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Home > Identification and in Silico Analysis of Genetic Polymorphisms in Gc & Vdr Genes in Vitamin D3 Deficient Pakistani Population

Identification and in Silico Analysis of Genetic Polymorphisms in Gc & Vdr Genes in Vitamin D3 Deficient Pakistani Population

Thesis Info

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Author

Shafiq, Hamid

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Molecular Medicine

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11538/1/Hamid%20Shafiq%20Biochemistry%202019.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726389810

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The sunshine vitamin is in the limelight for the last couple of years. Though Pakistan is located at favorable latitude and longitude yet vast majority of its people suffer from vitamin D deficiency. Calcium homeostasis, bone metabolism and many other functions of body are influenced by vitamin D. Nuclear vitamin D receptor and group specific vitamin D binding proteins are two important proteins play role in vitamin D metabolism and encoded by VDR and GC genes. There could be many reasons but in this study six single nucleotide polymorphisms in GC, VDR and CYP2R1 genes were looked into for their possible association with vitamin D deficiency. Blood samples of four hundred subjects were collected. Vitamin D and parathyroid harmone levels were calculated by chemiluminescence method. DNA extraction was carried out by phenolchloroform method. The qualitative and quantitative analysis of DNA was carried out on agarose gel electrophoresis. Tetra amplification refractory mutation system polymerase chain reaction was performed to genotype rs7041, rs4588, rs2060793, rs2282679, rs3847987, and rs7974353. Genotypic and allelic frequencies with relative risk was calculated. In Silico protein modelling, docking and analysis of rs7041 was done. Overall 77.5% subjects were found to be with vitamin D deficiency/insufficiency. There were 35% from newborn to 20 years age group, 88.8% from 21-40 years and 95.8% from to 41-60 years.Significant negative correlation was observed between vitamin D and parathyroid hormone levels. rs 7041 belonging to GC genes showed T>G polymorphism. Major allele was T and minor allele was G. Minor allele “G” with genotype GG could be a risk allele contributing in vitamin D deficiency. rs7974353 belonging to VDR gene showed T>A polymorphism. Though “TT’ was in high frequency in VDD subjects compared to control yet insignificant association with VDD was noted. RR for both alleles and genotypes TA and AA was not significant with reference to homozygous wild type TT (0.6 for AT, 0.7 for AA). Results might had been xxi sigificant if thenumber of subjects were more. Rest of the four SNPs showed equal frequency in control and cases and hence showed no association with vitamin D deficiency. In silico model of SNP rs 7041 showed variation in the 3D structure of protein because of replacement of asparctic acid by glutamic acid. This can explain the cause of VDD / VDI due to poor docking of vitamin D with its binding protein. Conclusion is that rs7041 and possibly rs7974353 are contributing to VDD / VDI in studied group. Results are supported by In silico analysis of rs 7041.
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نعت

ہنجو روواں یار دی خاطر
اس مدنی سرکارؐ دی خاطر
قاصد بنے رسولؐ پیغمبر
سوہنے اس دربار دی خاطر
ظاہر ہویا جگ تے آ کے
رب سوہنے دل دار دی خاطر
نورِ محمد ظاہر ہویا
اس دنیا گلزار دی خاطر
روندے رہے وچ غار حرا دے
اس امت گنہگار دی خاطر
دشمن دا وی پچھنا کردے
ٹُر گئے گھر بیمار دی خاطر
یار بلایا عرشاں اُتّے
اپنے خاص پیار دی خاطر
سجدے وچوں سر نہ چایا
اس حسینؑ سوار دی خاطر

خلع فسخ نکاح ہے یا طلاق فقہائے کرام کی آراء کا تجزیاتی مطالعہ Whether Khula is Dissolution of Marriage or Divorce Critical Analysis of the Views of Islamic Jurists

Islam is an entire way of life. It illuminates every facet of daily existence. There is no problem for which Islam has not provided a remedy. Every aspect of beliefs and ethics, including human affairs, has also been examined. Islam is the only religion on earth that can be compared the height of Western culture and civilization. People have become its slavish disciples in the most literal sense. To stay up with the rest of the world, they are creating new interpretations of Islam for this reason. Accepted wisdom is a benefit, but only within the bounds of Sharia. Otherwise, it is Shaytan's legacy. ۔(شیطان) One of the most significant and crucial stages in a person's life is the nikah. It is expressly covered in the Qur'an and Hadith. It is created necessary for sustaining human existence. It is referred to as the culmination of human life and one of the Prophet's (ﷺ) required Sunnas. However, one of the most despised actions is the dissolution of a marriage. Islam, however, differs from other faiths. It contains the entire procedure/laws for dissolving a marriage. The appropriate discussion of Talaq and Khula is illustrated by the jurists' use of Estihsan and Qayas. Recent years have seen various crises and a collapse in Pakistani society. Smear and family system disturbance are the main issues among them. "Nikkah" is the fundamental element of a family system; in reality, a family system is based on Nikkah. If this Nikkah is intact, the entire family system is stable; nevertheless, if this Nikkah is broken, not only is the family system traumatised, but the entire society begins to suffer. The summary of this thesis explains that the Islamic Ideological Council's recommendations have been reviewed in light of the non-Sharia practises of the judicial authorities in relation to Khula and judicial powers related to Khula, as well as an analytical study of the remarks and opinions of commentators and jurists, including future jurists, regarding Khula. Key Words: Khul‘a, Judicial Khul‘a, Tansīkh e Nikaḥ, Divorce, ‘Īddat.

