at specific sites during various stages of embryonic development.

Molecular syndromology, Vol. 11, Issue 1, Pages 43-49, 2020

PMID: 32256301

We report a family with a spectrum of short stature, craniofacial dysmorphism, and digital anomalies in a father and 2 daughters, with the youngest (proband) displaying a severe phenotype. Clinically, autosomal dominant Robinow syndrome (ADRS) was diagnosed. Whole-exome sequencing identified a heterozygous pathogenic BMP2 variant in the father and his daughters.

Journal of clinical lipidology, Vol. 14, Issue 1, Pages 35-45, 2020

PMID: 32044282

Familial hypercholesterolemia (FH), an autosomal codominant disorder characterized by very high low-density lipoprotein cholesterol, is strongly associated with premature coronary artery disease.

Nature genetics, Vol. 52, Issue 1, Pages 106-117, 2020

PMID: 31907489

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near- chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake.

Breast cancer research : BCR, Vol. 21, Issue 1, Pages 152, 2019

PMID: 31881983

PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.

South Asian journal of cancer, Vol. 8, Issue 4, Pages 247-249, 2019

PMID: 31807490

Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA).

Nature Scientific reports, Vol. 9, Issue 1, Pages 18793, 2019

PMID: 31827134

Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge.

Molecular genetics & genomic medicine, Vol. 8, Issue 2, Pages e1081, 2019

PMID: 31816670

Studies evaluating next-generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India).

American journal of human genetics, Vol. 105, Issue 6, Pages 1254-1261, 2019

PMID: 31809748

Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans.

Nature, Vol. 576, Issue 7785, Pages 106-111, 2019

PMID: 31802016

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world's population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue.

Viral immunology, Vol. 32, Issue 10, Pages 430-441, 2019

PMID: 31800372

Women with persistent human papillomavirus (HPV) infections have a high risk of developing cervical cancer (CaCx). HPV-16 alone accounts for more than 60% of CaCx worldwide. Most of the HPV infections are transient and only a subset of women develop persistent HPV-16 infection.

Molecular Phylogenetics and Evolution, 2019

PMID: 31323335

In this study, we use genome-wide Single Nucleotide Polymorphisms to test genetic differentiation between these geographically isolated taxa and evaluate the main drivers of population structure among breeding colonies of macaroni/royal penguins. Genetic similarity observed between macaroni and royal penguins suggests they constitute a single evolutionary unit.

Nature Scientific reports, Vol. 9, Issue 1, Pages 14684, 2019

PMID: 31604989

This study investigated the potential of vitamin K1 as a novel lens aldose reductase inhibitor in a streptozotocin-induced diabetic cataract model. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, activation of lens aldose reductase 2 (ALR2) and accumulation of sorbitol in eye lens which could have contributed to diabetic cataract formation. However, when diabetic rats were treated with vitamin K1 (5 mg/kg, sc, twice a week) it resulted in lowering of blood glucose and inhibition of lens aldose reductase activity because of which there was a corresponding decrease in lens sorbitol accumulation.

Journal of Cancer Immunology Research, 7(10): 1714-1726, 2019

PMID: 31409607

Irreversible electroporation (IRE) is a nonthermal ablation technique that is used clinically in selected patients with locally advanced pancreatic cancer, but most patients develop recurrent distant metastatic disease. We hypothesize that IRE can induce an in situ vaccination effect by releasing tumor neoantigens in an inflammatory context. Using an immunocompetent mouse model, we demonstrated that IRE alone produced complete regression of subcutaneous tumors in approximately 20% to 30% of mice.

Cells, Vol. 8, Issue 9, 2019

PMID: 31438645

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form.

