Human Genetics And Molecular Medicine - Master Dissertation

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/104

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Start date: 2018End date: 2018

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    Association of UGT1A6 2 (Ser7Ala) polymorphism with therapeutic response to aspirin in ischemic stroke patients
    (Central University of Punjab, 2018) Kumar, Dharmendra; Munshi,Anjana
    Ischemic stroke occurs due to the formation of thrombus or embolism within the arteries due to platelet aggregation. Aspirin therapy is used for the prevention of secondary stroke. The variant of UGT1A6 (Ser7Ala) gene has been found to be associated with ischemic stroke as well as aspirin resistance. We aim to study the demographic profile of ischemic stroke patients from Malwa region of Punjab and to evaluate the frequency of UGT1A6*2 Ser7Ala polymorphism and correlate it with aspirin resistance and ADRs (if any). We collected 30 samples from confirmed ischemic stroke patients from Guru Gobind Singh Medical College and Hospital in Malwa region of Punjab. DNA was isolated from blood and PCR- RFLP technique was used to evaluate the UGT1A6 gene variant in the patients. mRS value was used to classify patients as responders or nonresponders. 24 patients had TT genotype and 6 patients were found to bear TG genotype. 90% of patients were aspirin responders and 10% were aspirin nonresponders. Since the sample size was too low to identify significant associations, a large number of samples should be screened before coming to a conclusion. However, this preliminary study indicates that UGT1A6*2 (Ser7Ala) variant of UGT1A6 gene might be a risk factor for aspirin resistance in the studied group.
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    Analysis of exonic region of PCNT gene in Microcephalic Osteodysplastic Primordial Dwarfism Type II subjects
    (Central University of Punjab, 2018) Gupta, Neha; Khetarpal, Preeti
    MOPD II is an autosomal recessive disorder. It is characterised by the presence of intra uterine growth retardation as well as post natal growth retardation. The adult height is not more than 100 cm. It has been found that mutation in PCNT gene is associated with MOPD II. The cytogenetic location of this gene is 21q22.3 and it contains 47 exons. It encodes for PCNT protein which is a very large coiled scaffold protein and helps in microtubule polymerisation ensuring proper cell division. Till date 74 mutations have been identified this includes deletion, stop, frame shift and non sense mutation. The present study was carried out to analyse the exonic region of PCNT gene in Microcephalic Osteodysplastic Primordial Dwarfism Type II subjects. As it is an autosomal rescessive disorder both male and female were equally affected. The study included three subjects diagnosed with MOPD II .The DNA was extracted from whole blood and was amplified using locus specific primers. The products were sequenced using Sanger sequencing and were analysed. Total 12 variants were detected and 2 of which were pathogenic and 2 were synonymous and remaining 8 were polymorphic variants. 3 were present in exon 44 and 1 in exon 31 .These 3 variants were found to be present in all four subjects while 1 was present in only one subject. Change in nucleotide sequence may produce deleterious affect which is needed to be explored along with the complete structure of PCNT protein.
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    In Silico Design Of Compounds As Sglt2 Inhibitors
    (Central University of Punjab, 2018) Chakravorty, Kamaljyoti; Munshi,Anjana
    SGLT2 inhibitors (SGLT2i) are the current novel therapeutic approach expected to control the growing threat of type 2 diabetes mellitus (T2DM). With comparatively least reported side effects, SGLT2i (gliflozins) have been identified as promising tools to tackle the threat of T2DM. However, studies have also reported these drugs to cause renal impairments and urinogenital infections among certain T2DM patients. The efficacy of an inhibitor is fundamentally determined by the stability of protein-inhibitor complex. Therefore, it is essential to study the binding site residues of SGLT2 in the light of inhibitors' interactions. Structural insights of SGLT2 suggested a competitive inhibition of the ligand glucose (agonist) by the gliflozins. The inhibitory effect of SGLT2i reduces the renal reabsorption of glucose and promotes glycosuria. Consequently, a reduced plasma glucose level prevents the risk of hyperglycemia and further T2DM. In order to design potent inhibitors the structures of the available gliflozins (empagliflozin, canagliflozin, dapagliflozin and ertugliflozin) were analysed. Accordingly, a library of 44 fragment molecules was generated for interactive enumeration. A core ligand structure was designed based on the structural analysis of the gliflozin. A total of 3250 ligand molecules were obtained using schrodinger maestro v11.3. Docking results have shown ligand molecules exhibiting two different modes of inhibition. Set A molecules exhibited glyconic mode of interaction while set B molecules displayed aglyconic mode of interaction at the glucose binding site. The interactions of set B molecules are similar to that of the standard gliflozins and are expected to be less stable. Lesser stability of the protein- iv ligand complex perhaps lead to the reported side effects. On the other hand, set A molecules (with lower docking score) are expected to be much stable in terms of their interactions which differ significantly from that of the standard gliflozins. Therefore, set A molecules are the anticipated potent SGLT2 inhibitors expected to show reduced side effects.
