ABSTRACT
Hepatitis C virus [HCV] stands as a health problem experienced across the globe leading to chronic or acute liver disease such as cirrhosis, hepatocellular carcinoma and various others. It is a complex disease with extensive genetic heterogeneity with little known about the interactions of complex intra- and intercellular processes. The evolving tools in the application of network science to identify diseases have paved a way for the study of complex diseases at system level. This study focuses on identifying the significant proteins and the biological regulatory pathways involved in hepatitis C virus and performing topological analysis of the PPIs derived by the proteins encoded by the susceptible genes in order to look for the molecular connectivity between these pathways
ABSTRACT
To characterize the disease causing mutation in a large consanguineous Pakistani family with severe Mal de Meleda [MDM] or keratosis palmoplantaris transgrediens, a rare autosomal recessive skin disorder. Single nucleotide polymorphism [SNPs] genotyping was performed using the GeneChip Mapping 250K array [Affymetrix]. Homozygosity mapping and sorting of genomic regions were performed with dedicated software called AutoSNPa. Selected regions were further investigated by genotyping with microsatellite markers derived from known and novel polymorphic repeats. Two-point LOD score calculation was performed by using the MLINK of Fastlink computer package. All three coding exons of ARS [component B] gene were amplified by PCR and sequenced. Sequencing of all the coding exons of ARS [component B] gene in the affected individuals revealed a recurrent missense mutation in exon 3 at base pair 256 from Guanine to Alanine [256G>A] and as a result the amino acid Glycine is replaced by Arginine at position 86 [G86R]. This finding will facilitate control of affected MDM births in the Pakistani families