European journal of medical genetics, Vol. 63, Issue 3, Pages 103742, 2019

PMID: 31421288

THOC6 is a newly described causal gene for an autosomal recessive intellectual disability (ID) - Beaulieu Boycott Innes syndrome (BBIS) (OMIM # 613680). It is characterized by ID with dysmorphic facies, genitourinary, cardiac anomalies, and dentition problems. Here, we report the first two siblings of BBIS from the Indian subcontinent with previously unreported skeletal anomalies such as Sprengel shoulder, calcaneo valgus deformity, radioulnar dysostosis, and overlapping toes.

Pharmacogenomics, Vol. 20, Issue 10, Pages 719-729, 2019

PMID: 31368850

The CYP2D6 gene is highly polymorphic and harbors population specific alleles that define its predominant metabolizer phenotype. This study aimed to identify polymorphisms in Indian population owing to scarcity of CYP2D6 data in this population.

Annals of Indian Academy of Neurology, Vol. 22, Issue 2, Pages 231-233, 2019

PMID: 31007444

We describe an 11-month-old boy who presented with recurrent respiratory infections from 6 months of age. His elder sister died at 10 months with severe septicemia and meningitis. The boy had a mild motor delay. Investigations revealed T cell deficiency and very low serum uric acid suggestive of purine nucleoside phosphorylase (PNP) deficiency - a rare variant of severe combined immunodeficiency disease. A novel homozygous missense mutation of c.597C>G(p. S199R) of exon 5 on PNP gene confirmed the diagnosis. We suggest that uric acid should be a part of investigation profile for unidentified motor delay, as recurrent infections can be late presentation.

Frontiers in oncology, Vol. 9, Pages 435, 2019

PMID: 31192134

Urothelial carcinoma is the most common malignancy of the bladder and is primarily considered as a disease of the elderly. Studies that address bladder tumor occurrence in young age groups are rare.

Frontiers in plant science, Vol. 10, Pages 513, 2019

PMID: 31134103

Purpleputtu (Oryza sativa ssp. indica cv. Purpleputtu) is a unique rice landrace from southern India that exhibits predominantly purple color. This study reports the underlying genetic complexity of the trait, associated domestication and de-domestication processes during its coevolution with present day cultivars.

Biosensors & bioelectronics, Vol. 133, Pages 107-124, 2019

PMID: 30921627

Diabetes Mellitus (DM) is one among the supreme metabolic issues observed in history since 3000 BCE and has gained much interest recently due to the increasing number of diabetic cases every year. Glucose is considered as the most iconic biomarker for diabetes detection, and fluctuations in its levels are related to different stages of DM.

Frontiers in oncology, Vol. 9, Pages 221, 2019

PMID: 31058073

Retinoblastoma is a rare pediatric tumor of the retina, caused by the homozygous loss of the Retinoblastoma 1 (RB1) tumor suppressor gene. Previous microarray studies have identified changes in the expression profiles of coding genes; however, our understanding of how non-coding genes change in this tumor is absent.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Vol. 35, Issue 9, Pages 811-814, 2019

PMID: 30964350

Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study.

Pediatric hematology and oncology, Vol. 36, Issue 2, Pages 82-85, 2019

PMID: 30963792

A 2.5-year-old girl presented with redness and swelling of the right-eye for 7-days (Figure 1A). Examination revealed an intraocular mass with anterior segment seeding. The other eye was normal. A diagnosis of unilateral retinoblastoma (RB) manifesting as orbital cellulitis was considered

American journal of medical genetics. Part A, Vol. 179, Issue 6, Pages 1091-1097, 2019

PMID: 30908877

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway.

Movement disorders clinical practice, Vol. 6, Issue 3, Pages 267-268, 2019

PMID: 33999972

A 21‐year‐old man presented to us with involuntary jerking movements of his hands and head that started at the age of 13. In the early years, the movements would come in intermittent spells, and sometimes his whole body would tremble when anxious, concentrating on an activity, or riding his scooter.

