Ankit Verma

University of Cambridge | Cam · Wellcome Trust/Cancer Research UK Gurdon Institute

Background Beckwith–Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively. In both of these diseases a subset of the patients is affected by multi-locus imprinting disturbances (MLID). In several families...

Background The prevalence and genetic spectrum of cardiac channelopathies exhibit population-specific differences. We aimed to understand the spectrum of cardiac channelopathy-associated variations in India, which is characterised by a genetically diverse population and is largely understudied in the context of these disorders. Results We utilised...

Background Imprinting Control Regions (ICRs) are CpG-rich sequences acquiring differential methylation in the female and male germline and maintaining it in a parental origin-specific manner in somatic cells. Despite their expected high mutation rate due to spontaneous deamination of methylated cytosines, ICRs show conservation of CpG-richness and...

ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and...

Background: PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility,...

Background: Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses: in the devastating gestationa...

Background: A subset of individuals affected by imprinting disorders displays multi-locus imprinting disturbances (MLID). MLID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (gDMRs) in early embryogenesis. Pedigrees of individuals with MLID also incl...

Zebrafish is increasingly being used to study liver injury and regeneration. However, very little is known about molecular players that respond to injury and those important for liver regeneration. We use a metronidazole nitroreductase (MTZ-nfsb)-based system to selectively ablate hepatocytes in adult zebrafish to create a model for liver injury an...

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 u...

Objective: This study systematically aims to evaluate the salivary microbiome in patients with primary Sjögren's syndrome(pSS) using 16S rRNA sequencing approach. Methods: DNA isolation and 16S rRNA sequencing was performed on saliva of 37 pSS and 35 control (CC) samples on HiSeq 2500 platform. 16S rRNA sequence analysis was performed independen...

Background & Aims: Zebrafish is increasingly being used to study liver injury and regeneration. However, very little is known about molecular players that respond to injury and participate in liver regeneration. Here we aim to generate a temporal map of gene expression changes at injury and during regeneration of the adult zebrafish liver. Methods:...

Neuronal ceroid-lipofuscinosis (NCL) is a heterogeneous and rare lysosomal storage disorder characterized by the accumulation of autofluorescent materials-ceroid and lipofuscin-in the cytoplasm.¹ It is manifested as a progressive destruction of neuronal cells resulting in brain atrophy, loss of vision, and other neurodegenerative phenotypes.¹ Over...

Hypertrophic cardiomyopathy (HCM) is an inherited heart failure condition, mostly found to have genetic abnormalities, and is a leading cause of sudden death in young adults. Whole exome sequencing should be given consideration as a molecular diagnostic tool to identify disease-causing mutation/s. In this study, a HCM family with multiple affected...

Background Gene environment interactions leading to epigenetic alterations play pivotal role in the pathogenesis of Coronary Artery Disease (CAD). Altered DNA methylation is one such epigenetic factor that could lead to altered disease etiology. In this study, we comprehensively identified methylation sites in several genes that have been previousl...

Earthworms show a wide spectrum of regenerative potential with certain species like Eisenia fetida capable of regenerating more than two-thirds of their body while other closely related species, such as Paranais litoralis seem to have lost this ability. Earthworms belong to the phylum Annelida, in which the genomes of the marine oligochaete Capitel...

miRNAs annotated from E. fetida small RNA transcriptome and genome. (XLSX)

Flowchart of gene annotation and differential expression analysis. (EPS)

Annotation of nerve growth factor from E. fetida. (DOCX)

The mitochondrial genome of E. fetida. (EPS)

Analysis of paralogs in E. fetida miRNome. (XLSX)

Primers used in this study. (DOCX)

South Asia is home to ∼ 20% of the world population and characterized by distinct ethnic, linguistic, cultural and genetic lineages. Only limited representative samples from the region have found its place in large population-scale international genome projects. The recent availability of genome scale data from multiple populations and datasets fro...

Halomonas salina strain CIFRI1 is an extremely salt-stress-tolerant bacterium isolated from the salt crystals of the east coast of India. Here we report the annotated 3.45-Mb draft genome sequence of strain CIFRI1 having 86 contigs with 3,139 protein coding loci, including 62 RNA genes. Citation Behera BK, Das P, Maharana J, Paria P, Mandal SN, Mee...

Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing as a rapid and efficient diagnostic strategy in several genodermatoses. The aim of this study was to explore the potential of molecular studies in dystrophic epidermolysis bullosa in India. Whole exome sequencing was performed using genomic DN...

