Day :
- Human Genetics | Cancer Genetics | Genetic Disorders | Molecular and Cellular Genetics | Medical Genetics | Population and Evolutionary Genetics | Cytogenetics | Epigenetics | Immunogenetics | Pharmacogenomics | Microbial Genomics | Cancer Genomics | Functional Genomics | Nutrigenomics
Session Introduction
Khushnooda Ramzan
King Faisal Specialist Hospital and Research Centre, Saudi Arabia
Title: Challenges and rewards of Usher syndrome genetics research in Saudi Arabia
Time : 13:50-14:15
Biography:
Khushnooda Ramzan, PhD in molecular biology works as Scientist in the Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh. She got her PhD from the Punjab University; during which she discovered new genes for hearing loss. After her PhD she joined the department of genetics at KFSHRC, and continued working mainly on the genetics of deafness in the Saudi population. Her research focus was to investigate the role of different genes in hearing loss within the Saudi families. So far, she has characterized and documented genetic basis of deafness in more than 500 families of Saudi Arabian origin; their incidence and distribution were also documented..
Abstract:
Hearing loss is one of the most common sensory disorders in humans with both genetic and environmental etiologies. Usher syndrome (USH) is the most common cause of combined deafness and blindness inherited in an autosomal recessive mode. Molecular diagnosis is of great significance in revealing the molecular pathogenesis and aiding the clinical diagnosis of this disease. However, the molecular diagnosis remains a challenge due to the phenotypic and genetic heterogeneity in USH. Our study aims to comprehensively delineate the genetic basis of this disorder in Saudi Arabia. Consanguineous families are a powerful resource for genetic linkage studies/homozygosity mapping for recessively inherited hearing impairment. Prioritized linkage analysis and homozygosity mapping were conducted. A next-generation sequencing-based multiplexing assay that encompasses the 120 known hearing loss genes was also used. For genes involved in Usher syndrome, we found a mutation in MYO7A (42 families), CDH23 (5 families), PCDH15 (4 families), USH1G (1 family), USH1C (1 family) and USH2A (2 families). The overall results of this study are highly suggestive that the underlying molecular basis of hearing loss in Saudi Arabia is very genetically heterogeneous. The benefit of this study will hopefully provide the foundation for knowledge and awareness through screening of carrier status and genetic counseling, thereby having a major impact upon early intervention for and prevention of Usher syndrome in our population.
Change L Tan
University of Missouri, USA
Title: Holistic studies of whole genomes
Time : 11:50-12:15
Biography:
Change Tan received a BS in Chemistry at Hunan Normal University, an MS in organic chemistry at Nan Kai University, a PhD in biochemistry at University of Pennsylvania and a postdoc training in genetics at Harvard Medical School. She joined University of Missouri in 2005 and is currently an associate professor in the Division of Biological Sciences at University of Missouri. Her research interests include genetics, comparative genomics, developmental biology, molecular biology, origin of life, and origin of biodiversity. She teaches molecular biology and signal transduction to graduate and undergraduate students.
Abstract:
Statement of the Problem: Two complementary goals of biological research are to understand how each organism works and how that relates to other organisms. Specifically, the function of all genes and non-genes (i.e., all the regions of a genome that do not code for any genes) of each organism and how its genes and non-genes compare with those of other organisms. The progress in DNA sequencing has generated large amounts of sequence data, and many computer programs have been developed to interpret these data, especially in identifying and analyzing the similarities among genes and genomes. Unfortunately, in the zeal of finding similarities, the differences among genes and genomes are often not just simply ignored, but intentionally masked, trimmed, or filtered. With the increase in the number of genes or organisms being compared, the deleted data increase exponentially. The tragic consequence is that the very data we need to answer a question such as “what makes a dog a dog, instead of a cat” are cut out, because much of our hard-generated data have been rendered invisible. Methodology & Theoretical Orientation: I propose to use a holistic approach to address the problem; using all the data, all the sequence of whole genes, all the genes of whole genomes. Instead of cherry-picking only those regions of genomes that are similar enough to be aligned, carefully inspect each section. Conclusion & Significance: Many a time, the very life of an organism hinges on a small part of its genome, even a single base pair as shown by the identification of many lethal point-mutations. Ignoring "irrelevant" data, however benign it may appear, can be devastating. It is foreseeable that a tremendous amount of knowledge can be gained by comparing and contrasting different life forms using both similar and different sequences of genes and genomes.
