Gene mapping in syndactyly families

Non-syndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and/or toes. It has a prevalence of 3 per 10,000 births. The malformation can be unilateral or bilateral, and the fusion within the web may be cutaneous or bony. Phenotypic variability exists not only between affected individuals, but also within individuals. Nine different types have been described majority of which show autosomal dominant mode of inheritance, except Cenani-Lenz type (type VII) and Malik-Percin syndactyly (type IX) which segregate as autosomal recessive entities. Syndactyly shows failure to achieve a normal limb development, more precisely, the malformation affects the digits number, identity and separation in the last developmental cascades. In this thesis I report on the clinical and molecular data as well as gene localizations in three large Pakistani families with non-syndromic syndactylies. · I have categorized these families according to the existing syndactyly classification. · I have proposed a clinical protocol which helps to use the existing systematics of syndactyly, and on the other hand simplifies the clinical typing of this malformation. · For the first time I report on a family with a novel autosomal recessive hand/foot malformation with mesoaxial synostotic syndactyly (Family 1). In order to classify this type, I have extended the existing syndactyly systematics and have proposed a new name for this novel syndactyly: mesoaxial synostotic syndactyly with phalangeal reduction (MSSD); type IX syndactyly, Malik-Percin type. This term was introduced into the international literature. Through a genome-wide study with highly polymorphic microsatellite markers and linkage analysis, I have localized this unique autosomal recessive syndactyly phenotype on chromosome 17p13.3 with a disease interval of ~5 cM. · By my own experience of phenotyping limb defects in different families and by reviewing the international literature I propose that type I syndactyly has at least four subtypes. I have established that zygodactyly in Family 2, the most common subtype, has a locus on chromosome 3p21.31 with a critical interval of ~0.38 Mb. Additionally, I provide molecular evidence of further genetic heterogeneity within zygodactyly. Considering the high prevalence of zygodactyly in all populations I expect, that diverse loci are responsible for the phenotype and therefore I expect more loci. · Since HOXD13 gene has been excluded in Family 3, therefore, I have good evidence that syndactyly type II is genetically heterogeneous. A genome-wide search has depicted that the phenotype in this family is mapped on chromosome 14q12 and might have a modifier locus on chromosome 2q34-q36. The discovery of three novel loci for syndactylies will significantly help in the clinical and genetic delineation of this complex limb malformation. It will be of tremendous help to the families with limb malformations seeking genetic advice. The ultimate elucidation of the underlying genes might increase our understanding of limb development, especially in the context of getting insight into the developmental cascades of digit number, identity and separation

Reforming education in Pakistan – tracing global links

This paper is about tracing global links in national education reforms in Pakistan. The paper tries to describe globalization and its general effects on national policies. It particularly highlights the effects of globalization on education reforms, which are: competitiveness-driven, finance-driven and equity-driven. In light of these global education reform patterns the paper explores the major educational reforms being pursued in Pakistan since 1990s. The paper argues that globalization has seriously challenged the national reform policies, which are now becoming more and more globally driven. Rather than out rightly rejecting all global policies, engaging critically with them is the stance of the authors

Intuitionistic Fuzzy Broad Learning System: Enhancing Robustness Against Noise and Outliers

In the realm of data classification, broad learning system (BLS) has proven to be a potent tool that utilizes a layer-by-layer feed-forward neural network. It consists of feature learning and enhancement segments, working together to extract intricate features from input data. The traditional BLS treats all samples as equally significant, which makes it less robust and less effective for real-world datasets with noises and outliers. To address this issue, we propose the fuzzy BLS (F-BLS) model, which assigns a fuzzy membership value to each training point to reduce the influence of noises and outliers. In assigning the membership value, the F-BLS model solely considers the distance from samples to the class center in the original feature space without incorporating the extent of non-belongingness to a class. We further propose a novel BLS based on intuitionistic fuzzy theory (IF-BLS). The proposed IF-BLS utilizes intuitionistic fuzzy numbers based on fuzzy membership and non-membership values to assign scores to training points in the high-dimensional feature space by using a kernel function. We evaluate the performance of proposed F-BLS and IF-BLS models on 44 UCI benchmark datasets across diverse domains. Furthermore, Gaussian noise is added to some UCI datasets to assess the robustness of the proposed F-BLS and IF-BLS models. Experimental results demonstrate superior generalization performance of the proposed F-BLS and IF-BLS models compared to baseline models, both with and without Gaussian noise. Additionally, we implement the proposed F-BLS and IF-BLS models on the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset, and promising results showcase the models effectiveness in real-world applications. The proposed methods offer a promising solution to enhance the BLS frameworks ability to handle noise and outliers

The Secular Side of Islam: a Case Study of Tariq Ali’s Islam Quintet

The present study discusses the secular side of Islamic civilization in Tariq Ali’s Islam Quintet. Against the misrepresentation of Islam in the western discourse, Ali’s Islam Quintet depicts the past history of Muslims that highlights the secular, tolerant, pluralistic and intellectual side of the Islamic civilization. The study is qualitative in nature. The technique of content analysis was used to analyse the texts of three novels – Shadows of the pomegranate tree, The Book of Saladin, A Sultan in Palermo – of Islam Quintet to argue that the author deconstructs the western notions about Islam and retells the history from other’s perspective. The analysis of the Shadows of the Pomegranate Tree demonstrates that the Muslims of Banu Hudayl lived secular lives and their actions and decisions were determined by material and economic motives. Furthermore, the study highlights the intellectual, rational, tolerant and secular side of some significant historical and fictional characters in “the Book of Saladin” and “a Sultan in Palermo”. Keywords: Christian Europe, Islamic civilization, Islam Quintet, Orientalism, Secular aspec

