Variant Classification for Pompe disease; ACMG/AMP specifications from the ClinGen Lysosomal Diseases Variant Curation Expert Panel.

Accurate determination of the clinical significance of genetic variants is critical to the integration of genomics in medicine. To facilitate this process, the NIH-funded Clinical Genome Resource (ClinGen) has assembled Variant Curation Expert Panels (VCEPs), groups of experts and biocurators which provide gene- and disease- specifications to the American College of Medical Genetics & Genomics and Association for Molecular Pathology's (ACMG/AMP) variation classification guidelines. With the goal of classifying the clinical significance of GAA variants in Pompe disease (Glycogen storage disease, type II), the ClinGen Lysosomal Diseases (LD) VCEP has specified the ACMG/AMP criteria for GAA.

Development of a clinically validated functional assay to assess pathogenicity of novel variants in patients with Pompe disease identified newborn screening.

The addition of Pompe disease (Glycogen Storage Disease Type II) to the Recommended Uniform Screening Panel in the United States has led to an increase in the number of variants of uncertain significance (VUS) and novel variants identified in the gene. This presents a diagnostic challenge, especially in the setting of late-onset Pompe disease when symptoms are rarely apparent at birth. There is an unmet need for validated functional studies to aid in classification of variants.

Engineering lipases for temperature adaptation: Structure function correlation.

Bacillus lipases are industrially attractive enzymes due to their broad substrate specificity and optimum alkaline pH. However, narrow temperature range of action and low thermostability restrain their optimal use and thus, necessitate attention. Several laboratories are engaged in protein engineering of Bacillus lipases to generate variants with improved attributes for decades using techniques such as directed evolution or rational design.

Geographic Plasmodium falciparum sarcoplasmic reticulum Ca2+ ATPase (PfSERCA) genotype diversity in India.

Plasmodium falciparum sarcoplasmic reticulum Ca ATPase (PfSERCA) is sarcoplasmic reticulum membrane bound transporter to regulate cytosol Ca ions. Ca act as secondary messenger and play important role in differentiation of parasite during its life cycle. Present study is epidemiological surveillance of PfSERCA (Pf3D7_0106300) gene fragment harboring 263, 402, 431 codon to look for its single nucleotide polymorphism which is well documented to be associated with Artemisinin tolerance.

Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicated Plasmodium falciparum malaria cases along international border of north east India.

PfMDR1 single nucleotide polymorphisms (SNP) are good correlate markers for antimalarial drug resistance worldwide. Present study is a comprehensive view of screening of PfMDR1 polymorphism to antimalarials practiced with geography and time. Study sites Mizoram, Tripura, Meghalaya chosen are at multivariate drug pressure due to cross border migration and transmission.

Point mutation Gln121-Arg increased temperature optima of Bacillus lipase (1.4 subfamily) by fifteen degrees.

Small molecular weight Bacillus lipases are industrially attractive because of its alkaline optimum pH, broad substrate specificity and production in high yield by overexpression both in Escherichia coli and Bacillus subtilis. Its major limitation of being mesophilic in nature is constantly targeted by laboratory evolution studies. Herein metagenomically isolated Bacillus LipJ was randomly evolved by error prone PCR and library of variants were screened for enhanced thermostability.

Point Mutation Ile137-Met Near Surface Conferred Psychrophilic Behaviour and Improved Catalytic Efficiency to Bacillus Lipase of 1.4 Subfamily.

Bacillus lipolytic enzymes of subfamily 1.4 are industrially attractive because of its alkaline optimum pH and broad substrate specificity. The activity and stability of these enzymes for a limited temperature range (30-50 °C) need attention for its industrial application.

Disruption of N terminus long range non covalent interactions shifted temp.opt 25°C to cold: Evolution of point mutant Bacillus lipase by error prone PCR.

Cold adapted enzymes have applications in detergent, textile, food, bioremediation and biotechnology processes. Bacillus lipases are 'generally recognized as safe' (GRAS) and hence are industrially attractive. Bacillus lipase of 1.