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    Analysis of PCNT gene coding sequence in subjects with Microcephalic Osteodysplastic Primordial Dwarfism Type II
    (Central University of Punjab, 2018) Gautam, Saksham; Khetarpal,Preeti
    Pericentrin (PCNT) is a main scaffold protein of Centrosome. It is encoded by PCNT gene which comprises of 47 exons and its cytogenetic location is 21q22.3. PCNT is a large protein containing 3336 amino acids. In PCNT protein two coiled-coil domains are bounded by a non-coiled region. Various mutations like non-sense, stop and deletion in PCNT are linked with human disorder Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPDII). The current project was carried out with an objective to analyze the coding region of PCNT gene among MOPDII patients. The DNA extracted from blood was amplified using locus specific primers for 30 exons of PCNT gene. Amplified PCR products were sequenced using chain termination method and obtained sequence contigs were then analyzed by comparing with reference sequence. After analyzing - exon sequence contigs in 3 subjects, 17 variants were identified. There is need to amplify remaining 17 exons of PCNT gene for the identification of novel mutation in subjects with MOPDII. Homozygous or compound heterozygous PCNT mutation could not be identified in our study in the PCNT coding region covered
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    Psychological Burden Faced By Vitiligo Patients: A Comparative Study In Kerala And Punjab
    (Central University of Punjab, 2018) G, Ameetha; Chander, Harish
    Vitiligo is a common chronic skin disease having unknown aetiology, which causes a disfigurement and variable amount of skin and hair depigmentation and may affect a patient?s quality of life. To assess the psychological burden and epidemiologic profile of various age groups of patients affected by vitiligo in the southernmost district of the coastal state of Kerala and southern part of Punjab. All were investigated in a door- to- door survey. The questionnaire consisted of two sections, including psychological burden and their epidemiologic profile of various age groups. The questionnaire assigned contained questions about vitiligo characteristics such as the body surface area affected, skin tone, affected by genital vitiligo or not, marriage life and their sexual relationship, stigmatised conditions facing, whether or not affected areas were covered by dresses. 40% of males and 60 % of females were affected by vitiligo in Kerala but in Punjab males were more affected than females i.e. 60% and 40% respectively. The present study revealed that in Kerala and Punjab 25% of vitiligo patients were reported within the age group of 51-60 years and 20% within the age group of 21-30 years. More than 25% patients in Kerala and Punjab were fully affected with the vitiligo and the quality of life was impaired more in those patients and to a greater extent in women is more seen. About 76% of patients admitted of feeling self-conscious about their skin in Kerala whereas in Punjab 24% were affected.
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    Identification of Novel lncRNA in Breast Cancer Cell Line
    (Central University of Punjab, 2018) Sharma, Divya; Singh,Sandeep
    Long non-coding RNA(lncRNA) is RNA transcript having size of more 200 nucleotides and low number of exons are present due to which it expressed at lower level in specific tissues. Mainly the lncRNA is involved in gene regulations such as epigenetic regulation, chromatin remodeling and posttranscriptional regulations.The localization of lncrna is mainly in nucleus but there is considerable amount of lncrna present in cytoplasm. Lncrna can also target the mitochondrial genome. Identification of the targets of lncrna on mitochondrial genome helps to find the relationship between lncrna and mitochondrial functions which further helps in diagnosis and in therapy of the mitochondrial related diseases. One such lncRNA is MIR503HG, which act as a tumor suppressor in breast cancer cell line. Expression of lncRNA MIR503HG was analyzed in normoxic and hypoxic conditions upon the treatments of three different types of drugs on breast cancer cell line. The study of expression level of lncRNA MIR503HG in breast cancer cell line suggest a new cancer biomarker.