Cancer immunology research, Vol. 7, Issue 2, Pages 174-182, 2019

PMID: 30679156

T-cell recognition of cancer neoantigens is important for effective immune-checkpoint blockade therapy, and an increasing interest exists in developing personalized tumor neoantigen vaccines. Previous studies utilizing RNA and long-peptide neoantigen vaccines in preclinical and early-phase clinical studies have shown immune responses predominantly driven by MHC class II CD4(+) T cells.

Parkinsonism & related disorders, Vol. 62, Pages 246-247, 2019

PMID: 30660597

Mutations in GNAL have been associated with cranio-cervical dystonia (DYT-GNAL) [ [1] ]. The dystonia most often progresses to involve other regions, particularly the face and laryngeal muscles and less commonly the trunk, arm and lower limbs. The clinical phenotype in GNAL-related dystonia appears to be similar to that caused by mutations in THAP1 [ [2] ]

Diabetes research and clinical practice, Vol. 148, Pages 189-199, 2019

PMID: 30641161

Epigenetic mechanisms regulate gene expression and may influence the pathogenesis of type 2 diabetes through the loss of insulin sensitivity. The aims of this study were to measure variation in DNA methylation at the type 2 diabetes locus KCNQ1 and assess its relationship with metabolic measures and with genotype.

Frontiers in immunology, Vol. 9, Pages 3017, 2018

PMID: 30622534

A large number of tumor intrinsic and extrinsic factors determine long- term survival in human cancers. In this study, we stratified 9120 tumors from 33 cancers with respect to their immune cell content and identified immunogenomic features associated with long-term survival.

FEBS letters, Vol. 593, Issue 1, Pages 23-41, 2018

PMID: 30417337

Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint- based reconstruction and analysis approaches to identify and explain RB- specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.

Cancer cell, Vol. 34, Issue 5, Pages 792-806.e5, 2018

PMID: 30449325

Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L.

Cells, Vol. 7, Issue 10, 2018

PMID: 30360455

Cardiovascular diseases (CVD) are still the prevailing cause of death not only in industrialized countries, but even worldwide. Type 2 diabetes mellitus (type 2 DM) and hyperlipidemia, a metabolic disorder that is often associated with diabetes, are major risk factors for developing CVD. Recently, clinical trials proved the safety of gliptins in treating patients with type 2 DM.

PloS one, Vol. 13, Issue 9, Pages e0203845, 2018

PMID: 30256815

Familial adenomatous polyposis (FAP) is an inherited condition arising from genetic defects in the Adenomatous polyposis coli (APC) gene. Carriers with mutations in the APC gene develop polyps in the colon and rectum which if not managed, transition into colon cancer. In this study, we identified a novel germline mutation in the APC gene in members of an FAP-affected (Familial adenomatous polyposis) family.

Parkinsonism & related disorders, Vol. 60, Pages 186-187, 2018

PMID: 30174277

Mutations in the myofibrillogenesis regulator gene (MR-1) causes paroxysmal non -kinesigenic dyskinesia (PNKD) characterized by episodic (paroxysmal) attacks of any combination of chorea, dystonia and athetosis (MR-1/PNKD) [1]. This gene is transcribed into three alternatively spliced isoforms: long (MR-1L), medium (MR-1M) and small (MR-1S) [2,3].

Nature Scientific reports, Vol. 8, Issue 1, Pages 12122, 2018

PMID: 30108227

Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70-80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families.

Nature Scientific reports, Vol. 8, Issue 1, Pages 10176, 2018

PMID: 29976937

Bestinopathies are a spectrum of retinal disorders associated with mutations in BEST1 including autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD). We applied whole-exome sequencing on four unrelated Indian families comprising eight affected and twelve unaffected individuals.

BMC medical genetics, Vol. 19, Issue 1, Pages 109, 2018

PMID: 29973161

Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion.

