Day 1 :
Keynote Forum
Andreas Scherer
Golden Helix, USA
Keynote: Utilizing cancer sequencing in the clinic: Best practices in variant analysis, filtering and annotation
Time : 10.10-10.40
Biography:
Andreas Scherer is CEO and President of Golden Helix, a leading software company empowering high-end genetic analytics. He has managed global software and services businesses working for companies such as Netscape and AOL as well as privately held companies. As part of his academic work, he has developed algorithms to conduct DNA sequence analysis. He is author and co-author of over 20 international publications and has written books on project management, the Internet and artificial intelligence. His latest book, “Be Fast or Be Gone” is a prize winner in the 2012 Eric Hoffer Book Awards.
Abstract:
This talk focuses on how to build effective cancer gene panels utilizing state of the art filtering and visualization techniques. It covers the usage of public data sources such as Cosmis and Clinvar. Also, it outlines how to best build custom databases to capture specific findings in the clinic that can be used as future annotation sources. We cover how clinically vetted workflows can be embedded in automated pipelines to increase throughput. Now as the field move beyond gene panels, what is the clinical yield of whole exome and genome sequencing in this context? What can we expect in the future? As we move beyond gene panels the chances of incidental findings increases. What are the best practices to handle those? Finally, we cover how best to structure patients reports to separate results with high degree of certainty from findings that are of uncertain clinical relevance.
Keynote Forum
Krishna Dronam Raju
Foundation for Genetic Research, USA
Keynote: The role of Genomics in Gene Therapy and Diagnostic testing and related intellectual property issues
Time : 10:55-11:25
Biography:
Krishna Dronamraju is the Founder of The Foundation for Genetic Research in Houston which was founded in 1992, who is the President and Director of thernFoundation. Previous Advisors to the Foundation include Sir Arthur C Clarke, well known Author of many books in science and science fi ction; Dr Victor McKusick,rnMD, Chairman of the Department of Medicine, Johns Hopkins University School of Medicine. Current Advisors include Professor M S Swaminathan, Advisor to thernPrime Minister, and Chairman of the M S Swaminathan Research Foundation in Chennai, India; and Professor N A Mitchison, at the University of London, UK. Hernhas been nominated for the Nobel Prize. He was a Member of the US Presidential Delegation led by President Bill Clinton to India in 2000. He received his PhDrnin Genetics for research under the direction of the famous scientist J B S Haldane, who is well known as a polymath, a Founder of population genetics, and as arnprolifi c Author of numerous popular scientifi c essays.
Abstract:
Gene therapy has consistently failed to achieve its therapeutic potential. However, Genomics is now making it increasingly possible to manipulate real-world DNA, leading to the treatment of hereditary and acquired genetic disease. This is the beginning of a new era of genetic manipulation which will have clinically beneficial applications. However, intellectual property issues continue to plague the definition of gene and gene therapy . Critics have pointed out that gene patents fail to meet the criteria of intellectual property. Genes are naturally occurring, and while much intellectual effort may have gone into discovering them within the DNA sequence, discovery is not the same as invention. The location of a gene never met the criterion for being non-obvious. DNA patenting has proven to be a very active area, however, at least a fifth of the human genome is subject to patent claims.
Keynote Forum
Rosemarie Wahl
St. Mary’s University, USA
Keynote: Epigenesis, Methylation, and Single Strand Breaks
Time : 11:25-11:55
Biography:
: Rosemarie Wahl, Ph.D., earned a BS degree in Quantitative Biology from MIT, a MS degree in Biochemistry and a Ph.D. in Microbiology from the University of Chicago. She has been a faculty member at the University of Illinois at Chicago Circle, Texas Christian University, the University of Texas at Austin and St. Mary’s University. She was Chair of the Department of Biological Sciences at St. Mary’s University for 25 years (1979-2004), and is currently Professor of Biology. Her research contributions are in the molecular structure of bacterial viruses, the chemical basis of genetic mutation and the mechanism of DNA replication.
