Pediatric restrictive cardiomyopathy (RCM) is the rarest in its group and accounts for only 2.5-5% of all the diagnosed cardiomyopathies in children. It is a relentless disease with poor prognosis, and heart transplantation is the only long-term treatment option. The aetiology of pediatric RCM varies and includes conditions such as endomyocardial fibrosis, storage disorder (Fabry's disease, MPS), drugs, radiation, post-cardiac transplantation and genetic. Genetic causes encompasses mutations in sarcomeric (troponin I and T, actin, myosin and titin) and nonsarcomeric protein-coding genes (Desmin, RSK2, lamin A/C and bcl-2-associated athanogene 3 (BAG3)). Inheritance of RCM could be autosomal dominant, autosomal recessive and X-linked. Here, we report a case of RCM in an adolescent girl, who was symptomatic with palpitations and breathlessness on exertion. The patient showed presence of rare variants in FLNC (c.5707G>A; p.Glu1903Lys) and BAG3 genes (c.610G>A; p.Gly204Arg). These two variants were detected individually in asymptomatic father and mother, respectively. FLNC gene codes for gamma filamin. These filamin proteins play important role in maintaining the structural integrity of the sarcomere. BAG3 is the main component of the chaperone-assisted selective autophagy (CASA) pathway. Mutant FLNC leads to the formation of protein aggregates which are cleared by an active protein quality control system including CASA pathway. For further verification, in silico protein-protein interaction was performed using online software and tools. The results showed evident interaction between FLNC and BAG3 with significant binding score (-826.6) between them.

Mungbean (Vigna radiata L. Wilczek) is one of the most important warm season food legumes which contributes significantly towards nutritional security and environmental sustainability. Marker-trait association (MTA) for agronomic characters offer opportunities to deploy marker-assisted breeding for genetic amelioration of crops. This investigation was carried out with an objective to decipher population genetic structure of diverse Vigna accessions and detect microsatellite loci linked to major agronomic traits for mungbean improvement. The study was initiated with 290 diverse Vigna accessions including wild and cultivated accessions. A mungbean yellow mosaic India virus (MYMIV)-resistant association mapping panel was constructed to minimize the effect of yellow mosaic disease on crop performance. Among these, 117 accessions including 55 cultivated and 63 wild accessions were found highly resistant to MYMIV. After multi-environment phenotyping, a panel of 70 MYMIV-resistant mungbean accessions was subjected to analysis for assessing the population genetic structure as well as MTA for important agronomic traits. There was sufficient genetic variation among the 70-mungbean genotypes as depicted by 91 microsatellite markers. Population genetic structure analysis grouped the genotypes into five subpopulations. The locus GMES0162 (LG4) was strongly associated with days to first flowering, whereas loci CEDG 035 (LG8), DMB SSR001 (LG6), DMB SSR008 (LG4) and CEDG 168 (LG11) were associated with pod number. These marker-trait associations will be helpful in genetic improvement of mungbean through molecular breeding.

SARS-CoV-2 pandemic has recently made the entire world come to a standstill. The number of cases in the world, especially India, have been increasing exponentially. The need of the hour is to assimilate as much data as possible to fast track the pipeline of bringing in new therapeutic tools against this fatal virus. In this brief communication, we aim to throw light on the various variants of the proteins involved heavily in the pathophysiology of COVID-19, namely Spike protein, ACE2, GRP78, TMPRSS2 and NSP-12. We also portray the molecular docking studies of these proteins with specific drugs that are currently being associated with the same. In our brief study, we come across a few key findings. First of all the combinations of the variants of spike protein and ACE2 binding show overall 25% unfavourable ΔΔG. Second, NSP12 is the most mutation prone among all the NSPs of the SARS-CoV-2 genome and the most common mutations are P323L and A97V. Third, we discovered the variants found in the Indian subpopulation that have greater binding with the currently investigated drugs.

Genetic factors play an important role in the pathogenesis of schizophrenia. Dysregulations in the dopaminergic system have long been known to play an influential role in the development of this disorder. Although a large number of studies have investigated the association between genetic polymorphisms in the genes involved in this system and the risk of schizophrenia, the results have been inconsistent. In this meta-analysis, we searched for publications in Ovid Medline, Embase, Web of Science (science citation index expanded), and PsycNET for articles published until January 2020. We identified case-control studies investigating the association between four common genetic polymorphisms (rs6277, rs1799732, rs1800497, and rs1801028) and the risk of schizophrenia. The studies were subsequently selected according to the predefined inclusion and exclusion criteria. The data extraction was conducted according to the PRISMA guidelines.We also assessed the quality of the studies and investigated publication bias using funnel plot and Egger's regression test. The association analysis was conducted in allelic, dominant, and recessive genetic models. Subsequently, bioinformatics analysis of the effect of the polymorphisms found to be significantly associated with schizophrenia on protein stability, posttranslational modifications, and 3D protein structure was conducted. This meta-analysis showed that Taq1A (allelic model: OR, 0.856, 95% CI, 0.734-0.998) has a protective effect against the development of schizophrenia. Further, it was found that this variant may decreaseANKK1protein stability. Further, this polymorphism was found to lead to the gain of modifications sites for ubiquitination (Ubi. score =-1.894) and methylation (Meth. score =-0.834). Several genetic factors contribute to the susceptibility of schizophrenia. The updated knowledge emerging from this meta-analysis showing the protective effect of rs1800497 polymorphism (Taq1A) can shed light on the role of Taq1A polymorphism in the susceptibility to schizophrenia and also pave way for further functional studies investigating the role of ANKK1 protein in the pathogenesis of schizophrenia.

