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Elucidating the Genetic Basis of Neurological Disorders in Pakistani Population

Thesis Info

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Author

Zafar Ali

Program

PhD

Institute

Pakistan Institute of Engineering and Applied Sciences

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Natural Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/9029/1/Zafar%20Ali%20Thesis%20Final%20print.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726050485

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Human brain development is a complex process involving many cellular pathways. Pathogenic mutations in genes controlling as a whole or in parts, any of these cellular processes result in neurological disorders. It is basically due to defective signaling function in central or peripheral nervous system. The clinical features of such disorders are extremely diverse and overlapping, with even greater genetic heterogeneity. They may either be simple, having Mendelian inheritance or they may be complex. Genetic factors play very important role both in simple and complex neurological diseases. The consequences of such diseases are usually devastating both for affected individuals, their families and society, mainly by affecting the qualities which make human special as person; the character, memory, cognition, communication and skilled movements. In the present study, 11 consanguineous Pakistani families having neurological disorders of Mendelian inheritance were investigated using next generation sequencing (NGS) technologies. Rare and disease causing variants mostly occur in coding part of genome. Whole exome sequencing (WES) was used as a method of choice in the current study because of the heterogeneous nature of neurological disorders both clinically and genetically. Variants obtained from WES were prioritized based on their inheritance pattern, disease association, functional relevance and pathogenicity score as predicted by different bioinformatics tools such as Mutation Taster and PolyPhen-2. Segregation of all the variants were confirmed using Sanger sequencing. Ten novel and one already reported mutation were identified in this study. At present there are no effective treatment strategies available for most of these diseases. Therefore, identification of gene/s and pathogenic variant/s in these diseases will help understand underlying molecular mechanisms better, and lead to improved strategies both for genetic counseling and potential therapeutics
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دکھاں نے جد ماری سٹ

دکھاں نے جد ماری سٹ
تازے ہوئے جگر دے پھٹ
کیتے مول عمل نہ چنگے
خالی رہ گیا میرا مٹ
جو سٹی تھک منہ دے وچوں
بندا بن جا نہ اوہ چٹ
چار دیہاڑے ایہہ زندگانی
جیہڑی نیکی کھٹنی کھٹ
جیڈی آکڑ مستی ہووے
کڈھدی موت بندے دے وٹ
اوہو رب دے پیارے بندے
جیہڑے حق تے جاندے ڈٹ
بچ برائیوں جے وس لگے
مڈھوں اس دا بوٹا پٹ
عشق ساہنوں بنھ بنھ لے جاندا
سوہنے کہندے پچھے ہٹ
کدی وی عاشق بن نہیں سکدا
جو نہیں چڑھیا عشق دے بھٹ

تابعین کرام کا مقام و مرتبہ اور ان کی علمی و ادبی خدمات

After the Prophets of Allah Almighty, the most sacred class of mankind is the class of Prophet Muhammad's Companions. Those are the people who had seen the prophet of Islam with their naked eyes, remained in his companionship and got the heights of knowledge and actions and proved to be a great example of character by attaining the image of Prophet Muhammad's model of excellence. Another class which, like the companions of Prophet (pbuh), deserves such honor is the class of Tabe’en (The followers of the Companions).  Tabe'en had contributed a matchless role in the history of Islam regarding religious knowledge and literature. They had also examplary performed in social, economical, political and military services. Due to these great services they are considered the most sacred class of the Ummah after the prophet’companions. There is a list of academic and literary services ahead of the name of each person in this class. And these services are the great testimony to the greatness of these people. The prophet's companions received the religious knowledge directly from the Prophet (peace and blessings of Allah be upon him), while Tabe'en got it from the companions and then published it in the whole world. The sincere efforts performed by Tabe'en regarding Quran, Hadith, Tafseer and Islamic litrature are of so high level that no one had reached such level of sincerity in the entire history of Islam. The steps that occur after that period, regarding the development of Islamic culture are only the effects of their services. Actually ‘‘Tabe’en’’ is the only class that has spread the social, moral and spritual blessings of Islam throughout the world. That is why, it is not only the Quran that witnesses their greatness but the Prophet (peace be upon him) also praises them.