Animal biotechnology, Vol. 30, Issue 3, Pages 219-232, 2018

PMID: 29938580

Indigenous cattle of India belong to the species, Bos indicus and they possess various adaptability and production traits. However, little is known about the genetic diversity and origin of these breeds. To investigate the status, we sequenced and analyzed the whole mitochondrial DNA (mtDNA) of seven Indian cattle breeds.

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, Vol. 32, Issue 24, Pages 4177-4180, 2018

PMID: 29793366

Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain microdeletions which include cri-du-chat, DiGeorge, 1p36, Angelman, and Prader-Willi syndromes in comparison to the available screening methods.

Cancer biology & therapy, Vol. 19, Issue 9, Pages 773-785, 2018

PMID: 29723088

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood.

Becker's Hospital Review, 2018

Currently approved checkpoint inhibitors are antibodies that block the function of three key proteins expressed on the surface of T cells: CTLA-4, PD-1 and PD-L1. Under normal conditions, these proteins function as brakes to prevent immune-related toxicity from arising because of persistent T cell activity. Cancer hijacks this essential function   of immune homeostasis to protect itself from immune- mediated elimination [1, 2]. By expressing high levels of PD- L1, tumor cells engage PD-1 receptors on T cells, suppressing  their anti-tumor activity and escaping T cell-mediated killing. By blocking PD-1 and PD-L1 signaling, the checkpoint inhibitors remove the brakes on T cells imposed by the tumor and enhance their anti-tumor activity

Front Immunol, 16:9:188, 2018

PMID: 29527204

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells.

BMC medical genetics, Vol. 19, Issue 1, Pages 22, 2018

PMID: 29439679

Maturity-onset diabetes of the young (MODY) is an early- onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin.

Mitochondrial DNA. Part B, Resources, Vol. 3, Issue 1, Pages 207-208, 2018

PMID: 33490497

India has 40 distinct zebuine cattle breeds with different adaptability and production traits. In the present study, we report the complete mitochondrial genome sequence of Indian cattle for the first time. The mitogenome contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a control region (D-loop region).

Journal of obstetrics and gynaecology of India, Vol. 68, Issue 6, Pages 462-470, 2018

PMID: 30416273

Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India.

Nature Scientific Reports, Vol. 8, No. 851, 2018

PMID: 29339819

Jammu and Kashmir (J&K), the Northern most State of India, has been under-represented or altogether absent in most of the phylogenetic studies carried out in literature, despite its strategic location in the Himalayan region. Nonetheless, this region may have acted as a corridor to various migrations to and from mainland India, Eurasia or northeast Asia.

Lung Cancer (Auckland, N.Z.), Vol. 9, Pages 1-11, 2018

PMID: 29379323

Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC).

Molecular genetics & genomic medicine, Vol. 6, Issue 2, Pages 282-287, 2017

PMID: 29271071

Several genes have been implicated in a highly variable presentation of developmental delay with psychomotor retardation. Mutations in EMC1 gene have recently been reported. Herein, we describe a proband born of a consanguineous marriage, who presented with early infantile onset epilepsy, scaphocephaly, developmental delay, central hypotonia, muscle wasting, and severe cerebellar and brainstem atrophy.

Biosensors & bioelectronics, Vol. 103, Pages 143-150, 2017

PMID: 29291594

Methylglyoxal (MG) is a predominant precursor for advanced glycation end products (AGEs) due to its protein glycation reactions, which are the major causes of diabetic complications. MG is explored as a significant biomarker towards the prediction of diabetic complications.

Metabolic brain disease, Vol. 32, Issue 6, Pages 1901, 2017

PMID: 28875262

Experimental cell research, Vol. 361, Issue 2, Pages 333-341, 2017

PMID: 29097185

Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC).

Movement disorders clinical practice, Vol. 4, Issue 5, Pages 775-777, 2017

PMID: 30838287

Genetic Clinics 2017, Vol 10, Issue 1, 2017

Next generation sequencing has changed the approach to genetic diagnosis and testing in recent times. The days have arrived when a molecular genetic diagnosis can be attempted even without the availability of the proband or affected person. However this requires additional strong evidence of diagnosis in the proband, such as biochemical or radiological hallmarks. Needless to say, this attempt should always be made during counseling to make the family aware of the fallacies and limitation involved due to non-availability of the sample of the proband.