Deficiency of uridine monophosphate synthase (DUMPS) is a lethal genetic disorder associated with early embryonic mortality. Murrah and Mehsana male buffaloes (n = 594) were screened for DUMPS by PCR-RFLP technique. A few Murrah buffalo male calves were found to be carriers of DUMPS in RFLP, which has not been reported earlier. On the Sanger sequencing, a novel A to G substitution mutation was identified in AvaI restriction recognition site of UMPS gene in buffaloes. This mutation hinders digestion of DNA by AvaI which leds to false positive results for DUMPS carrier in RFLP. The results indicated that genome sequencing must be performed before confirming results of RFLP in any new species. All the buffaloes that were tested had only wild-type genotype in exon 5 for DUMPS specific allele.

Congenital heart defects (CHD) affect 50% of Down's syndrome (DS) cases. This review focusses on the pathogenic molecular mechanism leading to the formation of DS-associated CHD along with the advancement of the emerging diagnostic techniques available for such patients in past few decades. We have shed light on the causative genes of DS-associated CHD that are located either on chromosome 21 or outside chromosome 21. Along with locus-specific mutation, numerous SNP and CNV, miRNA, use of maternal folic acid during pregnancy and signalling pathways are also reported to contribute to the formation of CHD in patients with DS. With the help of both these our understanding of pathogenic mechanism causing CHD in DS cases along with the availability of emerging technologies has facilitated a novel discovery that has ultimately provided a better treatment and management for such cases. Accurate diagnosis and treatment are now available with the introduction of CNV detection and NGS based approaches such as WES, WGS, target sequencing and sequencing of foetal cell-free DNA by the medical geneticist and cardiologist have now allowed further identification of familial recurrence risk and relatives who are at risk through genetic counselling, thereby providing reproductive options and improving proper care of DS-associated CHD. Further, gene-editing studies explore novel pathogenic mechanisms and signalling pathways in DS-associated CHD.

Dysregulated histone methylation has emerged as a recurring theme in multiple neuropsychiatric disorders. However, it is yet unclear whether the altered histone methylation is associated with aetiologic mechanisms or an outcome of disease manifestation. In this study, we examined the genomewide association studies datasets of three major psychiatric disorders, schizophrenia (SCZ), bipolar disorder (BIP), and major depression disorder (MDD), which represents a total of 231,783 cases and 425,444 controls, to clarify the relationship. Our gene-set enrichment analysis results identified statistically significant association of genes involved in three histone methylation biological processes with the three adult-onset psychiatric disorders, which is mainly driven by the histone H3K4 methylation pathway (GO: 0051568). Further analysis of histone H3K4 methylation pathway genes revealed a widespread role of the genes in brain function and disease; 29 (52%) and 41 genes (73.2%) were associated with at least one brain-related trait or brain disorder, respectively. Spatiotemporal gene expression analysis suggests that these pathway genes play a critical role during the prenatal period and are consistent regulators in the cerebral cortex throughout an individual's life. AUTS2, DNMT1 and TET2 are genes of particular interest due to their pervasive role in various aspects of brain function. Our findings support a critical aetiologic role of H3K4 methylation genes shared across SCZ, BIP and MDD, providing new direction for the development of epigenetically-focussed drugs targeting common causal factors of these devastating disorders.

Genetic differentiation among different natural populations of a species depends upon the environmental factors and the evolutionary forces that operate on them. In this study, seven Indian natural populations of D. bipectinata, two from north and five from south India, have been studied for their chromosomal inversion polymorphism. A total of nine paracentric autosomal inversions were recorded from these seven places but only three of them, present on the 2L, 2R and 3L were found to be cosmopolitan in distribution. In all the populations, the frequency of standard gene arrangement was found to be high than their respective cosmopolitan inversion gene arrangement. The average heterozygosity (Ho) of cosmopolitan inversions increases from north to south. There is a latitudinal cline in the distribution of three cosmopolitan inversion arrangements because their frequency increases with the decreasing latitude, i.e. from north to south India. A comparison of the genetic profile of two north Indian and five south Indian natural populations of D. bipectinata reveals the role of natural selection as well as bottleneck effect in the genetic structuring of these populations which may be due to their varying ecological conditions to which they are constantly encountered. Further, the presence of all kinds of paracentric inversions in individual populations was analysed following Poisson distribution to see whether these inversions occur randomly in natural populations or not and the results indicate that north Indian populations show the random occurrence of these inversions than the populations derived from the south.

Improving spikelet number without limiting panicle number is an important strategy to increase rice productivity. In this study, a spikelet number enhancing SPIKE-allele was identified from the aus subtype indica rice, cv. Bhutmuri, which has an identical japonica like corresponding sequence including a retrotransposon sequence, usually absent in indica genotypes, like IR64. An allele-specific singletube PCR-based codominant marker targeting an A/G single-nucleotide polymorphism (SNP) at the 3'UTR was identified for easier genotyping. The yield enhancing ability of the Bhutmuri-SPIKE allele carrying RILs and NILs over IR64-SPIKE allele carrying alleles was due to increased number of filled grains/panicle. More than three times higher abundance of SPIKE transcripts was observed in Bhutmuri and NILs carrying this allele compared with IR64 and its allele carrying NILs. Higher rate of photosynthesis at more than 900 μmolm-2s-1 light intensity and more than six small vascular bundles between the two large vascular bundles in the flag leaves of Bhutmuri and its allele carrying NILs were also observed. The identified SPIKE allele and the marker associated with it will be useful for increasing the productivity of rice by marker-assisted breeding.