Sadia Ajaz
University of Karachi, Pakistan
Title: Germ-line mutanome profiling of the Breast cancers in Pakistani population
Time : 12:15-12:40
Biography:
Sadia Ajaz is currently involved in molecular profiling of breast cancers in local population. The translational medicine approach integrates molecular epidemiology of breast cancers with molecular pathology and molecular cancer therapeutics. The research studies are designed according to epidemiological principles and investigate the applications of molecular discoveries in prevention and management of cancers in general and breast cancers in particular. She has eleven publications so far, including seven publications in the field of molecular oncology in peer-reviewed international journals. Her research experience includes molecular oncology projects at prestigious national and international institutions. Area(s) of Research: Biochemistry, Human Genetics and Molecular Medicine.
Abstract:
Statement of the Problem: Cancers are complex disorders. Consanguineous populations, by virtue of autozygosity, provide a unique model for the investigations of the underlying genetic component(s). A prototype example in the breast cancers is the identification of BRCA1/2 gene defects in Ashkenazi Jews. In Pakistan, the age-standardized rate (ASR) of the incidence of breast cancers in females is among the highest in Asia, whereas the mortality rate is one of the highest in the world. With the consanguinity rate of 56.4% and inbreeding coefficient (F) of 0.0331, it is extremely important to investigate the role of inherited mutations in breast cancers in Pakistani population. Methodology and Theoretical Orientation: BROCA analysis for breast cancers consists of twenty-seven (27) established and candidate breast cancer genes involved in molecular carcinogenesis. A pilot hospital-based cohort study was designed. Eighty-five breast cancer patients and three controls with no medical history of any cancer participated in the study. The BROCA investigations were carried out by a genomic capture, massively parallel next-generation sequencing assay on Illumina HiSeq2000 assay with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. After informed consent, the mutations were screened in the familial samples. Findings: The analysis revealed germ-line mutations in 12% of the patients. These mutations were restricted to three genes (BRCA 1, BRCA 2, and TP53). The identified mutations consist of both novel and previously reported alterations and result in protein truncation. No mutations were identified in the remaining twenty-four (24) genes. Mutation screening in the familial samples identified carriers in four out of five families. Conclusions and Significance: The study provides a framework for the development of preventive and treatment strategies against breast cancers in Pakistani population.
Reina Villareal
Bayer college of Medicine, USA
Title: Musculoskeletal response to hormonal therapies is influenced by CYP19A1
Time : 13:40-14:05
Biography:
Villareal has established herself as a respected patient-oriented researcher studying the genetic determinants of estrogen metabolism and bone biology. She obtained RO3, R21, and VA Merit Award support for her research program. She left Washington University to become an Associate Professor of Medicine at the New Mexico VA Health Care System and the University of New Mexico School of Medicine. There, she served as the Chief of the Endocrinology Division. Recently, she joined the faculty at Baylor Medical College of Medicine as an Associate Professor of Medicine. She has a VA Merit Award to support work on the role of sex steroids to augment lifestyle in obese, elderly patients.
Abstract:
Polymorphisms of the CYP191A1 which encodes aromatase, the enzyme that converts testosterone to estradiol, are reported to influence the skeletal phenotypes in both men and postmenopausal women. We reported that the rs700518 polymorphism (G to A) of the CYP19A1 was associated with differences in bone loss and body composition changes among women with estrogen receptor positive breast cancer given aromatase inhibitors (AIs). Women with the AA genotype had significant bone loss in the spine and total hip compared to women with the G allele (GA+GG genotypes) after 1-year AI treatment. Meanwhile, women with the GG genotype had significant loss in fat-free mass (FFM) and gain in trunk fat mass (TFM) compared to women with the A allele (AA+GA) who had no loss in FFM but had significant loss in TFM. These findings suggest that women with the GA genotype have the best side effect profile to AIs. Using the same concept in hypogonadal men treated with testosterone for 18 months shows that although there were no inter-genotype differences in bone mineral density changes (hip and spine) for both rs700518 and rs1062033, the GG genotype (G to C) for rs1062033 experienced significant improvement in bone geometry parameters (total bone and cortical area) compared to GC+CC genotypes. Moreover, total fat and TFM decreased more in AA than GA+GG and in CC than GC+GG in rs700518 and rs1062033, respectively. Lean mass increased more in AA than GA+GG and in CC than GC+GG in rs700518 and rs1062033, respectively. We found no intergenotype differences in adverse effects on the hematocrit and the prostate. A difference in CYP19A1 expression in the fat was observed in rs1062033 variants. Rs700518 and rs1062033 are in partial linkage in our sample. Thus, we conclude that CYP19A1 polymorphisms influences response to hormonal therapies and should be considered in treatment decision-making.
