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Hussain R.,BUITEMS | Hussain R.,Sardar Bahadur Khan Womens University | Daud S.,Center for Applied Molecular Biology | Daud S.,Institute of Biochemistry and Biotechnology | And 6 more authors.
Molecular Biology Reports | Year: 2012

Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM-000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A?G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family. © Springer Science+Business Media B.V. 2011.

Chen X.,Nanjing Agricultural University | Chen X.,Louisiana State University Health Sciences Center | Gu Y.,Nanjing Agricultural University | Gu Y.,Louisiana State University Health Sciences Center | And 8 more authors.
PLoS ONE | Year: 2014

Maduramicin, a polyether ionophore antibiotic derived from the bacterium Actinomadura yumaensis, is currently used as a feed additive against coccidiosis in poultry worldwide. It has been clinically observed that maduramicin can cause skeletal muscle and heart cell damage, resulting in skeletal muscle degeneration, heart failure, and even death in animals and humans, if improperly used. However, the mechanism of its toxic action in myoblasts is not well understood. Using mouse myoblasts (C2C12) and human rhabdomyosarcoma (RD and Rh30) cells as an experimental model for myoblasts, here we found that maduramicin inhibited cell proliferation and induced cell death in a concentration-dependent manner. Further studies revealed that maduramicin induced accumulation of the cells at G0/G1 phase of the cell cycle, and induced apoptosis in the cells. Concurrently, maduramicin downregulated protein expression of cyclin D1, cyclin-dependent kinases (CDK4 and CDK6), and CDC25A, and upregulated expression of the CDK inhibitors (p21Cip1 and p27 Kip1), resulting in decreased phosphorylation of Rb. Maduramicin also induced expression of BAK, BAD, DR4, TRADD and TRAIL, leading to activation of caspases 8, 9 and 3 as well as cleavage of poly ADP ribose polymerase (PARP). Taken together, our results suggest that maduramicin executes its toxicity in myoblasts at least by inhibiting cell proliferation and inducing apoptotic cell death.Copyright: © 2014.

Tahir M.S.,Institute of Biochemistry and Biotechnology | Hussain T.,The University of Lahore | Babar M.E.,The University of Lahore | Nadeem A.,Institute of Biochemistry and Biotechnology | And 4 more authors.
Journal of Animal and Plant Sciences | Year: 2015

A molecular genetics tool comprised of a panel of 15 microsatellite markers was developed and used to investigate parentage and breed characterization of two most kept breeds of dogs including German shepherd and Labrador retriever in Pakistan. Blood samples of 20 dog families (10 from each breed) were collected from Army dog Breeding Training Center and School, Rawalpindi, Pakistan and Kennel Club of Pakistan. Genomic DNA was extracted by standard inorganic protocol. Microsatellite markers with high Polymorphism Information Content (PIC) and He (Hetrozygosity) values were selected and optimized into four multiplexes. Amplification reactions were followed by genotyping in 7% non-denaturing polyacrylamide gel electrophoresis (PAGE). Parentage analysis of 20 families using this panel of microsatellite markers was 100% successful. Average values of Polymorphism Information Content (PIC), Heterozygosity (He) and Combined Power of Exclusion (CPE) combined for both of the breeds were found to be 0.724, 0.6345 and 0.9998 respectively. Moreover, deviation from Hardy-Weinberg equilibrium equation was observed moderately for both dog breeds. Allelic frequencies for majority of the microsatellite markers between both dog breeds were clearly distinct. This study demonstrated the panel of 15 microsatellite markers could effectively validate parentage and breed characterization in dogs. © 2015, Pakistan Agricultural Scientists Forum. All rights reserved.

Ahmad A.,BUITEMS | Ahmad A.,Institute of Biochemistry and Biotechnology | Daud S.,University of Punjab | Kakar N.,BUITEMS | And 9 more authors.
Molecular Vision | Year: 2011

Purpose: To determine the cause of Leber congenital amaurosis (LCA) and developmental cataracts in a consanguineous Pakistani family. Methods: The diagnosis was established in all affected individuals of a Pakistani LCA family by medical history, funduscopy, and standard ERG. We performed genome-wide linkage analysis for mapping the disease locus in this family. Results: Congenitally severely reduced visual acuity and nystagmus were reported for all patients who, in the later phase of the disease, also developed cataracts. LCA in the family cosegregated with homozygosity for a single nucleotide polymorphism (SNP) haplotype on chromosome 6p14.1. The respective candidate region contained Leber congenital amaurosis 5 (LCA5), a gene previously reported to underlie LCA. We subsequently identified a novel truncating mutation in exon 4 of LCA5, c.642delC, in homozygous state in all affected persons of the family. Conclusions: We report a novel LCA5 mutation causing LCA in a Pakistani family. Developmental cataracts were present in two of the four patients, raising the possibility that LCA5 mutations may predispose to this additional ocular pathology. © 2011 Molecular Vision.

Afridi S.Q.,Quality Operations Laboratory | Ali M.M.,Institute of Biochemistry and Biotechnology | Awan F.,UVAS | Zahid M.N.,Quality Operations Laboratory | And 3 more authors.
Virology Journal | Year: 2014

Background: Hepatitis C virus (HCV) is highly infectious pathogen which is responsible for causing Hepatitis around 200 million individuals worldwide. In Pakistan, 4.7% of HCV prevalence has been reported and HCV genotype 3a has been found to be the major source of infection in Pakistan but still there is lack of information on distribution of HCV genotypes and viral load in various geographical regions of Pakistan. Therefore, current study was designed to determine distribution of HCV genotypes as well viral load in different areas of Punjab province of Pakistan. Findings. A total of 995 serum samples were taken from those individuals in which antibodies against HCV were detected through ELISA, from different regions of Punjab i.e. Lahore 317(31.85%), Faisalabad 70(7.03%), Gujranwala 129(12.96%), Gujrat 106(10.65%), Sialkot 94(9.44%), Sargodha 60(6.03%), Mandibaha-ud-din 135(13.56%), Jhang 86(8.64%). Qualitative PCR was performed to determine viral load and genotyping was performed using Nested PCR. Chi-square test was used to determine the age and sex-wise prevalence of HCV. Out of 995 samples, 888 samples were found positive for HCV RNA. In all regions, genotype 3a showed highest prevalence (82.81%) followed by genotype 1 (3.41%), mixed genotypes (2.41%), genotype 2 (0.50%), genotype 5 (0.1%) and unclassified genotypes (10.75%). Viral load in 29.5% patients infected with genotype 3a was less than 600,000 IU/mL, while it was between 600,000-800,000 IU/mL in 27.9% patients and 25.22% patients had more than 800,000 IU/mL viral load. Conclusion: HCV genotype 3a is the most prevalent genotype in various regions of Punjab. Viral load of HCV patients in these different regions of Punjab are reported for the first time. Moreover, based upon these results the Patients having viral load below 800,000 IU/mL would be expected to show better response of anti-HCV therapy. © 2014 Afridi et al.; licensee BioMed Central Ltd.

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