Abstract:
In vivo enzymatic methylation of cytosine in DNA is one molecular mechanism of epigenetic modification of gene expression. Epigenetic imprinting refers to the silencing of the genes from one parent, accomplished by DNA inactivation. The pathway following chemical methylation is: methylation of a purine→ apurinic sites→ single strand breaks→ double strand breaks (scission). Our studies of in vitro methylation of DNA isolated from the bacterium Bacillus subtilis indicate that single strand breaks account for all the inactivation of methylated purines. The methylating agent was the chemical mutagen methyl methane sulfonate (MMS). Biological inactivation was detected by decrease in transforming activity at the indole locus. Single strand breaks were detected by sedimentation velocity analysis of denatured DNA. DNA methylated to 1, 3 and 5 inactivating hits/ locus and denatured, gave S20 values of 17.8, 11.2 and 6.8 respectively, compared to 33 for denatured untreated control DNA. The S20 value and molecular weight of native double stranded DNA that had been alkylated to the same level showed no such decrease, indicating that the double stranded DNA molecule remained intact, despite the single strand breaks. Control studies with the enzyme DNase, known to cause single strand breaks exclusively, produced the same S20 value fragments after denaturation, when treated to the same level of inactivation. Since single strand breaks appear to account for all inactivation by MMS, it follows that alkylated purines or apurinic sites cannot account for any inactivation. This supports the methylation of cytosine at CpG sites as the epigenetic inactivating event.
- Track 6: Clinical Genomics Track 7: Micro RNA Analysis
Chair
Gopal B Krishnan
Promega Corporation, USA
Co-Chair
Peter Lajos Nagy
Columbia University, USA
Session Introduction
Tamer A Gheita
Cairo University, Egypt
Title: Clinical significance of serum interleukin-23 and A/G gene (rs17375018) polymorphism in Behçets disease: Relation to neuro-Behçet, uveitis and disease activity
Biography:
Tamer A Gheita (MD) is a Professor of Rheumatology & Clinical Immunology at Kasr Al-Ainy School of Medicine, Cairo University. He attained the EULAR Certifi cate for Rheumatic diseases, Zurich, Switzerland (2012) and is Editor-in-Chief of the Egyptian Rheumatologist (Elsevier). He is serving as an Editorial Board Member of the European and African Journals of Rheumatology, International Journal of Rheumatic Diseases and the Annals of Pediatric Rheumatology. He has published more than 80 papers in reputed journals and several books. He is a Consultant at many JCI accredited hospitals and shared in several medical convoys to underprivileged communities.
Abstract:
Objective: Th e aim of this work was to measure the level of serum Interleukin-23 (IL-23) and assess its genotypes in Behçets Disease (BD) patients and to study the clinical signifi cance and relation to disease activity. Patients & Methods: Fift y BD patients and 30 age and sex matched controls were included. Disease activity was assessed using BD Current Activity Form (BDCAF). Serum IL-23 was quantifi ed by ELISA and (rs17375018) genotyping performed by real time PCR-allelic discrimination technique. Results: Th e serum IL-23 level was signifi cantly higher in patients compared to the control (p<0.0001). Th e IL23 genotypes were comparable between patients and control. Genotype in neuro-Behçets patients was AA (5.3%), AG (36.8%) and GG in 57.9% and those without: AA (22.6%), AG (35.5%) and GG (41.9%). Th ose with uveitis had AA (8.3%), AG (33.3%), GG (58.3%) while those without had AA (23.1%), AG (38.5%) and GG (38.5%). Th e IL-23 level according to the three genotypes was insignifi cantly diff erent (p=0.18). Th e BDCAF was signifi cantly lower in those with AA genotype (1.88±1.13) compared to AG (2.06±1.39) and GG (3.17±1.49) (p=0.02). IL23 level signifi cantly correlated with the BDCAF (r=0.62, p<0.0001) and disease duration (r=0.42, p=0.002). Conclusion: Th is is the fi rst study to report the possible role played by IL-23 and its gene polymorphism in neuro-BD and not only uveitis with a signifi cant relation to disease activity, making both potential markers. Larger scale multi-centre longitudinal studies are required to confi rm its role in the pathogenesis of neuro-Behcet’s and its impact on response to therapy.
Wenju Wang
Yan’an Hospital of Kunming City, China
Title: Investigation of proliferation and cytotoxicity capacity of cytokine-induced killer cells: Omics strategy
Biography:
Wenju Wang has completed his PhD from Peking Union Medical College and Postdoctoral studies from Institute of Zoology, Chinese Academy of Science. He is an Associate Professor of Cancer Immunotherapy at Yan’an Hospital of Kunming City and Yunnan Cell Biology & Clinical Translation Research Center. Currently, his researches focus on developing novel antigen-specifi c immune cells against tumors.