Reina Villareal
Bayer college of Medicine, USA
Title: Musculoskeletal response to hormonal therapies is influenced by CYP19A1
Biography:
Villareal has established herself as a respected patient-oriented researcher studying the genetic determinants of estrogen metabolism and bone biology. She obtained RO3, R21, and VA Merit Award support for her research program. She left Washington University to become an Associate Professor of Medicine at the New Mexico VA Health Care System and the University of New Mexico School of Medicine. There, she served as the Chief of the Endocrinology Division. Recently, she joined the faculty at Baylor Medical College of Medicine as an Associate Professor of Medicine. She has a VA Merit Award to support work on the role of sex steroids to augment lifestyle in obese, elderly patients.
Abstract:
Polymorphisms of the CYP191A1 which encodes aromatase, the enzyme that converts testosterone to estradiol, are reported to influence the skeletal phenotypes in both men and postmenopausal women. We reported that the rs700518 polymorphism (G to A) of the CYP19A1 was associated with differences in bone loss and body composition changes among women with estrogen receptor positive breast cancer given aromatase inhibitors (AIs). Women with the AA genotype had significant bone loss in the spine and total hip compared to women with the G allele (GA+GG genotypes) after 1-year AI treatment. Meanwhile, women with the GG genotype had significant loss in fat-free mass (FFM) and gain in trunk fat mass (TFM) compared to women with the A allele (AA+GA) who had no loss in FFM but had significant loss in TFM. These findings suggest that women with the GA genotype have the best side effect profile to AIs. Using the same concept in hypogonadal men treated with testosterone for 18 months shows that although there were no inter-genotype differences in bone mineral density changes (hip and spine) for both rs700518 and rs1062033, the GG genotype (G to C) for rs1062033 experienced significant improvement in bone geometry parameters (total bone and cortical area) compared to GC+CC genotypes. Moreover, total fat and TFM decreased more in AA than GA+GG and in CC than GC+GG in rs700518 and rs1062033, respectively. Lean mass increased more in AA than GA+GG and in CC than GC+GG in rs700518 and rs1062033, respectively. We found no intergenotype differences in adverse effects on the hematocrit and the prostate. A difference in CYP19A1 expression in the fat was observed in rs1062033 variants. Rs700518 and rs1062033 are in partial linkage in our sample. Thus, we conclude that CYP19A1 polymorphisms influences response to hormonal therapies and should be considered in treatment decision-making.
Diptee A. Kulkarni
Glaxo Smith Kline Research and Development, USA
Title: Identification of novel cancer target genes by combining data from the cancer genome wide association studies (GWAS), regulatory DNA elements and The Cancer Genome Atlas (TCGA)
Time : 14:05-14:30
Biography:
Diptee Kulkarni is an experienced pharmaceutical R&D professional with expertise in cancer genetics and genomics, cancer molecular biology, pharmacogenetics, and precision medicine. She’s a licensed physician with a PhD in cancer molecular pharmacology. She has extensive experience in understanding the genetic basis of cancer risk and outcomes as well as drug response genetics. Her current work focuses on using genetic information for effective drug discovery and development for which she utilizes data from publicly available genetic/genomic databases as well as genetic/healthcare data obtained from the real world setting such as biobanks.
