Novel 327bp Alu element insertion in LDLR exon 17 causes alternative splicing and familial hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH) is a severe form of familial hypercholesterolemia (FH), characterized by high low-density lipoprotein cholesterol (LDL-C) levels and increased coronary artery disease risk. This study reports a novel Alu insertion in the LDLR gene in a consanguineous Indian family, causing FH.

Objective: To identify and characterize the mutation causing HoFH in a proband and their family members.

Unprecedented Co-occurrence: Identification of a Pathogenic Genetic Variant in the KMT2B Gene in a Wilson Disease Patient with a Pathogenic ATP7B Mutation.

The pathophysiology of dystonia in Wilson disease (WD) is complex and poorly understood. Copper accumulation in the basal ganglia, disrupts dopaminergic pathways, contributing to dystonia's development via neurotransmitter imbalance. Despite advances in diagnosis and management, WD with dystonia remains a challenging condition to treat.

The Genomic Landscape of Wilson Disease in a Pan India Disease Cohort and Population-Scale Data.

Background: Wilson's disease (WD) results from pathogenic ATP7B gene variations, causing copper accumulation mainly in the liver, brain, and kidneys.

Objectives: In India, despite studies on ATP7B variants, WD often goes undiagnosed, with the prevalence, carrier rate, and mutation spectrum remaining unknown.

Methods: A multicenter study examined genetic variations in WD among individuals of Indian origin via whole exome sequencing.

Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments.

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake.

SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function.

In this study, we characterize a novel lncRNA-producing gene locus that we name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation and cardiovascular function. A 12-bp deletion of the scar-6 locus in zebrafish (scar-6) results in cranial hemorrhage and vascular permeability. Overexpression, knockdown and rescue with the scar-6 lncRNA modulates hemostasis in zebrafish.

Understanding the variant landscape, and genetic epidemiology of Multiple Endocrine Neoplasia in India.

Purpose: Multiple Endocrine Neoplasia (MEN) is a group of familial cancer syndromes that encompasses several types of endocrine tumors differentiated by genetic mutations in RET, MEN1 and CDKN1B genes. Accurate diagnosis of MEN subtypes can thus be performed through genetic testing. However, MEN variants remain largely understudied in Indian populations.

Spectrum of rare and common mitochondrial DNA variations from 1029 whole genomes of self-declared healthy individuals from India.

Mitochondrial disorders are a class of heterogeneous disorders caused by genetic variations in the mitochondrial genome (mtDNA) as well as the nuclear genome. The spectrum of mtDNA variants remains unexplored in the Indian population. In the present study, we have cataloged 2689 high confidence single nucleotide variants, small insertions and deletions in mtDNA in 1029 healthy Indian individuals.

Forward genetic screen using a gene-breaking trap approach identifies a novel role of -associated RNA transcript () in zebrafish heart function.

LncRNA-based control affects cardiac pathophysiologies like myocardial infarction, coronary artery disease, hypertrophy, and myotonic muscular dystrophy. This study used a gene-break transposon (GBT) to screen zebrafish () for insertional mutagenesis. We identified three insertional mutants where the GBT captured a cardiac gene.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

Introduction: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants.

The genomic landscape of variation in the Indian population.

The gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. The authors investigated the diversity and distribution of alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile.

Scalable noninvasive amplicon-based precision sequencing (SNAPseq) for genetic diagnosis and screening of β-thalassemia and sickle cell disease using a next-generation sequencing platform.

β-hemoglobinopathies such as β-thalassemia (BT) and Sickle cell disease (SCD) are inherited monogenic blood disorders with significant global burden. Hence, early and affordable diagnosis can alleviate morbidity and reduce mortality given the lack of effective cure. Currently, Sanger sequencing is considered to be the gold standard genetic test for BT and SCD, but it has a very low throughput requiring multiple amplicons and more sequencing reactions to cover the entire HBB gene.

Investigation of RFC1 tandem nucleotide repeat locus in diverse neurodegenerative outcomes in an Indian cohort.

An intronic bi-allelic pentanucleotide repeat expansion mutation, (AAGGG), at AAAAG repeat locus in RFC1 gene, is known as underlying genetic cause in cases with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and late-onset sporadic ataxia. Biallelic positive cases carry a common recessive risk haplotype, "AAGA," spanning RFC1 gene. In this study, our aim is to find prevalence of bi-allelic (AAGGG) in Indian ataxia and other neurological disorders and investigate the complexity of RFC1 repeat locus and its potential association with neurodegenerative diseases in Indian population-based cohorts.

genotyping of blood group alleles using WGS data: a comparative study of the Orang Asli in Peninsular Malaysia.

Differences in the distribution of RBC antigens defining the blood group types among different populations have been well established. Fewer studies exist that have explored the blood group profiles of indigenous populations worldwide. With the availability of population-scale genomic datasets, we have explored the blood group profiles of theOrang Aslis, who are the indigenous population in Peninsular Malaysia and provide a systematic comparison of the same with major global population datasets.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation.

Background: Maternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts.

Objectives: This study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation.

Methods: A diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.

Mitochondrial calcium signaling mediated transcriptional regulation of keratin filaments is a critical determinant of melanogenesis.

Mitochondria are versatile organelles that regulate several physiological functions. Many mitochondria-controlled processes are driven by mitochondrial Ca signaling. However, role of mitochondrial Ca signaling in melanosome biology remains unknown.

G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters.

The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription.

The genome sequence of lumpy skin disease virus from an outbreak in India suggests a distinct lineage of the virus.

Although previously confined to regions within Africa, lumpy skin disease virus (LSDV) infections have caused significantly large outbreaks in several regions of the world in recent years. In 2019, an outbreak of the disease was reported in India with low rates of morbidity and no reported mortality. However, in 2022, an ongoing outbreak of LSDV spanning over seven states in India resulted in the loss of over 80,000 cattle over a period of three months.