Cystic fibrosis in Pakistan: population harbouring rare variants non-responsive to CFTR modulators and the dilemma of poor health facilities.

Background: Pathogenic mutations in the CFTR gene disrupt the normal function of the chloride ion channel CFTR protein, resulting in Cystic Fibrosis (C.F.).

Genetic Variations on Chromosome 6p21 Are Associated with Asthma Risk and Disease Severity: A Case-Control Study from Pakistan.

Background: Genetic factors play a role in asthma severity. However, low- and middle-income countries have minimal contribution to genomic asthma research. The current study investigates the influence of an important genetic asthma region (6p21) on severe asthma in a cohort of asthmatics in Pakistan.

Ethnogenetic analysis reveals the Bronze Age genetic affiliation of Yashkuns with West Eurasians.

Focusing on the Yashkun population of Gilgit-Baltistan, an administrative territory in northern Pakistan, our study investigated mtDNA haplotypes as indicators of ancient gene flow and genetic diversity. Genomic DNA was extracted and evaluated for quality using agarose gel electrophoresis. The complete control region of mtDNA (nt 16024-576) was amplified via PCR, and sequencing was performed using the Big Dye Terminator Kit on an Applied Biosystems Genetic Analyzer.

Role of Vascular Endothelial Growth Factor as a Potential Biomarker in Congenital Heart Defects: A Systematic Review.

Background: Several studies have investigated the role of vascular endothelial growth factor (VEGF) variants, serum levels, and correlations with other extrinsic factors in congenital heart defects (CHDs); however, the findings need confirmation. The present systematic review evaluates the association between CHDs and genetic polymorphisms and serum expressions.

Methods: Relevant literature was searched through electronic databases using keywords and MeSH terms.

Stepping towards pollen DNA metabarcoding: A breakthrough in forensic sciences.

This review is engaged in determining the capability of plant pollen as a significant source of evidence for the linkage between suspects and crime location in forensic sciences. Research and review articles were collected from Google Scholar, the Web of Science, and PubMed. Articles were searched using specific keywords such as "Forensic Palynology," "Pollen metabarcoding," "Plant forensics," and "Pollen" AND "criminal investigation.

Genetic Risk Score Constructed from Polymorphisms in the VEGFA, TBX5, and SMAD7 Genes Provides Novel Insights into the Molecular Mechanisms of the Tetralogy of Fallot and Ventricular Septal Defect (Case-Control Study from the Pakistani Population).

Congenital heart defects are common and complex birth-defect malformations in developed and developing countries. It is a multifactorial disease that involves the interaction of either gene-gene or gene-environment. This comparative study was the first report on the genotypic-phenotypic correlation in the Pakistani population.

Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population.

Background: Globally, congenital heart defect (CHD) is the most common congenital malformation, responsible for higher morbidity and mortality in the pediatric population. It is a complex multifactorial disease influenced by gene-environment and gene-gene interactions. The current study was the first attempt to study these polymorphisms in common clinical phenotypes of CHD in Pakistan and the association between maternal hypertension and diabetes with single nucleotide polymorphisms (SNPs) in children.

Single Nucleotide Polymorphisms Of Transforming Growth Factor-Β1 Gene As Potential Asthma Susceptible Variants In Punjabi Population Of Pakistan.

Background: Candidate gene approach based on case-control model is a valuable strategy to determined disease related genetic variants. Two single nucleotide polymorphisms rs1800469 and rs2241715 in TGF β1gene have been reported to affect the asthmatic status in different populations. The main focus of this research was to find any relationship between these SNPs and asthma in Pakistani population.

Prevention programmes and prenatal diagnosis for beta thalassemia in Pakistan: A narrative review.

Beta thalassemia in Pakistan is a serious health concern with an estimated 5-8% carrier frequency and birth of 5000 major children every year in the country. The treatment of beta thalassemia major patients poses a great economic burden; hence, the ideal approach towards this disease should encompass effective prevention services. At present only one government funded project "Punjab Thalassemia Prevention Programme" existed in Punjab province, and providing free of cost services for beta thalassemia screening and prenatal diagnosis.

Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression.

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis.

Background: The gene NKX2-5 is a key transcription factor that plays an essential role in normal cardiac development. Although some recent studies have studied the role of polymorphisms in the NKX2-5 gene in congenital heart diseases (CHDs), the results were not consistent and remained uncertain. Therefore, we conduct a review of literature and investigate the association of genetic polymorphisms with CHDs.

Discovery and Protein Modeling Studies of Novel Compound Mutations Causing Resistance to Multiple Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.

Objective: BCR-ABL fusion oncogene is the hallmark of chronic myeloid leukemia (CML), causing genomic instability which leads to accumulation of mutations in BCR-ABL as well as other genes. BCR-ABL mutations are the cause of tyrosine kinase inhibitors (TKIs) resistance in CML. Recently, compound BCR-ABL mutations have been reported to resist all FDA approved TKIs.