Abstract:
Clinical trials of Cytokine-Induced Killer (CIK) cells based immunotherapy against cancer are widely performed in China. However, the mechanism of CIK cell proliferation and acquisition of cytolytic function against tumor have not been well elucidated yet. We compared the proliferation and tumor toxic capacity between CIKIL-2 and CIKIL-15. By employing microarray, we analyzed miRNA expression profi les of PBMCs, CIKIL-2 and CIKIL-15. Moreover, RNA-seq was performed to identify diff erentially expressed genes between CIKIL-2 and CIKIL-15. Th e results indicated that CIKIL-15 showed improved cell proliferation capacity compared to CIKIL-2. However, CIKIL-2 has exhibited greater tumor cytotoxic eff ect than CIKIL-15. Bioinformatic analysis indicated that miR-143-3p/miR-145-5p was miRNA cluster which may positively regulated cell proliferation. In contrast, miR-340-5p/miR- 340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIKIL-2. Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1 which may restrict cytotoxic function of CIK. Employing deep sequencing, a total of 374 diff erentially expressed genes (DEGs) were identifi ed. Among DEGs in CIKIL-15, Wnt signaling and cell adhesion were signifi cant GO terms and pathways which related with their functions. In CIKIL-2, type I interferon signaling and cytokine-cytokine receptor interaction were signifi cant GO terms and pathways. We found that inhibitory signal from interaction between CTLA4 and CD80 may be responsible for the weak proliferation capacity of CIKIL-2. Our fi ndings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function.
Gopal B Krishnan
Promega Corporation, USA
Title: Simplified and improved RNA workflow tools to study RNA
Biography:
Gopal B Krishnan completed his PhD from the National Institute of Immunology, New Delhi and has worked on Early Embryonic Development and Role of Bone Morphogenetic Proteins in his Post-doctoral Fellowship at the University of Wisconsin, Madison. Before joining Promega Corp, he worked as the Team Lead for Development of DNA and siRNA transfection reagents at Mirus Bio. Currently, he is a Global Product Manager of genomics products at Promega Corp., Madison, WI. He has published over thirty peer reviewed articles, chapters and abstracts. In addition he has successfully launched fi ve new life science research products.
Abstract:
Micro RNAs (miRNAs) along with small interfering RNAs and several classes of non-coding RNAs (example snRNA, snoRNA and piRNA) have widespread impact on a variety of biological processes. miRNAs are an important class of small RNAs that regulate gene expression. While most of the known mammalian miRNAs have been characterized using cloning and sequencing, there are still many with unknown functions. In general, the analysis of small RNAs and their expression is a critical part of many research studies due to the signifi cant role played by miRNA in controlling vital pathways such as growth, development and death. Much interest has been directed at studying the expression of miRNA in cells and tissues as well as bodily fl uids. Increasing eff ort is directed into bio-informatic prediction of new miRNA sequences. A combination of computational biology tools and molecular cloning methods is being used for characterizing additional miRNAs. However, isolating the mature miRNA fraction is the fi rst critical step in cloning these small regulatory molecules. Th e presentation will focus on tools developed to study small RNA including non-organic reagent based purifi cation methods that ensure high yields of pure RNA protected from RNase degradation and accurately quantify RNA to use in varied down-stream applications such as quantitative RT-PCR, arrays and sequencing. While most traditional RNA isolation methods are not very effi cient at recovering these smaller RNAs that contain 17-24 nucleotide mature miRNA, the RNA workfl ow employed along with this purifi cation method ensures high quality total RNA with enhanced miRNA enrichment from a variety of sample types.
Peter Lajos Nagy
Columbia University, USA
Title: Practical approaches for increased specificity and sensitivity of clinical next generation sequencing testing
Biography:
Peter Lajos Nagy is a biochemist and a physician, board certified in anatomic and molecular genetic pathology. His research focuses on the role of transcriptional processing in the pathogenesis of neurodegenerative disorders. He developed S. pombe and M. musculus models for Ataxia-Oculomotor-Apraxia type 2 (AOA2) caused by mutations in the human ortholog of the yeast RNA helicase Sen1, Senataxin (SETX). Using these models we are working to define the pathomechanism of SETX mediated neurodegenerative disorders AOA2 and ALS4.
