Day 2 :
Keynote Forum
Martin Falk
Czech Academy of Sciences, Czech Republic
Keynote: Chromatin structure and chromosomal rearrangements in CD34+ cells and lymphocytes from Myelodysplastic syndromes (MDS) patients
Time : 9:00-9:45
Biography:
Martin Falk is the Head of the Department of Cell Biology and Radiobiology at the Institute of Biophysics, Czech Academy of Sciences, Czech Republic. He has completed his PhD in Molecular Biology and Genetics from Masaryk University in 2004. He has published over 30 papers with about 500 citations, given 26 invited lectures at international conferences and has been serving as an Editorial Board Member of several repute journals. In 2009, he has been awarded the Premium of Otto Wichterle devoted by the Czech Academy of Sciences to outstanding young scientists. His research interests include radiobiology and cancer biology.
Abstract:
MDS syndrome (MDS) refers to a heterogeneous group of clonal hematologic disorders characterized by inefficient hematopoiesis. Incidence of MDS is 4 cases per 100000 people. The most typical cytogenetic abnormality with still unknown reasons is a partial or complete deletion of 5q. By combining 3D-fluorescence in situ hybridization with BAC probes and high-resolution confocal microscopy on isolated lymphocytes and CD34+ hematopoietic cells from healthy donors and MDS patients, we reconstructed higher-order nuclear organization of the CDR (common deleted region) located between bands 5q31 and 5q32. Radial and mutual positions of BAC probes, specific for individual chromosomal bands in CDR were determined and suggest that chromatin in this locus forms a giant higher-order loop that is attached to the nuclear envelope by its base. Secession of this loop could explain large deletions in CDR and suggests that higher-order chromatin structure contributes to formation of 5q deletions associated with MDS. Though the mechanisms responsible for the loop secession remain to be revealed, our findings show that 'structuromics' should be taken into consideration (together with genomics, metabolomics, etc.) when we try to explain pathogenesis of some diseases.
- Micro RNA| Clinical Genomics| mRNA Analysis | Next Generation Sequencing | Comparative Genomics| Genome Engineering | Functional Genomics | Microbial Genomics
Location: Golden Tulip Berlin - Hotel Hamburg
Chair
Janos Zempleni
University of Nebraska-Lincoln, USA
Co-Chair
Martin Falk
Czech Academy of Sciences, Czech Republic
Session Introduction
Janos Zempleni
University of Nebraska-Lincoln, USA
Title: Delivery of functional RNA cargos by dietary exosomes from cow’s milk in C57BL/6J mice
Time : 9:45-10:15
Biography:
Janos Zempleni has obtained his PhD in Nutrition Science from the University of Giessen, Germany and received Postdoctoral training at Innsbruck University Medical School, Austria, Emory University School of Medicine, USA and the University of Arkansas for Medical Sciences, USA. He is the Willa Cather Professor of Molecular Nutrition at the University of Nebraska-Lincoln, USA, where he directs an NIH-funded obesity prevention and nutrient signaling center. He has published more than 200 papers and has been continuously funded by federal agencies and foundations for 15 years and is a Fellow of the American Association for the Advancement of Sciences.
Abstract:
Various species of RNA, including microRNAs and mRNAs are encapsulated in exosomes from dietary sources, including cow’s milk. Encapsulation confers protection against degradation and provides a vehicle for intestinal uptake of exosomes and their RNA cargos by endocytosis. In previous studies we challenged the paradigm that microRNAs and mRNAs are derived solely from endogenous sources. We demonstrated that milk consumption causes a postprandial increase in plasma microRNAs (including bovine-specific microRNAs), endogenous microRNA synthesis is insufficient to compensate for dietary microRNA depletion and dietary microRNA are delivered to circulating cells and tissues to regulate gene expression in host organisms. Here we assessed the bioavailability and distribution of milk exosomes endogenously and exogenously labeled with fluorophores, phenotypes of exosome depletion and the functionality of milk exosome cargos in wild-type and transgenic mice. Dose-response studies of milk exosomes were conducted using a live mouse imaging system. Our data suggest that mice absorb milk exosomes and that a fraction of these exosomes escapes re-packaging in the intestinal mucosa and reaches tissues in intact form; the majority of exosomes accumulates in macrophages. Exosome feeding studies suggest that dietary depletion elicits a substantial decrease in fertility, intrauterine growth and postnatal survival; Exosome depletion also caused aberrant purine metabolism. Ongoing studies suggest that dietary exosomes extend the life span of tamoxifen-inducible Drosha conditional knockout mice and that mRNA cargo in milk exosomes can be translated into proteins.
Maria C Ovejero-Benito
Instituto de Investigación Sanitaria la Princesa, Spain
Title: Polymorphisms that regulate the response to Etanercept in psoriatic patients
Time : 10:15-10:45
Biography:
Maria Carmen Ovejero-Benito has completed her PhD in 2013 from the Universidad Autonoma de Madrid. Since 2004, she is collaborated in cutting edge projects in areas of cancer, chemistry, neurodegeneration, neurogenesis and epigenetics. She has performed research in institutions such as Cajal Institute, NYU, Universidad de Valencia, LGC, UK and the Spanish Research Council. Her scientific results have been recognized by 6 publications in high-impact factor journals and through 3 presentations and 6 posters in scientific meetings. Currently she carries out projects in Pharmacogenetics in Dr. Abad Lab in Instituto de Investigación Sanitaria la Princesa.
Abstract:
Etanercept is an anti-TNF biologic drug effective for moderate-to-severe psoriasis. However, 30% of the patients do not respond to this drug. In this study, the association between 121 polymorphisms with the response to etanercept was evaluated in patients with moderate-to-severe plaque psoriasis. The results of the multivariate analysis showed an association between polymorphisms rs13437088 (HLAB/MICA), rs96844 (MAP3K1), rs2431697 (PTTG1), rs9304742 (ZNF816A) and the response to etanercept treatment. PASI75 at 3 months of treatment with this drug was used as an efficacy measure. The association between the polymorphisms in the MAP3K1 and ZNF816A genes and the response to anti-TNF drugs with the PASI75 at 3 months was validated in a previous study from our lab. This is the first study to show an association between these polymorphisms and the specific response to etanercept treatment in psoriasis patients. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.
Ebtesam Al-Ali
Kuwait Institute for Scientific Research, Kuwait
Title: Molecular characterizing of TYLCV in cucumber plants in Kuwait
Time : 10:45-11:15
Biography:
Ebtesam Al-Ali has obtained her BSc in 1993 from Kuwait University and worked for Kuwait University as Research Assistant, then joined KISR in 1993 and led 5 projects. She has published more than 5 papers in reputed journals and international conferences. Her field of experience is in plant virus detection, primer design, cloning and sequencing, ELISA, DNA extraction, PCR amplification, RCA-Rolling Circle Amplification, TYLCV detection on tomatoes, also trained twice in the University of Wisconsin Madison under the supervision of Professor Amy Charkowski as well as University of Washington state under supervision of Professor Hanu Pappu.
Abstract:
High scores of vegetable crop losses had been recorded in Kuwait agricultural farms, viral diseases were the main causal agent of these economic losses in many crops, mainly tomato and recently recorded on cucumber. TYLCV was reported as a major pest of tomato and cucumber but it was not characterized at the molecular level. The white-fly was main transmitter of TYLCV. Common symptoms on cucumber plants infected with TYLCV were leaf and fruit deformation, mosaicing, yellowing, upward leaf cupping, stunting. 200 samples of cucumber leaves were collected and the symptoms resulting from viral diseases were recorded and documented. DNA was extracted from 200 infected cucumber leaf samples and PCR detection was performed on 100 samples using two different primer pairs (TY1 and TY2 and TYC1R and TYC1F). PCR tests revealed that 75 samples out of 100 tested samples were positive. Best results were performed by TY1 and TY2 primer pair. Positive samples were stored for further analysis.
Chi-Tai Yeh
Taipei Medical University-Shuang Ho Hospital, Taiwan
Title: Study of expression and functional mechanisms of histamine N-MethylTransferase (HNMT) in tumorigenesis and correlation with progression in lung cancer
Time : 11:30-12:00
Biography:
Chi-Tai Yeh has received his PhD in Food Science and Biotechnology from National Chung Hsing University. He is currently the Research Fellow and Executive Secretary of Department of Research of Taipei Medical University-Shuang Ho Hospital. He has contributed 2 book chapters, published 35 articles in the field of cancer & nutritional chemistry journal and got 2 patents in the medical compound of cancer therapy. His major research interests include cancer cell biology, cancer stem cell research, nutrigenomis and cancer chemoprevention with dietary phytochemicals.
Abstract:
Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the down-regulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.
Xiaoyan Jiang
University of British Colombia, Canada
Title: Identification of new microRNA biomarkers in drug-insensitive cancer stem cells in human leukemia
Time : 12:00-12:30
Biography:
Xiaoyan Jiang is a distinguished Scientist in the BC Cancer Research Centre, a Professor in the Department of Medical Genetics and an Associate Member in the Department of Medicine at the University of British Columbia, Vancouver, Canada. Her research interests are focused on basic and translational research of molecular properties of leukemic stem cells that contribute to the development of leukemia and drug resistance. She has been invited to present her work at national and international conferences (>120), to join Editorial Boards of 20 reputed journals and has published more than 100 peer-reviewed publications, review articles and book chapters.
Abstract:
ABL tyrosine kinase inhibitor (TKI) therapies have had a major impact on treatment of chronic myeloid leukemia (CML) worldwide. However, TKI monotherapies are not curative and initial and acquired TKI resistance, as well as relapse, remain challenges. To identify miRNAs in TKI-insensitive CD34+ stem/progenitor cells that might serve as potential biomarkers and/or therapeutic targets; we have used Illumina sequencing to create absolute miRNA expression profiles from treatment-naive CD34+ cells obtained at diagnosis from TKI-responders and non-responders, and normal bone marrow (NBM) as controls. DESeq analysis revealed 66 differentially expressed miRNAs between CML and NBM samples (P<0.05); and 12 between TKI-responders and non-responders. 21 differentially expressed miRNAs were confirmed in CD34+ cells from IM-responders (n=12), non-responders (n=10) and normal individuals (n=11). Importantly, significant changes in some of these miRNAs were detected in CD34+ cells from CML patients (n=65) after 3-month nilotinib (NL) treatment; 19 normalized after NL therapy, whereas 10 showed little change. We also identified differently expressed mRNAs that are predicted targets of the deregulated miRNAs, by comparing RNA-Seq data from the same CML and NBM samples. Strikingly, only 7 differentially expressed mRNAs were predicted targets of the deregulated miRNAs when comparing TKI-responders and non-responders. These miRNAs and their target genes may serve as useful biomarkers to predict clinical response of patients to TKIs and may point to novel therapeutic targets.
Chia-Yen Dai
Kaohsiung Medical University, Taiwan
Title: Dynamics of PBMC gene expression during peginterferon/ribavirin combination therapy in hepatitis C virus genotype 1b-infected patients
Time : 12:30-13:00
Biography:
Chia-Yen Dai has completed his MD and PhD from Kaohsiung Medical University, Kaohsiung, Taiwan. He is the Director of Health Management Center and Department of Occupational and Environmental Medicine, the Visiting Staff of Hepatology Division, Department of Internal Medicine, Kaohsiung Medical University Hospital. He is also a full Professor of College of Medicine, Kaohsiung Medical University. He has published more than 200 papers in reputed journals and has been serving as an Editorial Board Member of medical journals.
Abstract:
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs). This study explored the dynamic gene expression profiles of PBMCs from chronic HCV-1 patients undergoing Peginterferon/Ribavirin (PR) therapy. PBMCs were collected at baseline and on weeks 1 and 4 from 27 chronic HCV-1 patients treated with a 48-week PR regimen (screening dataset n=7; validation dataset n=20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after the completion of therapy. An Affymetrix microarray was used to identify differentially expressed genes between SVR and non-SVR patients and was validated by quantitative PCR. We found 13 genes at week 1 and 24 genes at week 4 were differentially expressed in the SVR group compared with the non-SVR group. Eight target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3 and DDX60) were selected at week 1 as the major components of a scoring method to predict the treatment outcome for HCV-1 patients. This predictive model reliably stratified the responders and non-responders at week 1 [AUC=0.89, p=0.007 for SVR; AUC=0.95, p=0.003 for complete early virologic response (cEVR)), especially among patients carrying the favorable IL28B rs8099917 TT genotype (AUC=0.89, p=0.002 for SVR; AUC=1.0, p=0.008 for cEVR. The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype. We concluded that the genetic model can be used to predict the treatment efficacy of Peginterferon/Ribavirin therapy for HCV-1 patients within one week, especially those carrying the IL28B TT genotype.
Zandisiwe Emilia Magwebu
Medical Research Council, South Africa
Title: Identification of disease causing mutations in hyperglycinemic captive bred vervet monkeys (Chlorocebus aethiops)
Time : 13:45-14:15
Biography:
Zandisiwe Emilia Magwebu is currently a PhD student of South African Medical Research Council through the University of the Western Cape in South Africa. In 2014, she was a part of the Next Generation Scientist (NGS) group at Novartis Pharma, Basel, Switzerland.
Abstract:
High levels of glycine were observed in the plasma (457-795 µmol/L, normal <350 µmol/L) and CSF (7.5-12.7 µmol/L, normal range 3-8) of a small percentage (8%) of captive bred vervet monkeys characterized with total cataract formation at Primate Unit and Delft Animal Centre. Although cataracts have been documented for a variety of primate species, hyperglycinemia as well as this rare and unusual association of conditions have not been reported in the literature before and clearly need elucidation. The purpose of this study was to investigate the disease causing genes in hyperglycinemic vervet monkeys. Eight animals were selected based on their cataract and hyperglycinemic status. The monkeys were assigned into a control and spontaneous (cataract/ hyperglycinemic) group. Gene expression and genotyping experiments were conducted using RNA and DNA samples extracted from blood. Three genes that are associated with nonketotic hyperglycinemia were prioritized, namely: Glycine dehydrogenase (GLDC), aminomethyltransferase (AMT) and Solute Carrier Family 6, Member 9 (SLC6A9). Genotyping analysis of the complete coding sequence of GLDC, AMT and SLC6A9 revealed eight novel single base substitutions of which four were non-synonymous missense and four were silent nucleotide changes. For gene expression, AMT and SLC6A9 were down-regulated in hyperglycinemic monkeys. Therefore, it is possible that GLDC, AMT and SLC6A9 genes may be responsible for hyperglycinemia in captive bred vervet monkeys.
Ali Hosseini Bereshneh
Tehran University of Medical Sciences, Iran
Title: Mutation detection of RB1 tumor suppressor gene (exon 18 & 19) and expression assay of FGF2 oncogene in patients with brain tumors including meningioma and astrocytoma
Time : 14:15-14:45
Biography:
Ali Hosseini Bereshneh has completed his Bsc in Clinical Laboratory Sciences (Medical Technology) from Mashhad University of Medical Sciences and he is currently pursuing MSc in Human Genetics, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences. He has published more than 15 national and international papers in Iranian and international journals. He has published 5 national books in the area of Medical Genetics, Genetics of Dentistry and Prenatal Diagnosis & Genetic Counseling. He is a Member of Iranian Medical Genetics Society and Medical Laboratory Society.
Abstract:
Most studies have shown that there are association between the development and malignancy of brain tumors and tumor suppressor genes and oncogenes. The aim of this project is to investigate the RB1 gene mutations in exon 18 and 19 and FGF2 oncogene expression in patients with Astrocytoma and Meningioma type’s brain tumor. This is an in vitro study in which the extraction of DNA from 20 samples of fresh brain tissue was performed by phenol-chloroform protocols. After PCR amplification of exon 18 and 19 of RB1 gene, screening by SSCP (Single-Strand Conformation Polymorphism) was performed to detect the possible shifts. Those shifts were sequenced. Then the cells were extracted from fresh brain tissue for analysis of FGF2 gene expression by flow cytometry. In this study was detected two unknown variation (Heterozygote Substitution) in intronic regions including c.1815-170T>G and c.1960+107T>G; and one insertion mutation in intronic region c.1960+108_1960+109isnT. It was observed that FGF2 gene expression in astrocytoma samples was increased. Findings from this study were indicated that mutations in RB1 gene mostly was in malignant astrocytoma brain tumor type; also, since the FGF2 gene expression in astrocytoma brain tumors was higher than benign meningioma type of brain tumors. Overexpression of FGF2 gene may play an essential role in malignant brain tumor and this may be important in diagnosis and new therapeutic methods of brain tumors treatment.
Reyhane Sadat Saeedi
Tehran University of Medical Sciences, Iran
Title: The role of chromosomal abnormalities in spontaneous abortion and chromosome analysis importance
Time : 14:45-15:15
Biography:
Reyhane Sadat Saeedi is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. She is a Member in Students' Scientific Research Center and Student Advisory Committee of Medical School of Tehran University of Medical Sciences. She has published 3 papers in reputed journals.
Abstract:
Spontaneous abortions define as a loss of pregnancy before 20 week of gestation. About 50% spontaneous abortion of first trimester of pregnancy results from chromosomal abnormalities. Understanding of these genetic causes is absolutely important in born of healthy infants and will contribute to the management of subsequent pregnancies. Fetal aneuploidy or monosomy and trisomy of fetus caused upset to the natural process of fetal development and eventually lead to miscarriage. In the most cases, these aneuploidies result from error in the disjunction of gamete chromosomes and the risk of recurrence is low. All symptoms of these disorders are due to dosage of gene expression. Enhanced maternal age increases damage to ovum and heightens the risk of miscarriage and birth defects. The importance of genetic analysis in miscarriage is evident when carrier parents of balanced rearrangement experience recurrent abortions. These parents have a normal phenotype but have susceptibility to produce unbalanced gametes that can leads to miscarriage. Due to the possibility of being parent’s carrier, chromosome analysis and risk assessment are crucial for understanding of recurrence risk. Chromosomal analysis in aborted fetuses is risk assessment of recurrent abortion in subsequent pregnancy. Actually utilization of genetic counseling and knowing the causes of abortion and genetic bases of this condition will be helpful in management of subsequent pregnancies and birth of healthy newborns. In addition, peer understanding of spontaneous abortion genetic causes could be helpful in better utilize of diagnostic and therapeutic approaches of assisted reproduction.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran
Title: Pharmacogenetics in breast cancer therapy: Patient’s genetics profile in trastuzumab and tamoxifen prescription
Time : 15:15-15:45
Biography:
Saeed Tarverdizadeh is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center. He has published 3 papers in reputed journals.
Abstract:
Breast cancer that is caused by the accumulation of genetic and epigenetic factors, is one of the main causes of death resulted from cancer. Various therapeutic ways have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show the different responses of these treatments and recurrence after those in some patients. This diversity has resulted by the difference in biological and molecular characteristics. So genomic and molecular studies became more important and the role of targeted treatment based on an individual's genome was highlighted. Today, the progress in personalized medicine using specific individual genome profile has been possible. The ultimate goal of such studies, in the setting of the personalized medicine is providing markers which can be used to risk assessment of progressing disease. This new science cause great development in the treatment of breast cancer by recognition of specific markers and application of targeted treatment like monoclonal antibodies which Trastuzumab and Tamoxifen are the most common examples. The aim of this review is to describe the different aspects of personalized medicine in the breast cancer treatment.
- posters
Location: Golden Tulip Berlin - Hotel Hamburg
Session Introduction
Qu Zhengzhong James
Genome Institute of Singapore, Singapore
Title: Development of a comprehensive high-coverage, cost effective HLA typing assay
Biography:
Qu Zhengzhong James has completed his PhD from the Chinese University of Hong Kong, Department of Chemical Pathology. He is the laboratory Manager of the POLARIS (Personalized OMIC Lattice for Advanced Research and Improving Stratification), a strategic program to pilot the application of clinical genomics in the treatment and diagnosis of medical diseases in Singapore and the region. His job responsibility is to make sure all the testing procedures in the lab will meet the requirements from Singapore Ministry of Health and also meet the guidelines from the College of American Pathologists.
Abstract:
The human leukocyte antigen (HLA) is responsible for regulation of the immune system in humans. HLA typing has important clinical significance for tissue transplantation matching, autoimmune disease-association studies and drug hypersensitivity research. However, the highly polymorphic essence of the HLA genes makes it a challenging task. Conventional methods like SSO and SSP only provide lower resolution typing results and cannot identify new alleles. High-resolution techniques like SBT required other methods for confirmation of phasing and it is time consuming. Single Molecule Real Time (SMRT) sequencing is a parallelized single molecule DNA sequencing by synthesis technology developed by Pacific Biosciences. It has long read lengths which enable unambiguous phasing of the entire HLA genes. However, the cost of the SMRT sequencing is still too high for clinical routine use. To develop clinically implementable HLA typing assay by using SMRT sequencing technology, we designed two sets of multiplex PCR primers for the HLA genes. The first assay we developed enables the HLA typing of A, B, C, DRB1, DQB1, DQA1, DPA1 and DPB1 genes for one patient by using one SMRT cell. The second assay we developed enables the typing of HLA-A genes for up to 50 patients by using one SMRT cell. Our assays provided choice of both coverage and cost-effectiveness.
Qiong Shi
Shenzhen University, China
Title: High throughput identification of novel conotoxins from cone snails by multi-transcriptomic sequencing
Biography:
Qiong Shi has completed his PhD from China Zhongshan University and Postdoctoral studies from Beijing Normal University and Japan Hokkaido University. Before joining BGI in 2011, he has worked at USA National Institutes of Health, University of Maryland and OriGene Technologies Inc. He is the Dean of BGI Academy of Marine Sciences, VP and Chief Scientist of BGI Fisheries, a Genomics Professor at University of Chinese Academy of Sciences and Shenzhen University and the Chief of Shenzhen Key Lab of Marine Genomics. He has published over 60 academic papers and 6 monographs and acquired 12 Chinese patents.
Abstract:
With an estimation of over 500 species, cone snails are classified into Conus, the biggest genus among marine invertebrates. Cone snails apply a complex cocktail of venom components to capture and digest prey. According to variation in diet, cone snails are divided into piscivorous, molluscivorous and vermivorous groups. In the past few years, our lab has successfully performed transcriptomic sequencing of around 10 species. Here, we summarize our recent data about a special species, Chinese tubular cone snail (C. betulinus), which is the dominant conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including 9 new super families. It appears that most of the identified conopeptides are synthesized in the venom duct, while a handful of conopeptides are identified only in the venom bulb and at very low levels. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for development of new pharmaceuticals and a pathway for discovery of new conotoxins.
Tianbo Jin
Xizang Minzu University, China
Title: Genetic polymorphisms of pharmacogenomic VIP variants in seven national minorities from different regions of China
Biography:
Tianbo Jin has completed his PhD from Xi’an Jiaotong University and Postdoctoral studies from Brown University, School of Medicine. He is the Deputy Director of Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region. He has dedicated to Pharmacogenomics for several years and published more than 100 papers in SCI journals.
Abstract:
Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. We genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Tibetan, Uygur, Miao, Li, Deng, Kyrgyz, Ihoba populations and compared our data with other major eleven populations from the HapMap data set, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI and YRI. We also downloaded SNP allele frequencies from the Allele Frequency Database to observe the global genetic variation distribution for these specific loci. Through statistical analysis, we found that genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, MTHFR and VKORC1 in our study populations differed widely from those in the 11 HapMap populations. Population structure and F-statistics (Fst) analysis also showed significant differences between these seven minorities and other HapMap populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan, Uygur, Miao, Li, Deng, Kyrgyz, Ihoba populations. We provide a theoretical basis for safer drug administration and individualized treatment plans for these seven populations. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China.
Chi-Un Pae
Catholic University of Korea, South Africa
Title: Genes involved in neurodevelopment, neuroplasticity and bipolar disorder: CACNA1C, CHRNA1 and MAPK1
Biography:
Chi-Un Pae has completed his PhD from Catholic University of Korea (CUMC), South Korea. He is the Principal Investigator of Depression Research Center, funded by Korean Government. He has published more than 334 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study we tested the association of several SNPs within three strong candidate genes, CACNA1C, CHRNA7 and MAPK1, with BPD. These genes are involved in monoamines-related pathways as well as in dendrites development, neuronal survival, synaptic plasticity and memory/learning. 132 subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17 and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. Significant differences in the distribution of alleles between the cases and controls where detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7 and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analysis demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. Overall, our data suggest a possible role of these three genes in BPD. Alterations of one or more common brain pathways (e.g. neurodevelopment, neuroplasticity and calcium signaling) may explain the obtained results. However, a limited sample size and the consequent risk of false positive findings should be carefully taken into consideration when evaluating these results.
Mohammad Roushanghalb
Tehran University of Medical Sciences, Iran
Title: PDCD1 single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus
Biography:
Mohammad Roshanghalb is currently a Medical Intern of Imam Khomeini Hospital Complex, Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center.
Abstract:
Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, three PDCD1 SNPs, including PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls using PCR-RFLP method. The PD-1.1 A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%, p=0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%, p=0.021). The other PDCD1 SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C) nor for the GGC haplotype (PD-1.1 G, PD-1.3 G, PD-1.9 C). Our findings support the influence of the PD1.1 A SNP on the development of JSLE in Iranian population.
Reyhane Sadat Saeedi
Tehran University of Medical Sciences, Iran
Title: Recent progression in hemophilia gene therapy
Biography:
Reyhane Sadat Saeedi is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. She is a Member in Students' Scientific Research Center and Student Advisory Committee of Medical School of Tehran University of Medical Sciences. She has published 3 papers in reputed journals.
Abstract:
Hemophilia is a bleeding disorder in which coagulation is corrupted. There are different types of Hemophilia, more than 400,000 people around the world living with the disease. Two common types of hemophilia are A and B, defects in coagulation factors 8 and 9 respectively. Hemophilia A is 80-85% of cases. Coagulation factors 8 and 9 located at the long arm of chromosome X and mutations in these genes result in the defective production of coagulation factors. Hemophilia considered an appropriate target for gene therapy, because production of 1% of normal level could adjust the phenotypic problems. Various methods have been developed for hemophilia gene therapy, producing coagulation factors in the patients ultimately. Injection of coagulation factor gene by vector into the stem cells extracted from the patients or vectors containing the transgene insertion into differentiated cells with long survival, such as muscle cells and liver are among the most important of these methods. As well as the most recent methods of gene therapy, gene transfer based on induced pluripotent stem cells is abbreviated iPS. Hepatocytes a very suitable target cells for hemophilia gene therapy because these cells are the main site of synthesis of coagulation factors. Muscle cells also are suitable for the injection of transgenes in gene therapy for hemophilia because of its appropriate secretory power and its availability. The most important and most widely used viral vectors for gene therapy of hemophilia are retroviral vectors and lentiviral and Adeno-associated viruses.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran
Title: Autosomal recessive non syndromic hearing loss (ARNSH): Different mutations spectrum in Iran
Biography:
Saeed Tarverdizadeh is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center. He has published 3 papers in reputed journals.
Abstract:
Sensorineural hearing loss is the most common disorder in humans that heterogeneity is high, and one out of every 1,000 to 2,000 newborns, affected by sensorineural hearing loss. More than 50 percent of the causes of deafness have been attributed to genetic factors. Non-syndromic hearing loss include more than 70 percent of cases of hereditary deafness; which 85% of NSHL have autosomal recessive hereditary pattern. So far, more than 100 loci for this type of hearing loss are estimated. Nuclear and mitochondrial gene mutations can cause this disease. Of which DFNB1 locus is responsible for half of recessive deafness; including transfer protein genes and ion channel protein like connexin 26 and 30. In Iran, this locus is a primary cause of hearing loss. GJB2 mutations especially 35del G play important role in developing hearing loss in Iran. After that, mutations in SLC26A4 gene in DFNB4 locus are the second cause of ARNSH in our country. The next locus to study could be DFNB59 that contains PJVK gene and it is highly prevalent in Iran. Also mutations in mitochondrial genes such as 12S rRNA genes are involved in development of pre lingual non-syndromic hearing loss.