Familial DNA analysis and criminal investigation: Usage, downsides and privacy concerns.

Since the discovery of Deoxyribonucleic acid (DNA) capability in forensic investigation, it has been an important part of the criminal justice system. In most criminal cases DNA profile originating from evidence sample collected from the crime scene is compared with the DNA profile from the reference sample. However, when a reference sample is not available for comparison, familial DNA analysis can provide important investigation leads in a criminal investigation process by identifying an individual.

Major histocompatibility complex class II polymorphic variants are associated with asthma predisposition in the Punjabi population of Lahore, Pakistan.

Introduction: Various genome wide association studies have manifested that Major Histocompatibility Complex (MHC) region on chromosome 6p21 houses many potential candidate genes for asthma.

Objective: This Case-Control association study was planned to determine the association of 10 Single Nucleotide Polymorphisms (SNPs), residing within and around MHC genes' region on chromosome 6p21, with Asthma in Punjabi population of Lahore, Pakistan.

Methods: A total of 161 subjects, 61 physician-diagnosed asthma patients and 100 age-matched healthy controls, were recruited from Lahore, a city in Punjab.

Detection of Exon 12 and 14 Mutations in Janus Kinase 2 Gene Including a Novel Mutant in V617F Negative Polycythemia Vera Patients from Pakistan.

The most frequently reported genetic aberration among polycythemia vera (PV) patients is a gain of function mutation V617F in exon 14 of Janus kinase 2 (JAK2) gene. However in many investigations, V617F negative PV patients have been reported to harbor mutations in JAK 2 exon 12. We investigated 24 patients with PV (diagnosed following 2016 WHO guidelines) to detect V617F mutation through allele specific PCR.

Role of Molecular Biology in Cancer Treatment: A Review Article.

Background: Cancer is a genetic disease and mainly arises due to a number of reasons include activation of onco-genes, malfunction of tumor suppressor genes or mutagenesis due to external factors.

Methods: This article was written from the data collected from PubMed, Nature, Science Direct, Springer and Elsevier groups of journals.

Results: Oncogenes are deregulated form of normal proto-oncogenes required for cell division, differentiation and regulation.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

BCR-ABL kinase domain (K) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients.

rs12603332 is associated with male asthma patients specifically in urban areas of Lahore, Pakistan.

Objective: rs12603332, an important regulatory site variant, is known to alter the regulatory motif E2A that is involved in the maturation of B-lymphocytes. The study was designed to check whether different environmental exposures alter its risk allele association with asthma or not.

Methods: 200 Physician-diagnosed asthma patients and 108 healthy individuals were enrolled from hospitals of Lahore.

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan.

Objective: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan.

High frequency and poor prognosis of late childhood BCR-ABL-positive and MLL-AF4-positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan.

Background: Fusion oncogenes (FOs) resulting from chromosomal abnormalities have an important role in leukemogenesis in pediatric B cell acute lymphoblastic leukemia (ALL). The most common FOs are BCR-ABL, MLL-AF4, ETV6-RUNX1, and TCF3-PBX1, all of which have important prognostic and drug selection implications. Moreover, frequencies of FOs have ethnic variations.

Sequence variants on 17q21 are associated with the susceptibility of asthma in the population of Lahore, Pakistan.

Objective: Single nucleotide polymorphisms (SNPs) on 17q21 are known to be associated with asthma disease in multiple populations. This study was designed to know whether this region is associated with asthma in Lahore region population or not.

Methods: A total of 200 asthma patients and 100 healthy controls were enrolled from different hospitals of Lahore, Pakistan.

Allele frequency distribution of CYP2C19*2 allelic variants associated with clopidogrel resistance in cardiac patients.

Drug resistance is a phenomenon that has become a critical issue in medical practice. Such is the case in the response to clopidogrel treatment, which is variable inter-individually and inter-ethnically due to genetic polymorphisms in the cytochrome P40 (CYP) gene. Clopidogrel is an anti-platelet agent administered to cardiac patients in the form of a prodrug, which is further metabolized into an active form by CYP enzymes.

PEG-interferon conjugates: effects of length and structure of linker.

Di-branched (Y-shaped) polyethylene glycols (PEGs) are considered more effective than linear molecules to enhance the efficacy of the conjugated drug. In the present study interferon α-2a was conjugated with three different 40 KDa di-branched PEGs. The results of this study show that length and/or the structure of linker between PEG and the protein is also involved in the synthesis, in vitro biological activity and stability of the conjugate.

Five most common prognostically important fusion oncogenes are detected in the majority of Pakistani pediatric acute lymphoblastic leukemia patients and are strongly associated with disease biology and treatment outcome.

Background And Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome.

Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome.