Focused Exome Sequencing Gives a High Diagnostic Yield in the Indian Subcontinent.

The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis.

Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy in Patients Clinically Suspected of FSHD Using Optical Genome Mapping.

Background And Objectives: Facioscapulohumeral muscular dystrophy (FSHD) represents the third most common muscular dystrophy in the general population and is characterized by progressive and often asymmetric muscle weakness of the face, upper extremities, arms, lower leg, and hip girdle. In FSHD type 1, contraction of the number of D4Z4 repeats to 1-10 on the chromosome 4-permissive allele (4qA) results in abnormal epigenetic derepression of the gene in skeletal muscle. In FSHD type 2, epigenetic derepression of the gene on the permissive allele (4qA) with normal-sized D4Z4 repeats (mostly 8-20) is caused by heterozygous pathogenic variants in chromatin modifier genes such as , , or .

Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.

Aim: Chromosome analysis of prenatal samples and products of conception (POC) has conventionally been done by karyotyping (KT). Shortcomings of KT like high turnaround time and culture failure led to technology innovations, such as the bacterial artificial chromosomes (BAC)s-on-Beads (BoBs)-based tests, Prenatal BoBs (prenatal samples) and KaryoLite BoBs (POC samples). In the present study, we validated and evaluated the utility of each test on prenatal, POC and blood samples.

Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains.

Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes.

Impact of occupational health hazards on serum markers of bone formation in spray painters of Chennai region in Tamil Nadu.

Context: The association between spray paint exposure and bone remodeling received little attention despite the high usage of spray paints in automobile industries, steel furniture workshops etc.

Aim: The present study was aimed at investigating the level of serum markers of bone formation in spray painters. The spray painting subjects were selected from automobile body repair workshops in Chennai region of TamilNadu which constitutes 30% of India's automobile industry.

Arterial blood gases, electrolytes, and metabolic indices associated with hemorrhagic shock: inter- and intrainbred rat strain variation.

We have previously shown interstrain variation (indicating a genetic basis), and intrastrain variation in survival time after hemorrhage (STaH) among inbred rat strains. To assist in understanding physiological mechanisms associated with STaH, we analyzed various arterial blood measures (ABM; pH, Paco2, oxygen content, sodium, potassium, glucose, bicarbonate, base excess, total CO2, and ionized calcium) in inbred rats. Rats from five inbred strains (n = 8-10/strain) were catheterized and, ≈ 24 h later, subjected to a conscious, controlled, 47% hemorrhage.

Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP.

Thymoquinone (TQ) is a bioactive component derived from the medicinal plant Nigella sativa. Recent studies reported that TQ exhibited cytotoxic effects in several cancer cell lines. Currently, no information in the literature is found concerning its mechanisms and cytotoxicity on neuroblastoma cells.

Life or death? A physiogenomic approach to understand individual variation in responses to hemorrhagic shock.

Severe hemorrhage due to trauma is a major cause of death throughout the world. It has often been observed that some victims are able to withstand hemorrhage better than others. For decades investigators have attempted to identify physiological mechanisms that distinguish survivors from nonsurvivors for the purpose of providing more informed therapies.

Myocilin mutations among POAG patients from two populations of Tamil Nadu, South India, a comparative analysis.

Purpose: Primary open angle glaucoma (POAG) is the most common type of glaucoma. Among the POAG genes identified so far, myocilin (MYOC) is the most frequently mutated gene in POAG patients worldwide. The MYOC Gln48His mutation is unique among Indian POAG patients.

Genetic influences on survival time after severe hemorrhage in inbred rat strains.

To find a genetic basis for differential ability to survive severe hemorrhage, we previously showed eightfold differences in survival times among inbred rat strains. We assumed that rat strains had similar normalized blood volumes (NBV; ml/100 g body wt). As NBV might vary among strains and constitute one genetic variable affecting survival time to hemorrhage, in experiment 1 of the current studies we first measured total blood volumes and calculated NBV in specific inbred rat strains (Brown Norway/Medical College of Wisconsin, BN; Dark Agouti, DA; Fawn Hooded Hypertensive, FHH; Lewis, LEW; and Dahl Salt-Sensitive, SS) previously found to be divergent in survival time.

Identification of HDM2 as a regulator of VEGF expression in cancer cells.

Overexpression of vascular endothelial growth factor (VEGF) and the extent of neoangiogenesis are closely correlated with tumor development and cancer metastases. To assess whether VEGF mediated angiogenesis is regulated by HDM2, we treated the GI-101A and HL-60 cells with HDM2 gene specific antisense phosphorothioate oligodeoxynucleotide (AS5). The antisense treatment resulted in a significant reduction of both basal as well as phorbol 12,13-dibutyrate (PDB) and Diethylstilbestrol (DES) induced VEGF mRNA and protein expressions.

Detection of HDM2 and VEGF co-expression in cancer cell lines: novel effect of HDM2 antisense treatment on VEGF expression.

The human homologue of murine double minute 2 (HDM2) oncogene is amplified in approximately 7% of all human cancers. Overexpression of HDM2 protein impairs cell cycle control and confers growth advantage to cancer cells. In several cancers the progression of tumor growth and formation of distant metastases are found to be dependent on tumor angiogenesis, a process that is regulated by vascular endothelial growth factor (VEGF).

Myocilin mutations among primary open angle glaucoma patients of Kanyakumari district, South India.

Purpose: Glaucoma can be defined as optic neuropathy leading to irreversible blindness if not treated in time. Primary open angle glaucoma (POAG) is the most common form of glaucoma. The myocilin (MYOC) gene has been found to mutate in both sporadic and familial cases of POAG worldwide.