Abstract:
Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to off er clinical Whole Exome Sequencing (WES) in January 2013. We processed and issued reports on over 500 cases mostly trios. Next-generation sequencing in the clinical practice allows for a critical review of the literature describing the pathogenicity of specifi c mutations or the disease relatedness of specifi c genes and also provides an important discovery tool for new disease genes and disease causing mutations. Because of the large volume and complex nature of the data obtained from large panels and whole exome sequencing testing, the management of the data in a transparent, yet powerful analytical framework is a key to successful clinical operation. Population allele frequency, data from parents and precise, yet concise phenotypic description are the corner-stone for successful clinical evaluation of the pathogenicity of variants identifi ed. Th e full potential for discovery of new disease associated genes and disease causing mutations can only be realized if there is a tight collaborative eff ort between the clinicians performing the interpretation and structural biologists and analytical chemists and cell biologists who can help predict and verify the eff ects of variants identifi ed. Th rough my presentation, the audience will obtain an understanding of the current state of the art of clinical genomic testing; will become familiar with the major factors that determine the precision and sensitivity of pathogenic mutation detection; have a thorough understanding of the importance of proper implementation of structural and functional basic science data sources into the clinical analysis pipeline. I will outline the contribution of clinical data collection to discoveries in basic science and review the obstacles to and opportunities for more effi cient collaboration between clinical medical centers and the pharmaceutical industry.
Zuhier Awan
King Abdulaziz University, Saudi Arabia
Title: Familial hypercholesterolemia in the Middle East: What have we learned recently?
Biography:
Zuhier Awan is a Physician-Scientist at King Abdulaziz University and an Adjunct Professor at McGill University. He has completed a combined training in Internal Medicine and Medical Biochemistry at McGill University and a Postdoctoral Fellowship in Cardiovascular Genetics followed by a Fellowship in Preventive Cardiology and Advanced Clinical Lipidology. Later, he earned both MSc and PhD degrees with honors from the Department of Biochemistry and Molecular Medicine from University of Montreal and did his thesis in PCSK9 and the Prevention of Cardiometabolic Disease in Familial Hypercholesterolemia
Abstract:
Introduction: Th e chronicles of Familial Hypercholesterolemia (FH) in the Middle East started sixty years ago with the fi rst description of Essential Hypercholesterolemia in numerous Lebanese families by Khachadurian et al in 1962. Later, the fi eld of FH and atherosclerosis expanded exponentially with numerous reports of mutations. FH became the number one cause of genetic Cardio-Vascular Disease (CVD) worldwide. Method & Results: Th rough follow up and close observation of the status of FH in the Middle East and North African (MENA) countries have shown a global under reporting, poor management and premature death in obvious genetic FH cases. Furthermore, emergence of the third culprit PCSK9 gene associated with FH by eff orts of Middle Eastern scientists has fl ourished the concept. Finally, surveillance of FH cases had aided in the understanding of the incidence of aortic calcifi cation and the essential role of infl ammation as a neglected marker and target of therapy in these individuals. Conclusion: Eff orts to establish a registry and cascade screening for FH in the MENA countries is undergoing to improve the recognition of cases in the MENA communities, increase awareness of the number one genetic risk for CVD and prevent premature atherosclerosis in FH. Th is registry will positively identify novel FH mutations which will have remarkable implications in the care of FH in this region and the world.
Cheng-Han Tsai
National Yang-Ming University, Taiwan
Title: Title: Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA
Biography:
Cheng-Han Tsai has completed his PhD from National Yang-Ming University and now is the fi rst year Post-doctoral studies from the same institute. His studies focuses on changes of physiological characteristics as well as related genes profi le including miRNA of lung cancer cell in vitro and in vivo while the actin associated protein, ADF/cofi lin is manipulated. Some of studies have been published on reputed journals and other manuscripts are under prepared for further submissions
Abstract:
Cofi lin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofi lin family is known to aff ect cancer development. Previously, we found that over-expression of cofi lin-1 suppressed the growth and invasion of human Non-Small Cell Lung Cancer (NSCLC) cells in vitro. In this study, we further investigated whether overexpression of cofi lin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specifi c microRNA would be involved in this event. Th e results showed that over-expression of cofi lin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were signifi cantly suppressed by over-expressed cofi lin-1, and down-regulation of Matrix Metalloproteinase (MMPs) 1 and 3 was concomitantly detected. According to the microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were apparently up-regulated among 248 microRNAs that were aff ected aft er over-expression of cofi lin-1 up to 7 days. Knock-down of let-7b or let-7e using chemical Locked Nucleic Acid (LNA) could recover the growth rate and the invasion of cofi lin-1 overexpressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofi lin-1 overexpressing cells, and Twist-1 was signifi cantly suppressed under this condition. Up-regulation of let-7 microRNA by overexpressed cofi lin-1 could be eliminated by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7 microRNA would be involved in over-expression of cofi lin-1 mediated tumor suppression in vitro and in vivo.
