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Genetic & Molecular Basis of Inherited Visual Disorders

Thesis Info

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Author

Sheikh, Shakeel Ahmed

Program

PhD

Institute

Liaquat University of Medical and Health Sciences

City

Jamshoro

Province

Sindh

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Molecular Biology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/10512/1/Shakeel%20Ahmed%20Sheikh_Molecular%20Bio_2018_LUMHS_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726263444

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The inherited visual disorders are leading cause of blindness all over the world. In Pakistan, where consanguinity is common, high prevalence of genetically transmitted visual disorders is a serious health problem from socio-economic aspect. The present study was aimed to investigate the genetic and molecular basis of various inherited visual disorders in Pakistani population. For this purpose, we enrolled Twenty seven families suffering from Primary Congenital Glaucoma, Stargardt disease and Congenital Cataract from different cities of Sindh province. Blood samples were obtained from affected as well as normal individuals from all enrolled families and detailed medical history and ophthalmological examination were carried out. All families were first subjected to genotyping to known/reported loci or genes for Primary Congenital Glaucoma (PCG), Stargardt disease and Congenital Cataract. Whole Exome Sequencing (WES) was done for the families found not linked to any known locus/gene and candidate variants were subjected to direct Sanger sequencing for segregation with the disease phenotype. Seventeen families with PCG were enrolled for present study. Thirteen PCG families were found linked to CYP1B1 gene. Sequencing further revealed two novel mutations in CYP1B1i.e. p.G36D and deletion of 12 bp (p.G67-A70del) in PCG-08 and PCG-09 respectively. p.R390H was found in eight PCG affected families whereas p.E229K and p.R290fs*37 (c.868_869insC) was found once in two families. p.A115P was found in one family with four phenotypically normal homozygotes as well most probably due to either non-penetrance or reduced penetrance of CYP1B1. Four families remained unlinked to any reported locus or gene for PCG. Five Stargardt disease affected families and five families with Congenital Cataract were screened for linkage to known or common loci/genes. After excluding linkage to reported genes, WES for two Stargardt disease families revealed a novel gene ARL3, which has not been reported earlier. Likewise we carried out WES for a single congenital cataract and it was found linked to INPP5K, a novel gene and has recently been reported in association with syndromic form of congenital cataract in 2017. xvii In brief, the study reports CYP1B1 as most common mutated gene for patients with PCG in our population. Two novel mutations, a missense and a deletion in CYP1B1 were found, in addition to already reported mutations in other PCG families whereas a novel gene (ARL3) was identified in association with Stargardt disease. In Congenital Cataract, INPP5K (a novel gene when it was first identified in November, 2016) was found to be segregated with disease phenotype. All these novel findings are suggestive of genetic heterogeneity of Pakistani population for inherited visual disorders and genetic factors responsible for corresponding phenotype. The data may be beneficial for public awareness and genetic screening of our population to improve the prognosis of corresponding genetic disorder by early diagnosis. In addition, the findings of this thesis may contribute to already existing data on inherited visual disorders especially when no significant work in this regard has been carried out in people of Sindh province of Pakistan.
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غزل

 جیون کی

 

 اس درد کتھا کا

 

میں اک عنواں ہوں

 

میرے اندر صدیوں کا

 

سنتاپ چھپا ہے

 

میرے  باطن میں ہیں کتنے

 

 گہرے گہرے  درد  سمندر

 

جن کی تشنہ سی کچھ لہریں

 

میرے بنجر خوابوں کی

 

تعبیریں ڈھونڈ رہی ہیں

 

خواب سفر کی منزل

 

کتنی کٹھن ہوئی ہے

 

میں اس منزل کا راہی ہوں

 

اپنی ذات کے صحراؤں میں

 

سر گرداں ہوں

 

یعنی آج کا انساں ہوں میں

 

Educator Readiness Evaluation in the Implementation of Curriculum 2013 in Disadvantaged, Frontier, and Outermost Areas

This study aims to describe the readiness of educators in implementing the 2013 curriculum in the 3T area in North Gorontalo District. The method used in this research is descriptive qualitative method. The subjects in this study were school principals and educators in the 3T area school. The research result shows four things; first; Academic qualifications of educators in schools in the 3Tl area have not been fully fulfilled according to Law No. 20 of 2003 concerning the National Education System Article 42 paragraph (1). Second; The Academic Competence of Educators in the 3T area is not yet fully educated with S1 academic qualifications in accordance with Article 8 of Law Number 14 of 2005. The three certificates of educators have not been fully fulfilled in accordance with the mandate of Law Number 14 of 2005 concerning Educators and Lecturers. The fourth role of educators in realizing the goals of national education principals continues to encourage educators to continue to carry out learning innovations, especially in the implementation of the 2013 curriculum as an effort to improve professionalism as a form of role in realizing the goals of national education.

Determinants of Foreign Direct Investment Fdi and Policy Analysis. an Econometric Analysis. a Case Study of Pakistan

The rapid growth of literature on foreign direct investment is testimony to the increasing importance of the phenomenon as both a reality in daily life and a topic of inquiry within the academia. The debate over the advantages and disadvantages of foreign resources has occupied the attention of both scholars and policy makers. The literature on foreign direct investment (FDI) and development reveals more than its fair share of controversy, large part of this literature is unedifying and unscientific. Attitudes towards foreign direct investment have changed significantly since the early 1980s because of decreasing flows of other types of foreign capital, such as bank loans and foreign aid, and the increasing globalization of the world economy. Consequently, FDI has become increasingly the source of capital for developing and transition economies. Many countries are liberalizing their economies and implementing policy changes to participate more fully in the internationalization of production. The objective of this study is to understand the magnitude, direction, and rate of change, characteristics, impact and determinants of Foreign Direct Investment (FDI) in Pakistan’s economy and to quantify the key FDI determinants in dynamic econometric model from 1971-2003. We have tried to find out the relationship among the set of variables in context with macroeconomic variables and policy instruments. Our study also measured the causality direction among the set of key variables. Furthermore, we have measured the impact of policy changes in various structural periods i.e., 1979 Afghan war, 1988 structural adjustment program (SAP), and 1998 nuclear tests. This enabled us to know whether the liberalization policies significantly attract the large level of FDI inflows. We have reviewed the investment policies over the period 1971-2003 and their potential implications and trends on FDI. We have hypothesized that the degree of attraction of cost-related, investment environment, development strategy factors with ownership and internalization factors and other factors i.e. political risk, business conditions, historical trend of investment, impact of various investment policies on FDI, the relationship of domestic and foreign direct investment, as well as macro economic variables more likely to affect the FDI both qualitative as well as quantitative terms. The aim of this study is to understand, whether and at what extent the FDI reacts to some development characteristics of the country. Following hypothesis been tested i.e., (1) The high degree of attraction of cost related factors, the better investment environment factors, development strategy factors with ownership and internalization factors, more it will attract FDI. (2) The more stable socio political, economic conditions, the more likely that investment will take place. (3) The instable political scenario results in low investment. (4) The higher international transactions, increases in the inflows of FDI. (5) The more viable the development strategy and policies the more of FDI. (6) The more open the economy, more likely, the better chances of investment will take place. (07) The more liberal the economy is, the higher will be the inflows of FDI. (8) The higher the output growth, the more likely the investment will take place. (9) The availability of skilled work force both technical and managerial will induce FDI. (10) The high and good level of quality of infrastructure paves ways to the desired FDI inflows. This study has used the Co integration, VAR, and VEC methodologies, the Co- integration, VAR (Vector Auto Regressive), and VEC (Vector Error Correction) methodologies. 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