Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy.

Background: Adequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2.

Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5-2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition.

Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability.

Intellectual disability (ID) is a condition of significant limitation of cognitive functioning and adaptive behavior, with 50% of etiology attributed to genetic predisposition. We recruited two consanguineous Pakistani families manifesting severe ID and developmental delay. The probands were subjected to whole exome sequencing (WES) and variants were further prioritized based on population frequency, predicted pathogenicity and functional relevance.

9p21 Locus Polymorphism Is A Strong Predictor of Metabolic Syndrome and Cardiometabolic Risk Phenotypes Regardless of Coronary Heart Disease.

The world population is genetically predisposed to metabolic syndrome (MetS) and its components, also known as cardiometabolic risk phenotypes, which can cause severe health complications including coronary heart disease (CHD). Genetic variants in the 9p21 locus have been associated with CHD in a number of populations including Pakistan. However, the role of the 9p21 locus in MetS and cardiometabolic risk phenotypes (such as obesity, hypertension, hyperglycemia, and dyslipidemia) in populations with CHD or no established CHD has not been explored.

Demographic and Clinical Determinants of Tuberculosis and TB Recurrence: A Double-Edged Retrospective Study from Pakistan.

Objective: TB recurrence is the second episode of TB after initial treatment bringing about an additional 7% load in TB burden intensified by 17.7% of multidrug-resistant recurrent cases. It is necessary to curb recurrence so that attempts to deal with active disease can be made more effective.

Study of HLA class II loci reveals DQB1*03:03:02 as a risk factor for asthma in a Pakistani population.

Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as DRB1 and DQB1 are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population.

A Novel Missense Mutation in Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani Family.

Autosomal-recessive cerebellar ataxias (ARCAs) are heterogeneous rare disorders mainly affecting the cerebellum and manifest as movement disorders in children and young adults. To date, ARCA causing mutations have been identified in nearly 100 genes; however, they account for less than 50% of all cases. We studied a multiplex, consanguineous Pakistani family presenting with a slowly progressive gait ataxia, body imbalance, and dysarthria.

SNP-Based Genome-Wide Association Mapping of Pollen Viability Under Heat Stress in Tropical L. Inbred Lines.

Global environmental changes with more extreme episodes of heat waves are major threats to agricultural productivity. Heat stress in spring affects the reproductive stage of maize, resulting in tassel blast, pollen abortion, poor pollination, reduced seed set, barren ears and ultimately yield loss. As an aneamophelous crop, maize has a propensity for pollen abortion under heat stress conditions.

Genetic association study of ERBB4 SNP rs1351592 with polycystic ovary syndrome in Pakistani population.

Polycystic ovary syndrome (PCOS) is an oligogenic condition characterised by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Previously, European and Han Chinese populations identified different susceptibility loci, of which ERBB4 (rs1351592) was strongly associated with PCOS. Our study aimed to investigate the association of ERBB4 Single Nucleotide Polymorphism (SNP), rs1351592 with PCOS in Pakistani women of Hazara region.

Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide.

Because transethnic analysis may facilitate prioritization of causal genetic variants, we performed a genomewide association study (GWAS) of psoriasis in South Asians (SAS), consisting of 2,590 cases and 1,720 controls. Comparison with our existing European-origin (EUR) GWAS showed that effect sizes of known psoriasis signals were highly correlated in SAS and EUR (Spearman ρ = 0.78; < 2 × 10).

Phytochemistry, antioxidant and antibacterial activities of fruit extracts of Myrsine africana L.

Myrsine africana L. a commonly consumed medicinal plant grows in forest of mountains region located at North East of Pakistan. In current study, the fruit extracts were chemically characterized and their bioactivities were determined.

Correlation of C-reactive protein levels, gene polymorphism and platelets count in Dengue infection.

Objective: To determine the correlation of polymorphism in C-reactive protein gene with variation in serum levels in dengue patients.

Methods: The cross-sectional study was conducted at Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan, from October 2017 to October 2018, and comprised blood samples from dengue patients which were used to measure the serum levels of C-reactive protein. Deoxyribonucleic acid extraction followed by tetra amplification-refractory mutation system polymerase chain reaction was used to analyse the genotype variation T>G for single nucleotide polymorphism rs199953854 using allele-specific primers.