Epidermolysis Bullosa (EB) encompasses a number of genetic conditions caused by mutations in genes involved in the formation of basement membrane resulting in blistering of the epidermis on trauma or pressure. At least 18 genes and 30 distinct subtypes of the disease are presently known[1]. Here‐in, we report two un‐related children with recessive...

Background: RNA is known to play diverse roles in gene regulation. The clues for this regulatory function of RNA are embedded in its ability to fold into intricate secondary and tertiary structure. Results: We report the transcriptome-wide RNA secondary structure in zebrafish at single nucleotide resolution using Parallel Analysis of RNA Structu...

Mitochondria are organelles involved in a variety of biological functions in the cell, apart from their principal role in generation of ATP, the cellular currency of energy. The mitochondria, in spite of being compact organelles, are capable of performing complex biological functions largely because of the ability to exchange proteins, RNA, chemica...

Aim: Adverse drug reactions to 5-Fluorouracil(5-FU) is frequent and largely attributable to genetic variations in the DPYD gene, a rate limiting enzyme that clears 5-FU. The study aims at understanding the pharmacogenetic landscape of DPYD variants in south Asian populations. Materials & methods: Systematic analysis of population scale genome wi...

Liver plays a key role in maintaining glucose homeostasis and impaired hepatic glucose metabolism is associated with type 2 diabetes. In the present study, we used RNA sequencing to profile the transcriptome of the livers of diabetic db/db mice as compared to the normal db/+ mice and identified 218 differentially expressed genes. Amongst these, the...

Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating...

Syndromes of mineralocorticoid excess (SME) are closely related clinical manifestations occurring within a specific set of diseases. Overlapping clinical manifestations of such syndromes often create a dilemma in accurate diagnosis, which is crucial for disease surveillance and management especially in rare genetic disorders. Here we demonstrate th...

X-linked agammaglobulinemia (XLA) is an extremely rare inherited primary immunodeficiency characterized by recurrent bacterial infections, decrease in number of mature B cells and low serum immunoglobulins. XLA is caused by mutations in the gene encoding Bruton's tyrosine kinase. We report a case of a young Indian boy suspected to have XLA. Immunop...

Earthworms show a wide spectrum of regenerative potential with certainspecies like Eisenia fetida capable of regenerating more than two-thirds of their bodywhile other closely related species, such as Paranais litoralis seem to have lost thisability. Earthworms belong to the phylum annelida, in which the genomes of the marineoligochaete Capitella t...

Long QT syndrome 10 is among the very rare forms of Long QT syndrome described sparingly. Phenotypically it is supposed to mimic LQTS 3 and is associated with sodium channel dysfunction due to defective Sodium Voltage-Gated Channel Beta Subunit 4 (SCN4B) gene. Here, we present a case of a boy from Punjabi family, presented with recurrent “seizures”...

Cardiomyopathies with ataxias are rare clinical presentations and often associated with a genetic etiology. Though there is no cure for the disease in many cases, clinical presentations can be managed if accurate diagnosis is made early in life. However the heterogeneity in both etiology and phenotype makes disease diagnosis often challenging. Here...

Dilated cardiomyopathy has known to have genetic basis implying the involvement of number of genes. Majorly, dilated cardiomyopathy is inherited in an autosomal dominant pattern. Familial cases of dilated cardiomyopathy could also inherit in an autosomal recessive, X linked or mitochondrial inheritance, making the accurate genetic diagnosis a tedio...

A functional vascular system is essential for the growth and development of vertebrates. Endothelial cells (ECs), which are key components of vasculature, create a semi- permeable barrier to control the supply of nutrients and oxygen to surrounding tissues. EC organization is modulated by various transcriptional cues. Aberrant regulation of these s...

Clinical diagnosis of autoinflammatory diseases requires a high degree of clinical suspicion and clinching molecular evidence to substantiate the diagnosis. This is more so in populations with low prevalence of these disorders. In this report, we describe the case of a young man from India with recurrent fever and persistent arthritis. The patient'...

Background: Junctional epidermolysis bullosa (JEB) is a diverse group of genodermatoses associated with extreme skin fragility. Despite several well-characterized genetic studies, molecular diagnosis of this heterogeneous group is still challenging. Recent advances in the field of genomics have seen the successful implementation of whole exome seq...