- Track 1: Biomarkers & Molecular Markers
Chair
Patricia E Berg
George Washington University Medical Center, USA
Co-Chair
Igor A Sobenin
Russian Cardiology Research and Production Complex, Russia
Session Introduction
Margarita A Sazonova
Russian Cardiology Research and Production Complex, Russian Federation
Title: Investigation of blood cell mitochondrial genome mutations in symptomless atherosclerosis among women
Biography:
Sazonova M A graduated from Kharkov State University in 1986. She defended her PhD thesis in 1999. From 1986 to 2005, she worked in the laboratory of molecular genetics of Human Genetics Institute of Research Centre of Medical Genetics RAMS, investigating molecular genetic features of cystic fi brosis and the frequency of somatic mutations in gene K-ras in patients with adenocarcinoma of colon. Currently, she is working as a Senior Researcher in the laboratory of angiopathology at Institute of General Pathology and Pathophysiology in Moscow, where she deals with the analysis of mitochondrial genome mutations in atherosclerosis. She has 115 publications to her credit.
Abstract:
Objective: Nowadays, atherosclerosis is one of the most common diseases. It is a basis for the majority of cardiovascular pathologies. Th e aim of the present study was a detection of mitochondrial genome mutations associated with symptomless atherosclerotic lesions of carotid arteries in women. Methods: Th e participants of the study were 183 conventionally healthy women from Moscow region, having no clinical manifestations of atherosclerosis in the form of coronary heart disease, old myocardial infarction or stroke. Th e age of the women varied from 34 to 86 years, the average age in the selection was 65.41(SD=9.34) years. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid Intima-Media Th ickness (cIMT). DNA samples were obtained from whole venous blood. In the present selection, 42 mitochondrial genome mutations were analyzed. Fragments of DNA were amplifi ed by PCR and further analyzed by new original method of quantitative assessment of mutant allele, developed in our laboratory on the basis of pyrosequence technology. Conclusion: Three atherogenic mutations (C3256T, G14709A and G12315A) and two anti-atherogenic ones (G13513A and G14846A), which are associated with symptomless (preclinical) atherosclerosis in women, were found.
Patricia E Berg
George Washington University Medical Center, USA
Title: BP1: A potential oncogene overexpressed in cancer
Biography:
Patricia E Berg received her Bachelor’s degree in Mathematics from the University of Chicago, her PhD in Microbiology from the Illinois Institute of Technology then pursued Post-Doctoral studies at the University of Chicago. A research at the National Institutes of Health followed. Currently, she is a Professor of Biochemistry and Molecular Medicine at George Washington University in Washington, DC where she is Director of a Cancer Research Laboratory. Her work which centers on the BP1 gene has been published in major journals and has been featured on network television and in major media including the New York Times and Washington Post.
Abstract:
BP1, a gene we identifi ed and cloned is a member of the homeobox gene family of Transcription Factors (TF). BP1 is overexpressed in breast cancer, prostate cancer, ovarian cancer, acute myeloid leukemia, non-small cell lung cancer and possibly other malignancies as well. Important characteristics of BP1 in breast cancer include: (1) BP1 is expressed in 80% of invasive ductal breast tumors including 89% of the tumors of African American women compared with 57% of the tumors of Caucasian women. (2) BP1 expression correlates with the progression of breast tumors, from 0% in normal breast tissue to 21% in hyperplasia and 46% in ductal carcinoma in situ. (3) Expression of BP1 is associated with larger tumor size. (4) BP1 appears to be associated with metastasis. Forty-six cases of infl ammatory breast cancer were examined and all were positive for BP1 expression as well as matched lymph nodes in the nine metastatic cases. (5) BP1 overexpression induces oncogene expression including BCL-2, VEGF and c-MYC as well as other genes important in angiogenesis, invasion and metastasis. pBP1 down-regulates BRCA1 and (6) BP1 up-regulates ER alpha and induces estrogen independence. High pBP1 levels can lead to estrogen independence in ER positive breast cancer cells and tumors in mice. In summary, BP1 appears to confer properties on breast cancer cells that lead to a more invasive and aggressive phenotype. Since the functions of homeotic TF are highly conserved, it is likely that BP1 regulates many of the same processes and genes in other malignancies.