Omics : a journal of integrative biology, Vol. 21, Issue 5, Pages 295-303, 2017

PMID: 28481730

Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries.

American journal of medical genetics. Part A, Vol. 170, Issue 7, Pages 1868-1873, 2016

PMID: 27108999

We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a downstream stop codon and nonsense mediated decay. In the light of recent reports of HERC1 mutations in two families with a similar phenotypic presentation, this report reiterates the pathogenic nature and clinical consequences of HERC1 disruption. (c) 2016 Wiley Periodicals, Inc.

Nature genetics, Vol. 48, Issue 4, Pages 407-416, 2016

PMID: 26928227

We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct molecular subtypes: sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic- sarcomatoid (biphasic-S).

Biorheology, Vol. 53, Issue 1, Pages 33-47, 2016

PMID: 26889656

Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13.

Molecular vision, Vol. 22, Pages 73-81, 2016

PMID: 26900326

To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS.

Movement disorders clinical practice, Vol. 2, Issue 3, Pages 326-327, 2015

PMID: 30838237

Kufor-Rakeb syndrome (KRS; PARK 9) is a rare autosomal-recessive form of juvenile-onset Parkinson's disease (PD) caused by ATP13A2 gene mutations. The classical description of KRS is that of rapidly progressive symptoms in the form of parkinsonism, spasticity, supranuclear upgaze paresis, facial-faucial-finger minimyoclonus, visual hallucinations, oculogyric dystonic spasms, and dementia, usually noted between 12 and 16 years of age, resulting in early severe motor handicap.[1]

BioMed research international, Vol. 2015, Pages 940864, 2015

PMID: 25922843

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes.

Future oncology (London, England), Vol. 11, Issue 2, Pages 279-293, 2015

PMID: 25591839

Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development resulting in their approval. These new targeted therapies require patient selection and the discovery of biomarkers of response. This review discusses the evolution of targeted therapies in cancer and challenges in translating the concepts into clinical practice.

Frontiers in immunology, Vol. 5, Pages 546, 2014

PMID: 25400637

The M1 and M2 states of macrophage polarization are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. The M1/M2 paradigm is an excellent framework to understand and appreciate some of the diverse functions that macrophages perform. Molecular analysis of mouse and human macrophages indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. In this perspective, I discuss the function of recepteur d'origine nantais (RON) receptor tyrosine kinase in regulating the M2-like state of macrophage activation Besides decreasing pro- inflammatory cytokine production in response to toll-like receptor-4 activation, macrophage-stimulating protein strongly suppresses nitric oxide synthase and at the same time upregulates arginase, which is the rate limiting enzyme in the ornithine biosynthesis pathway. Interestingly, RON signaling preserved some of the characteristics of the M1 state, while still promoting the hallmarks of M2 polarization. Therefore, therapeutic modulation of RON activity can shift the activation state of macrophages between acute and chronic inflammatory states.

Journal of Antimicrobial Chemotherapy, Volume 69, Issue 12, Pages 3349–3355, 2014

PMID: 25085657

Increased trends of primary drug resistance mutations (DRMs) among treatment-naive HIV-1-infected patients in low- and middle-income countries (LMICs) and the non-availability of pre-antiretroviral therapy (ART) genotypic resistance testing (GRT) may severely affect future therapeutic outcomes. The main objective of this study was therefore to develop a simplified, cost- and labor-efficient but high-throughput GRT protocol to be applied in the large-scale surveillance of DRMs in LMICs.

Indian journal of human genetics, Vol. 20, Issue 2, Pages 175-184, 2014

PMID: 25400347

This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.