Separation of Some Selected Alkali and Alkaline Earth Metal Ions by Inorganic Ion Exchangers

The work described in this thesis consists of the synthesis, characterization and application of the supported ion exchange materials for use in connection with the separation of lithium, rubidium, cesium and strontium ions from the nitric acid solutions. Some of these metals, especially the Li, are of immense importance due to their use in industrial and defense sectors being vital for a special type of atomic power plants, alloy making, hydrogen storage, heat-resistant ceramic technologies, pharmaceutical industry and power sources including the storage batteries. Such uses, naturally, are expected to lead to environmental issues with the envisaged environmental induction leading to deterioration of the latter. Increasing energy demands and hence more nuclear power production seems to be inevitable and feasible alternate. However such steps may result in the production of more than forty radioactive by-products including Rb86, 87, Cs134, 137 and Sr90. These radio nuclides with their high transport abilities are expected to find their way to water bodies and soils and thus incorporated into animals and human beings through the food chain. The present work describes separation of such hazardous metal ions from the effluents and thus suggests environmental remedial mitigation and control by using new types of materials and appropriate separation methodologies. For this purpose supported inorganic ion exchange materials based upon hexacyanoferrates of different metal ions were prepared and used for the separation of the lithium, rubidium, cesium and strontium ions from aqueous HNO3 solutions. Potassium iron(III) hexacyanoferrate(II) and potassium iron(II) hexacyanoferrate(III) supported on polymethylmethacrylate (PMMA) were prepared by impregnation-precipitation method. However silica gel supported potassium iron(III) hexacyanoferrate(II), potassium iron(II) hexacyanoferrate(III), potassium nickel(II) hexacyanoferrate(III) and potassium copper(II) hexacyanoferrate(III) were synthesized, by in-situ impregnation–precipitation of the silica gel, prepared from trans silicate a commercial sodium silicate product cheaply available in the local market. All the synthesized materials were characterized by FTIR, XRPD, SEM/EDX, CHNS, TGA and surface area analysis in addition to the solubility and stability studies using different solutions of the mineral acids. Using the synthesized ion exchange materials separation studies for each of the lithium, rubidium, cesium and strontium ions, in HNO3 solution, were conducted independently, by carrying out optimizations procedures for establishment of various factors on the separation processes, to elucidate effects of the changing concentration of the metal ion, extent of the ion exchange process, effect of temperature variations on sorption, xii sorption capacity and distribution coefficient determination under respective optimized concentration for each of the above mentioned ions. All procedures, as designed, were tested before undertaking actual separations using authenticated standard solutions. Results on these optimizations are presented and discussed. Distribution coefficient (Kd) values determined for each of the Li+, Rb+, Cs+ and Sr2+ sorption on each of the synthesized material suggested their metal ion removal efficiency. Distribution coefficient values of these metal ions on PMMA supported potassium iron(III) hexacyanoferrate(II) represented a decreasing order of the Kd values as Li+ < Rb+< Cs+< Sr2+ showing the maximum capability for the Sr2+ removal. Deviation in the above cited trend was observed in the case of PMMA supported potassium iron(II) hexacyanoferrate(III) as Kd values followed the trend Sr2+ < Li+ < Rb+< Cs+ showing the lowest distribution of the Sr2+. Distribution of the metal ions on silica gel supported potassium iron(III) hexacyanoferrate(II) indicated the lowest efficiency of the sorbent for Sr2+ removal, while alkali metals have shown minimum values of Kd for Rb+, intermediate for Li+ and highest for Cs+. Potassium iron(III) hexacyanoferrate(II) supported on silica gel has followed the order Li+<Rb+<Sr2+<Cs+, while silica gel supported potassium nickel(II) hexacyanoferrate(III) has depicted the decreasing order of the distribution coefficient values as Rb+< Li+≤ Sr2+< Cs+ showing the least capability for the Rb+ extraction, intermediate for Li+ and Sr2+, while maximum for Cs+. Efficacy of the silica gel supported potassium copper(II) hexacyanoferrate(III) was minimum for Li+ and maximum for the Cs+ as indicated by the Kd values which have shown the decreasing order Li+< Sr2+<Rb+<Cs+. Distribution coefficient values stated that the material PMMA supported potassium iron(III) hexacyanoferrate(II) appeared to be the best for the Sr2+ removal under respective optimized conditions. Maximum efficiency for the Li+ extraction was observed in silica gel supported potassium iron(II) hexacyanoferrate(III), while silica gel supported potassium copper(II) hexacyanoferrate(III) appeared to be the best for Rb+ removal. All the materials were found to be excellent Cs+ scavenger under respective optimized conditions. The results obtained have been discussed keeping in view the available information and stipulated use of some of these materials have been suggested for remedial mitigation of the environmental problems.