Igor A Sobenin
Russian Cardiology Research and Production Complex, Russia
Title: Mitochondrial DNA variation in atherosclerosis
Biography:
Igor A Sobenin has got his MD in 1988 (Chelyabinsk State Medical Institute, Russia), PhD in 1991 (Russian Endocrinology Research Center), and DSc in 2006 (Institute of General Pathology and Pathophysiology, Russia). Now, he is a Leading Researcher at Russian Cardiology Research and Production Complex (Moscow, Russia). His research activity is in a fi eld of molecular and cellular mechanisms of atherosclerosis, genetic and phenotypic markers of susceptibility, clinical, epidemiological and population studies in the fi eld of atherosclerosis. He has over 200 published papers, among them over 120 are in international peer-reviewed journals.
Abstract:
In human pathology, several diseases are associated with mutations in the mitochondrial genome (mtDNA). Genetic predisposition plays an important role amidst the other risk factors in the development of atherosclerosis, a socially signifi cant multifactorial disease. Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. Conclusions: Th e focality and mosaic character of atherosclerotic lesions in human aortic intima may be due to the diff erences in the heteroplasmy level of mtDNA mutations to a great extent, and a certain profile of pro and anti-atherosclerotic mutations of mitochondrial genome is characteristic for diff erent types of atherosclerotic lesions. Th e presence of heteroplasmic nonsynonymous mtDNA mutations may lead to mitochondrial dysfunction in specifi c sites of intimal tissue. Th e data obtained in clinical study can be used to assess individual risk of atherosclerosis, as well as for further studies on the role of mitochondrial genome mutations in the development of atherosclerosis and its clinical manifestations. Th e individual profi le of certain mtDNA variants may partially explain atherosclerosis variability and genetic predisposition to atherosclerosis in population, which could be inherited by maternal line.
Afsheen Arif
University of Karachi, Pakistan
Title: CFC1 gene mutation in tetralogy of fallot and dextro-transposition of great arteries in Pakistani population
Biography:
Afsheen Arif has completed her Ph.D. (Biotechnology) in 2013 from The Karachi Institute of Biotechnology and Genetic Engineering, KIBGE, University of Karachi and currently working as an Assistant Professor. She had more than 12 years of research experience. She has expertise in biotechnology, genetics and molecular biology. Research is her passion and she has keen interests are to study molecular genetics of rare diseases. She has ten publications in reputed journals. In Future, She would like establish stem cell and regenerative medicine laboratory.
Abstract:
Congenital heart diseases (CHDs) are the most common of all birth defects and one of the leading causes of mortality in the fi rst year of life. CFC1 gene is a cell signaling protein and it is a co-receptor in nodal signaling pathway and involve in right and left axis determination during gastrulation. Th is is a case control study, recruited 175 non syndromic patients and 140 controls, healthy unrelated individuals. Th e study aft er formal approval includes patients from various pediatric cardiology centers in three years. A detailed family history was taken to elucidate the genetic and environmental factors. Pediatric cardiologist confi rmed the diagnosis on the basis of all standard testing like chest X-ray, CBC, ECG, ECHO, heart murmur, cardiac catherization reports etc. DNA extraction and sequencing was done and data was interpreted by multiple sequence alignment soft ware. Statistical data was done by SPSS 17.0. Th e mean age for controls was 3.14±1.82 years for TOF; 2.97±1.21 and for DTGA patients 1.84±2.26 years. TOF and DTGA were frequent in males. Th e study demonstrates frequency of this disease with its variation in Pakistani population. Consanguinity aff ects the rate of CHDs as it is 62% in patients and 25% in controls. Two novel mutations were found in CFC 1 gene. Th e study reveals frequency and prevalence for TOF and DTGA, their variation and association with other cardiac defects. CFC1 and its mutations may play a key role in cardiac malformation.