Gene mapping in syndactyly families

Non-syndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and/or toes. It has a prevalence of 3 per 10,000 births. The malformation can be unilateral or bilateral, and the fusion within the web may be cutaneous or bony. Phenotypic variability exists not only between affected individuals, but also within individuals. Nine different types have been described majority of which show autosomal dominant mode of inheritance, except Cenani-Lenz type (type VII) and Malik-Percin syndactyly (type IX) which segregate as autosomal recessive entities. Syndactyly shows failure to achieve a normal limb development, more precisely, the malformation affects the digits number, identity and separation in the last developmental cascades. In this thesis I report on the clinical and molecular data as well as gene localizations in three large Pakistani families with non-syndromic syndactylies. · I have categorized these families according to the existing syndactyly classification. · I have proposed a clinical protocol which helps to use the existing systematics of syndactyly, and on the other hand simplifies the clinical typing of this malformation. · For the first time I report on a family with a novel autosomal recessive hand/foot malformation with mesoaxial synostotic syndactyly (Family 1). In order to classify this type, I have extended the existing syndactyly systematics and have proposed a new name for this novel syndactyly: mesoaxial synostotic syndactyly with phalangeal reduction (MSSD); type IX syndactyly, Malik-Percin type. This term was introduced into the international literature. Through a genome-wide study with highly polymorphic microsatellite markers and linkage analysis, I have localized this unique autosomal recessive syndactyly phenotype on chromosome 17p13.3 with a disease interval of ~5 cM. · By my own experience of phenotyping limb defects in different families and by reviewing the international literature I propose that type I syndactyly has at least four subtypes. I have established that zygodactyly in Family 2, the most common subtype, has a locus on chromosome 3p21.31 with a critical interval of ~0.38 Mb. Additionally, I provide molecular evidence of further genetic heterogeneity within zygodactyly. Considering the high prevalence of zygodactyly in all populations I expect, that diverse loci are responsible for the phenotype and therefore I expect more loci. · Since HOXD13 gene has been excluded in Family 3, therefore, I have good evidence that syndactyly type II is genetically heterogeneous. A genome-wide search has depicted that the phenotype in this family is mapped on chromosome 14q12 and might have a modifier locus on chromosome 2q34-q36. The discovery of three novel loci for syndactylies will significantly help in the clinical and genetic delineation of this complex limb malformation. It will be of tremendous help to the families with limb malformations seeking genetic advice. The ultimate elucidation of the underlying genes might increase our understanding of limb development, especially in the context of getting insight into the developmental cascades of digit number, identity and separation

Consanguinity and Its Sociodemographic Differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan

Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe

Internal Corporate Governance Mechanisms and Agency Cost: Evidence from Large KSE Listed Firms

The purpose of the study is to analyze various corporate governance mechanisms that reduce agency cost. For the period 2003-2010 we have selected 120 firms on the basis of market capitalization listed on the “Karachi Stock Exchange”. We used two proxies’ asset utilisation and asset liquidity ratios to measure agency cost. A higher asset utilization ratio means lower agency cost whereas a higher asset liquidity ratio means higher agency costs. Board and committee activities, board size, CEO/Chair duality, CEO tenure, %Block ownership, %largest investor and debt financing are used as independent variables. The result shows that variables board and audit committee activities and asset utilisation ratio has strong positive correlation. However block ownership, board size, duality and asset utilization ratio appears to have negative correlation. When we use asset liquidity ratio as the dependent variable agency cost is reduced with frequent board meetings. The variables board size and CEO tenure has positive correlation with asset liquidity ratio. Block ownership and asset liquidity ratio has negative association. Furthermore variables duality, debt financing and largest investor has insignificant relation with asset liquidity ratio. Keywords: Asset Utilization Ratio, Asset Liquidity Ratio, Corporate Governance

Factors Affecting the Demand Side of Exports: Pakistan Evidence

The aim of this article is to investigate different factors affecting the demand of Pakistani exports. Factors affecting the demand of exports include real effective exchange rate, nominal exchange rate, world production capability and world export price variable. The period of the study is from 1990 to 2010. Data is gathered from various sources including State Bank of Pakistan, Karachi Stock Exchange, Handbook of statistics on Pakistan Economy, Economic Survey of Pakistan and International Financial Statistics (IFS). Two Stage Least Square (2-SLS) Method was applied in the study.  Results show that, export demand decreases with increase in Real Effective Exchange Rate. Insignificant relationship was found between the demand of Pakistani exports and export price variable and nominal exchange rate. The study also found positive and significant association between the demand of Pakistani export and World Income. Keywords: Export Growth, Foreign Direct Investment, Two Stage Least Square JEL Classifications: F13, F14, O1