Abstract:
Numerous genome-wide association studies (GWAS) have identified robust associations between germline singlenucleotide polymorphisms (SNPs), many in the non-coding genome, and cancer. There is evidence for the non-coding SNP associations to be enriched in regulatory regions of the genome such as enhancers and promoters – for example, the LMO1 super enhancer SNP in neuroblastoma (Oldridge et al., 2015) or GREM1 enhancer SNP in colorectal cancer (Lewis et al., 2014) among others. These SNPs were shown to regulate expression of LMO1 and GREM1, respectively, through differential transcription factor binding and in turn oncogenic dependency in tumor cells. To identify additional examples of regulatory SNPs as cancer drivers, we overlaid published genome-wide significant cancer associations with active chromatin marks from Encyclopedia of DNA Elements and searched for SNPs that resided within gene regulatory elements. To map these SNPs to candidate genes and determine direction of effect, we co-localized GWAS signals with expression quantitative trait (eQTL) signals from the Genotype-Tissue Expression (GTEx) Consortium database. Lastly, we looked for somatic gene amplification and/or overexpression of the mapped genes in the Cancer Genome Atlas (TCGA). With this approach, we identified a set of target genes that not only exhibit significant cancer association in GWAS, but also have evidence for epigenetic regulation and propensity for amplification and/or overexpression in tumors. We identified more than 25 novel cancer-target pairs with strong germline, regulatory and somatic gain of function evidence. A look up through synthetic lethality screen data available inhouse suggested that several of these targets are self-lethal, further underscoring their importance for cancer cell proliferation and survival.
Anna R Moore
Temple University Philadelphia, USA
Title: Molecular regulation of experience dependent plasticity
Time : 14:30-14:55
Biography:
Anna Moore is a Assistant professor in the department of biology at Temple University, Philadelphia,USA. She has a long standing interest in understanding how the brain develops and adapts to the world around it. She was trained as an electrophysiologist during her PhD where she explored the emergence of electrical activity in cortical neurons during development. For her postdoctoral work, she went on to expand her skill set to include molecular biology, mouse genetics, and calcium imaging to identify novel molecules important for synapse formation.
Abstract:
Sensory experience plays an important role in shaping neural circuitry through activity-dependent regulation of both synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Using the mouse visual system as a model, we investigated the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in ocular dominance plasticity. Our in vivo analysis reveals that a primary function of Rem2 signaling is to stabilize the intrinsic excitability of cortical neurons in order to maintain proper levels of network activity. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rate in the absence of Rem2. In addition, our data establish a novel, cell-autonomous role for Rem2 in regulation intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Taken together, we propose that Rem2 functions as a calcium-sensitive cytoplasmic signal transduction molecule and works to convey changes at the membrane into changes in gene expression in the nucleus to regulate intrinsic excitability. Our molecular studies promise to yield significant insight into the transcriptional program by which a neuron instructs its intrinsic properties.
Biography:
Change Tan received a BS in Chemistry at Hunan Normal University, an MS in organic chemistry at Nan Kai University, a PhD in biochemistry at University of Pennsylvania and a postdoc training in genetics at Harvard Medical School. She joined University of Missouri in 2005 and is currently an associate professor in the Division of Biological Sciences at University of Missouri. Her research interests include genetics, comparative genomics, developmental biology, molecular biology, origin of life, and origin of biodiversity. She teaches molecular biology and signal transduction to graduate and undergraduate students.
Abstract:
Statement of the Problem: Two complementary goals of biological research are to understand how each organism works and how that relates to other organisms. Specifically, the function of all genes and non-genes (i.e., all the regions of a genome that do not code for any genes) of each organism and how its genes and non-genes compare with those of other organisms. The progress in DNA sequencing has generated large amounts of sequence data, and many computer programs have been developed to interpret these data, especially in identifying and analyzing the similarities among genes and genomes. Unfortunately, in the zeal of finding similarities, the differences among genes and genomes are often not just simply ignored, but intentionally masked, trimmed, or filtered. With the increase in the number of genes or organisms being compared, the deleted data increase exponentially. The tragic consequence is that the very data we need to answer a question such as “what makes a dog a dog, instead of a cat” are cut out, because much of our hard-generated data have been rendered invisible. Methodology & Theoretical Orientation: I propose to use a holistic approach to address the problem; using all the data, all the sequence of whole genes, all the genes of whole genomes. Instead of cherry-picking only those regions of genomes that are similar enough to be aligned, carefully inspect each section. Conclusion & Significance: Many a time, the very life of an organism hinges on a small part of its genome, even a single base pair as shown by the identification of many lethal point-mutations. Ignoring "irrelevant" data, however benign it may appear, can be devastating. It is foreseeable that a tremendous amount of knowledge can be gained by comparing and contrasting different life forms using both similar and different sequences of genes and genomes.