Isolation of Oxyberberine and -Sitosterol from Royle Root Bark Extract and Cytotoxicity against Liver and Lung Cancer Cell Lines.

Royle has been traditionally used to cure rheumatism, eye and ear diseases, malarial fever, diabetes, stomach disorders, and skin diseases. There is a least amount of data available on cytotoxic capacity of from Pakistani origin, so on this basis, the present study was aimed to screen root bark extracts for cytotoxicity against cancer cell lines and isolation of chemical constituents from the most cytotoxic extract. Initial screening of extracts was performed on HepG2 cells at 100 g/mL for 72 hours of treatment by using an MTT assay.

Sequence variants in three genes underlying leukodystrophy in Pakistani families.

Leukodystrophies (LDs) are a heterogeneous group of rare and progressive genetic diseases that affect brain, spinal cord, and often the peripheral nerves. They are characterized by abnormal development or destruction of the myelin sheath of the brain. This study was aimed to search for the causative variants in three unrelated consanguineous families presented with LD.

Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia.

Bakground: Hereditary Spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of degenerative disorders characterized by progressive spasticity and weakness of the lower limbs. This study aimed to identify causative gene variants in two unrelated consanguineous Pakistani families presented with 2 different forms of HSP.

Methods: Whole exome sequencing (WES) was performed in the two families and variants were validated by Sanger sequencing and segregation analysis.

Body Mass Index versus Other Adiposity Traits: Best Predictor of Cardiometabolic Risk.

Background: A number of anthropometric indices have been used in different world populations as markers to estimate obesity and its related health risks. The present study is large population based study dealing with five anthropometric obesity scales; Body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), basal adiposity index (BAI), and Visceral adiposity index (VAI) to identify common adiposity trait(s) that best predict obesity and associated health complication(s).

Methods: A total of 4000 subjects including 1000 in each category of BMI from four provinces (Punjab, Sindh, Kahyber pakhtoonkha and Balochistan) of Pakistan from 2012-2017 were collected.

Contributions of Interactions Between Lifestyle and Genetics on Coronary Artery Disease Risk.

Purpose Of The Review: To summarize current knowledge on interactions between genetic variants and lifestyle factors (G×L) associated with the development of coronary artery disease (CAD) and prioritize future research.

Recent Findings: Genetic risk and combined lifestyle factors and behaviors have a log-additive effect on the risk of developing CAD. First, we describe genetic and lifestyle factors associated with CAD and then focus on G×L interactions.

Significant association of DRD2 enhancer variant rs12364283 with heroin addiction in a Pakistani population.

The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed.

Development of amplified fragment length polymorphism (AFLP) markers for the identification of Cholistani cattle.

The identification issue of livestock can be resolved by using molecular identification tools that are acceptable to preserve and maintain pure breeds worldwide. The application of a molecular identification methodology is more important for developing nations, e.g.

Association of CACNA1C with bipolar disorder among the Pakistani population.

Many single nucleotide polymorphisms (SNPs) have been identified for Bipolar disorder (BD), but association between SNPs and BD can vary depending on the population tested. SNPs rs10994336 and rs9804190 in ANK3 and rs1006737 in CACNA1C have emerged as the most highly replicated SNPs significantly associated with BD. The aim of the present study was to assess the association of these SNPs with BD in the Pakistani population, which has never before been examined.

Single nucleotide polymorphisms in asthma candidate genes , and in Pakistani asthmatics a case control study.

Background: Genetic variations in different loci and genes are important in asthma pathogenesis. There is much importance of various immunological pathways in the IgE secretion regulation. Alterations in any main part of these pathways can increase the risk of asthma development.

Screening of cardiometabolic risks clustering in young Pakistani adults classified by anthropometric traits.

Objective: To estimate frequencies of metabolic risk phenotypes and their associations in body mass index and waist circumference-based obesity categories.

Methods: The cross-sectional study was conducted at Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan, from August 2014 to March 2016. Anthropometric and clinical data of young adults was collected.