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    Evaluation Of Association Of Folic Acid Metabolism In Chronic Obstructive Pulmonary Disease
    (Central University of Punjab, 2018) Chaudhary, Deepti; Senapati, Sabyasachi
    COPD is characterized by increasing breathlessness. It is the fourth cause of death in the world and it is currently presenting a major global public health challenge, causing premature death from pathophysiological complications. It continues to be an important cause of morbidity, mortality, and health-care costs worldwide. It is a global health issue, with cigarette smoking being an important risk factor universally with several other factors, such as exposure to indoor and outdoor air pollution, occupational hazards, and infections. As the global population ages, the burden of COPD will increase in years to come. Folic acid or vitamin B9 is a water soluble vitamin plays a major role in metabolism. Since, COPD is a disease characterized by complex nutritional abnormalities and lower level of vitamin B9 and B12. Homocysteine or total homocysteine is a sulfur containing amino acid, acts as an intermediate in the metabolism of methionine in the folic acid or folate pathway. As observed among general population hyperhomocysteinaemia (mild to moderate), is mainly associated with vitamin B deficiencies, which are considered to be essential cofactors for the level and catabolism of hcy. Assessment of level of micronutrients is useful in establishing effects in COPD.
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    Meta-analysis and estimation of gene expression to establish the role of SFTPD in COPD
    (Central University of Punjab, 2018) Nandy, Debparna; Senapati, Sabyasachi
    COPD is considered to be third leading cause of death by 2020. So far, there is no proper biomarker available for the diagnosis of all the different sub-phenotypes. Multiple GWAS studies have reported the role of SFTPD (both genetic and serum protein) as a diagnosis biomarker. This current study aims to systemic - review and meta-analyse the association of anthropometric parameter (Smoking status, gender), Protein biomarker (serum SFTPD) and genetic biomarker (SFTPD rs721917) with COPD and its other phenotypes. To support the secondary findings, this study also aims to analyse the expression of SFTPD gene among COPD cases and healthy control from North Indian population. So far bronchodilators therapy are available for providing temporary relief to the patients. But bronchodilators are found to be associated with multiple number of side-effects. Indian Traditional medicine options like Ayurveda and yoga has lot to offer in this case. Many local Indian herbs are found to be significantly effective against COPD condition. Most importantly this herbs don't have any side effects. Pranayama and Dhyana have also been found to be improving Lung functions in multiple studies.
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    Potential Mitochondrial-Specific Function Of piRNAs
    (Central University of Punjab, 2018) Paul, Shouvik; Singh, Sandeep
    Piwi-interacting RNAs (piRNAs) are (26-31 nt) small noncoding RNAs processed from their longer precursor transcripts with the help of Piwi proteins. There are more than 30,000 piRNA genes present in the human genome which now turns out to be emerging player in both homeostasis and diseases. Localization of piRNA and PIWI in the repeat region of the mammalian nuclear genome in germ cells has been reported, although localization and potential functional role of piRNA in the mammalian mitochondrial genome are largely unknown. We have taken 111 piRNA sequences found in the MCF-7 mitochondrial genome, which is obtained by NGS analysis for alignment study. Resulting piRNA have been aligned with DQ112870 North American Homo sapiens mitochondrion genome for studying post- transcriptional roles of piRNA.
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    Bioinformatic Analysis of Whole Exome Data
    (Central University of Punjab, 2018) Md Momin Ali; Khetarpal, Preeti
    Whole Exome Sequencing (WES) is a capture-based method developed to sequence exome and to identify variants in the coding region of genes that affect protein function. Understanding the exomes of individuals at single base resolution allows the identification of pathogenic variants responsible for causing genetic disease. In this paper we mentioned all the object of the project steps and bioinformatic computational tools involved step by step. The objective of the study was to find all the disease causing heterozygous variants in the proband from the WES data. Using in silico tools SIFT, PolyPhen and ANNOVAR. All the annotated non-synonymous SNPs was arranged and filtered according to the pathogenicity of variants. All the variants were narrowed down to five matching variants. associated with clinical phenotype of the proband. As a conclusion Bioinformatic analysis of WES data proved to be a good tool for finding disease causing variants. Majority of the tools used in the analysis are generally linux based with poor user interface which makes it a challenging experience for a non-computational individual. Future of this field is dependent on software developers, so that more people can understand and help in the progress.