Understanding the anti-Mughal Struggle of Khushal Khan Khattak

Khushal Khan Khattak, a seventeenth century Pakhtun writer, poet and swordsman, and his forefathers had served the Mughal for a long time. However, his fortune took a sudden twist when Mughal Emperor Aurangzeb imprisoned him in 1664, and kept him in solitary confinement at Ranthambore fort. After his release from prison, Khushal Khan was a different person. He remained no more a loyal Mughal official afterwards. Although, Aurangzeb Alamgir and a number of Mughal governors of Kabul tempted him several time to accept a position in the frontier areas but he out-rightly declined. This transformation is clearly visible in his poetry. He took up arms against the Mughals in 1673 and declared a war against them despite the fact that some of his family members even his son had sided with the Mughals. He continued his anti-Mughal struggle till his death in 1689. Some of the critics look at the antiMughal role of Khushal Khan with suspicion and have raised a few queries in this connection. This study looks into the circumstances that saw transformation in his outlook towards the Mughals. Then it explores, whether it was a personal vendetta or the start of a collective anti-Mughal Pakhtun struggle. The article looks into various dimensions, nature and direction of his struggle. This research paper is an attempt to evaluate objectively as to why and how Khushal Khan joined the anti-Mughal camp in the borderland area. Some more related questions are also discussed in details in this article.

Gene Identification in Mendelian Disorders Using Whole Exome Sequencing

Genetic disorders are a major cause of disabling conditions in regions of the world with high rates of consanguinity. Pakistan has a tradition of consanguineous marriages and therefore a high prevalence of Mendelian disorders. Charcot-Marie-Tooth syndrome and autosomal recessive spastic ataxia of Charlevoix-Saguenay affect peripheral nerves leading to severe foot deformity. Cerebral palsy, ataxia telangiectasia and hereditary multiple exostoses are some examples of the disorders that renders a person incapable of spending a normal life style. Such abnormalities may incapacitate the socioeconomic development of a country by putting forth major burden with respect to providing health care facilities. Importantly, ensuring the normality of a fetus will likely decrease the number of pregnancies a couple may have thereby decreasing the burden on society and family. Recent advancements in genomics enable genetic screening of large cohorts. Next generation sequencing technologies are used to identify genes, gene variants and variable expression associated with specific phenotypes. Exonic regions are known to contain most of the variants responsible for Mendelian disorders. Traditional approaches like linkage analysis and Sanger sequencing of candidate genes are costly or time consuming and a large samples size is required for this purpose. In this study ten inbred families from Pakistan were investigated using whole exome sequencing as a diagnostic and mutation identifying tool. Variants form whole exome sequencing were prioritized based on their functional relevance, disease association, pedigree information, inheritance pattern and pathogenicity scores using bioinformatics software. All the variants were validated through Sanger sequencing to rule out errors. Five novel mutations and two previously reported mutations were identified in this study. These variants were also evaluated for their functional impact using various bioinformatics tools. The findings in this study will help in understanding the disease mechanism and related pathways as well as annotating various entities of genome. The incidence of these disorders in Pakistan can be reduced through efficient carrier screening, genetic counseling, prenatal diagnosis and improved therapeutic approaches.