-linked agammaglobulinemia (XLA) is an extremely rare inherited primary immunodeficiency characterized by recurrent bacterial infections, decrease in number of mature B cells and low serum immunoglobulins. XLA is caused by mutations in the gene encoding Bruton's tyrosine kinase. We report a case of a young Indian boy suspected to have XLA. Immunoph...

Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID have been well documented. The widespread application of whole-exome...

LQTS 10 is among the very rare forms of LQTS described sparingly. Phenotypically it is supposed to mimic LQTS 3 and is associated with sodium channel dysfunction due to defective gene SCN4B. We present a case of a 2 year old boy and his mother having SCN4B mutation with the child having congenital complete heart block (CCHB) and documented LQTS.

Autoimmunity is a consequence of complex interactions between genes and the environment. Primary Sjogren’s syndrome(pSS) is a systemic autoimmune disease characterized by exocrine gland involvement resulting in sicca symtoms. The exact pathophysiology of the disease is not known. Szymula et al, 2014 demonstrated that a peptide derived from oral mic...

Syndromes of mineralocorticoid excess (SME) are closely related clinical manifestations occurring within a specific set of diseases. Overlapping clinical manifestations of such syndromes often create a dilemma in accurate diagnosis, which is crucial for disease surveillance and management especially in rare genetic disorders. Here we demonstrate th...

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB c...

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB c...

The organization of structure and function of cardiac chambers in vertebrates is defined by chamber-specific distinct gene expression. This peculiarity and uniqueness of the genetic signatures demonstrates functional resolution attributed to the different chambers of the heart. Altered expression of the cardiac chamber genes can lead to individual...

The zebrafish heart anatomy. (a) Cartoon of the adult zebrafish heart, (b) Dissected adult heart and the three chambers used for the present transcriptome analysis, (c) Atrium (d) Ventricle, (e) Bulbus arteriosus. Scale bar: 500μm. (TIF)

RNA isolated from the three cardiac chambers. (1) Atrium, (2) Bulbus arteriosus and (3) Ventricle used for the present transcriptome analysis. The RNA was isolated from pooled samples of individual chambers dissected from 15 animals. (TIF)

Real time qRT-PCR assay for cardiac chamber-restricted marker gene expression. The dissected cardiac chambers show specific marker genes expression. (A) Atrium, (V) Ventricle and (BA) Bulbus arteriosus. (a) myh6 and (b) vmhc were used as marker genes for the atrium and the ventricle respectively. The markers show restricted expression in individual...

KEGG pathway analysis. (DOCX)

Comparison of translational efficiency scores of the putative novel protein coding transcripts with respect to RefSeq protein coding and non coding transcripts. The box plot depicts the distribution of Translation Efficiency Scores (TES) across putative novel protein coding transcripts (34) identified in this study and RefSeq genes (coding and non...

Experimental validation of chamber-restricted differentially expressing protein coding genes. Ventricle-restricted genes (a) irx1a and (b) ldb3a, Atrium- restricted gene (c) vtg2, Bulbus arteriosus-restricted gene (d) rgs5a. (A) Atrium, (V) Ventricle and (BA) Bulbus arteriosus. Scale bar: 100 μm. See text for detailed information. (TIF)

List of gene primers. (DOCX)

List of genes differentially expressed in the zebrafish cardiac chambers and details on zebrafish mutants and human disease gene orthologs. (DOCX)

List of all putative novel protein coding gene loci identified in the present study. (DOCX)

Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in...

Rare genetic disorders are considered to be very rare in occurrence in the population but in reality the collective burden turned out to be the third health care burden in developing countries including India. Disease surveillance of these genetic disorders are preliminarily depends on the correct diagnosis and understanding molecular mechanism. In...

Lamellar ichthyosis (LI), considered an autosomal recessive monogenic genodermatosis, has an incidence of approximately 1 in 250,000. Usually associated with mutations in the transglutaminase gene ( TGM1), mutations in six other genes have, less frequently, been shown to be causative. Two siblings, born in a collodion membrane, presented with fish...

Background Dysbiosis has been hypothesized to play a role in the pathogenesis of autoimmune disease. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by sicca symptoms resulting from salivary and lacrimal gland dysfunction. This could result in dysbiosis of oral cavity. At the same time, dysbiosis could also be hypothesized t...

Halomonas salina strain CIFRI1 is an extremely salt-stress-tolerant bacterium isolated from the salt crystals of the east coast of India. Here we report the annotated 3.45-Mb draft genome sequence of strain CIFRI1 having 86 contigs with 3,139 protein coding loci, including 62 RNA genes.