Biography:
K. Paul Marx have completed my MSc (Medical Biochemistry), MBA (Hospital Administration) and finally pursuing Ph.D from Osmania University. His research work includes study on Biomarkers and Molecular markers, Polymorphism studies on Malaria. He has vast experience in clinical laboratory and well trained in estimation of Serum Procalcitonin and gained experience in techniques like Flow Cytometer (ARYA –II), PCR, RT-PCR, MALDI-TOF, SDS- PAGE, chromatography, protein purification and other molecular biology techniques. He has been selected by Govt of India for Basic Science Research Fellowship Program. He has also to his credit availing travel grant from Department of Biotechnology, DBT for attending the Genomics Conference. He has 7 research papers published in different National and International Journals and now yet to communicate more papers to his credit. He has the ability to handle research problems independently and familiar with the current literature. He possesses a cheerful disposition and a cool temperament.
Abstract:
Malaria is a global health problem and its incidence is more prevalent in socio economically backward countries and developing countries like India. Gold standard microscopy for diagnosing malaria is choice for most clinicians. However among the newest biomarker, PCT has its own value in monitoring the severity of malaria and can be used for therapeutic management as well with highest diagnostic accuracy. PCT levels rise rapidly (within 6–12 hours) aft er an infectious insult with systemic consequences. Daily changes of plasma PCT levels give an indication of the course of the disease and the prognosis of the patient. Persistently elevated levels of PCT are associated with poor outcome and are now viewed as a failure of therapy or the lack of appropriate clearance of source of the infection. In the present investigation PCT was quantitatively analyzed along with conventional hematology and biochemical parameters and response to treatment was validated by PCT measurement in consecutive samples of both uncomplicated and severe malaria. Many studies have demonstrated that SNP’s in genes may not only aff ect the expression or activities of the enzymes or proteins but are associated with the risk of diff erent types of malaria. Since PCT is a product of CALC1 gene, we analysed CALC 1 -624T/C promoter polymorphism in malaria to disentangle their role with PCT as a marker for enhanced disease severity. Our fi ndings indicate that PCT in plasma of malaria patients positively correlated with platelet count, WBC, Neutrophil (p value 0.001). We have found strong association between serum PCT levels and neutrophil toxic granules and their usefulness as surrogate biomarkers in the management of malaria patients. In conclusion, our fi ndings indicate that persistently increased levels of PCT were always indicative of an unfavourable outcome and hidden parasitemia. Initial high levels of PCT were indicative of a more severe disease status (parasitemia, P value <0.001) and this refl ected in a longer patient stay predicting adverse outcomes. From our observations it can also be concluded that -624T/C polymorphism may be related to higher risk of malaria in Indian population. So in current scenario, addition of various and reliable biomarkers to the standard work-up of patients with good publicity could increase diagnostic certainty and improve patient’s management by administering proper therapies to the right patient at the right time thus guarantying full recovery, post hospital discharge.
Gehan Hamdy
Cairo University, Egypt
Title: Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients
Biography:
Gehan Hamdy has completed here MBBCh from Kasr El Ani Hospital, Cairo University, Egypt and Postdoctoral studies from same University. She is Assistant Professor of Internal Medicine. She has published more than 10 papers and 3 case reports in reputed journals.
Abstract:
Background: Th e identifi cation of additional genetic risk factor is an on-going process that will aid in the understanding of Rheumatoid Arthritis (RA) aetiology. A genome-wide association scan in Crohn’s Disease (CD) highlighted the Interleukin-23 Receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesized that IL23R could be a shared susceptibility gene. Th e rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyze IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients. Methods: A group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the fi rst SNP and restriction fragment length polymorphism/PCR (RFLP/ PCR) in the last two SNPs. Results: Our data emphasise that the AA genotype of rs11209026 (Arg381Gln) was signifi cantly associated with RA patients compared to the controls (p value=0.001). We did not fi nd any signifi cant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (p value=1.000 & 0.562, respectively). Conclusion: Our results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the sub-group of patients who will benefi t from the selective suppression of the IL23 signaling which would represent new perspectives toward a personalized therapy of RA patients by further studies.