Transition Metal Doped Zns Based Photoactive Nanohybrid Material: Synthesis, Characterization and Applications in Hybrid Solar Cell

The thesis is divided into three chapters. Chapter 1 presents the background and surveys the current literature and also describes the principles behind the operation of PV devices. Chapter 2 presents the research methods and measurement techniques used in the study. Chapter 3 describes results and discussion and has six different sections. The first section comprises of the synthesis of zinc sulphide (ZnS) and Cd-doped ZnS nanoparticles, Zn1-xCdxS (x= 0.2-0.5), by wet chemical method. Optical, electrical and photovoltaic properties of the nanoparticles were investigated. A significant bathochromic shift of absorption band with respect to the un-doped zinc sulphide was noticed by increasing the cadmium concentration in the doped samples. Consequently, the band gap was tuned into the visible region. XRD analysis showed that the material existed in cubic crystalline state. The conductivity of the doped material, though progressively increasing step by step, was found lower than un-doped ZnS at cadmium contents ranging from 0.2 to 0.4 M but at the highest dopant concentration (Cd, 0.5 M) the conductivity attained a value higher than undoped ZnS by 1.21 × 10-5 Ω-1m-1. The overall % ɳ of the solar cell at 0.5 M Cd content in doped ZnS nanoparticles was found to be 2.33 times higher than the reference device (P3HT-ZnS) (Paper published in Journal of Photochemistry and Photobiology A: Chemistry). The second section describes the influence of dopant concentration on structural, optical and photovoltaic properties of Cu-doped ZnS nanocrystals. A significant blue shift of absorption band with respect to the un-doped zinc sulphide was sighted by increasing the Cu concentration in the doped sample with decreasing the size of nanoparticles. The synthesized nanomaterial in combination with P3HT, poly (3-hexyl thiophene) was worked in the fabrication of solar cells. The overall power conversion efficiency of the solar cell at 0.1 M Cu content in doped ZnS nanoparticles was found to be 1.6 times higher than the reference device (P3HT-ZnS), (Paper published in European Physical Journal Applied Physics). XXIV Furthermore, the third section depicts the synthesis, characterization and photovoltaic performance of Mn-doped ZnS nanocrystals. The PL emission centered at 596 nm is the characteristics emission of Mn2+ which can be attributed to a 4T1→6A1 transition within the 3d shell. The devices with ZnS nanocrystals showed an efficiency of 0.48% without annealing and 0.52% with annealing. By doping with manganese, the efficiency was enhanced by a factor of 0.52 without annealing and 0.59 with annealing. The morphology and packing behavior of blend of nanocrystals with P3HT were studied using Atomic Force Microscopy (Paper published in Optical Materials). Additionally, section fourth describes the effects of embedding un-doped and Mn-doped ZnS nanoparticles in the active layer on the performance of organic photovoltaics devices. The active layer primarily consists of various ratios of the organic electron donor poly (3-hexylthiophene (P3HT) and the electron acceptor [6, 6] phenyl-C61-butyric acid methyl ester (PCBM) together with nanoparticles dissolved in dichlorobenzene. The weight ratio of PCBM to un-doped and doped nanoparticles in the blend was varied, keeping the ratio of P3HT constant. The power conversion efficiency (PCE) improved by increasing the nanoparticle concentration in the active layer blend. The devices with ZnS nanocrystals (1:0.5:0.5) showed an efficiency of 2.42%. By doping with manganese, the efficiency was enhanced by a factor of 1.46 (Paper published in European Physical Journal Applied Physics). However, fifth section describes first time the direct observation of the nucleation and growth process of CdS nanowires by stirring of CdS nanoparticles. The growth process of CdS nanowires consist of three steps, the growth of CdS particles, nucleation of CdS nanorods and finally the growth of CdS nanowires. This method brings forward a new idea to synthesize nanowires. Furthermore, carboxylic functionalize porphyrin was examined as sensitizer for CdS nanowires. The hybrid devices were fabricated with organic polymer with different concentration of dyes and the device with optimum concentration 6×10-6 M shows the highest efficiency of 0.5% with short-circuit current density 3.10 mAcm-2, opencircuit voltage 0.44 V and fill factor 0.37 (Paper published in European Physical Journal Applied Physics). Last section of chapter 3 illustrates photocatalytic degradation of Alizarin Red S using ZnS and cadmium doped ZnS nanoparticles under unfiltered sunlight. Photo catalytic XXV degradation of Alizarin Red S (ARS) by the nanoparticles showed that the cadmium doped ZnS acted as a potential Photocatalyst under unfiltered solar light. The ARS dye was degraded about 50% and 96.7% in the presence of ZnS and Cd-ZnS (Cd, 0.5 M) nanoparticles respectively in 120 min. Furthermore the effect of various parameters, i.e., Photocatalyst concentration, dye concentration, and pH of the solution on the percentage of degradation was also studied. Degradation followed first order kinetics (Paper published in Surfaces and Interfaces).