- Poster presentations
Session Introduction
Adriana Pérez Portilla
National Centre for Biotechnology, Spain. Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Spain
Title: Characterization of Genetic variation in the Fc gamma receptor locus in the Ecuadorian population
Biography:
Adriana Pérez Portilla studied Biochemistry and Pharmacy at the University of Cuenca (Ecuador). She has a Master´s degree in Biotechnology at the Technical University of Madrid (UPM), and she is in a PhD program in Molecular Biosciences at the Autonomous University of Madrid (UAM).
Abstract:
Human Fcγ receptors (FcγRs) are glycoproteins that bind the Fc region of IgG. These proteins are essentially receptors for immune complexes and are primarily, though not exclusively, expressed on cells of the innate immune system, thereby linking the humoral immune system with cellular effectors. Based on their structure and affinity for monomeric IgG three classes of FcγRs are distinguished, FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16). Low-affinity FcγRs (CD32 and CD16) are encoded in a single FCGR locus on chromosome 1, a region characterized by both genetic polymorphism and copy number variation (CNV). The combination of gene duplication, multiple common single nucleotide polymorphisms (SNPs) and CNVs is characteristic of regions involved in immune regulation and studies of this CNV and these SNPs in different human populations can provide insight into the evolution of this locus. We studied FCGR genetic variation in a cohort of 69 individuals of Ecuadorian origin, using both a multiplex ligation-dependent probe amplification (MLPA) method (MRC-Holland, Amsterdam, The Netherlands) and direct sequencing. In line with previously published data analyzing other South American populations, we observed a high frequency of individuals carrying 3 copies of FCGR3B (coding for a CD16B receptor) and the great majority of the currently studied donors were of the FCGR3B HNA1a allotype, which is found more frequently in South American populations than in Caucasoids. In contrast, the common FCGR2A R131H, FCGR3A V158F, FCGR2B I232T and FCGR2C Q57X polymorphisms were found in distributions similar to those observed in Caucasoids. We also identified 4 intronic SNPs in the FCGR3A gene, two of them not previously described, that might affect splicing. The implications of these data will be discussed.
Sharareh Kamfar
Hamadan University, Iran. National Institute for Genetic Engineering and Biotechnology, Iran and Baqiyatallah El - Azam Subspeciality Hospital, Iran
Title: Mitochondrial DNA copy number variation in Iranian patients with non-alcoholic fatty liver disease
Biography:
Sharareh Kamfar has graduated in molecular medicine in Hamadan University of Medical Sciences, Iran. Her thesis is about the relation between nonalcoholic fatty liver disease and mitochondria. In the future, she wants to follow this topic to get acceptable results but now she is working on Thiamine-responsive megaloblastic anemia syndrome seriously in a Pediatric Congenital Hematologic Disorders Research Center (PCHDRC). She has also researched into probiotics for many years in university..
sharareh
Abstract:
Introduction: Non-alcoholic fatty liver disease (NAFLD) is the term for a range of damages, from very mild hepatic steatosis to nonalcoholic steatohepatitis (NASH). Mitochondria are the main source of reactive oxygen species (ROS) in hepatocytes. Recent evidence suggests that mitochondrial dysfunction leads to an overproduction of ROS which is considered to be an important factor associated with progression of NAFLD. The aim of this study is to assess an association between mtDNA copy number and risk of NAFLD in a sample of Iranian population. Methodology & Theoretical Orientation: This study included 43 patients with NAFLD and 43 healthy control subjects. The mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood samples. Findings: The relative expression of mtDNA copy number was 8.4 fold higher in patients with NAFLD than healthy controls (P<0.001). In addition, the mtDNA copy number was 8.7 (P<0.001) and 8.1-fold (P<0.001) higher in nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) patients than healthy controls, respectively. Conclusion & Significance: This study showed an association between mtDNA copy number in Peripheral Blood and risk of NAFLD that may be a consequence of compensatory response to the exposures to oxidative damage induced by ROS. Therefore this results suggest that changes in mtDNA copy number may be useful as a blood-based biomarker for detection of NAFLD.
Kambiz Hasrak
Baqiyatallah El - Azam Hospital, Iran
Title: Analysis of mitochondrial DNA D-loop region mutations in Iranian patients with non-alcoholic fatty liver disease
Biography:
Kambiz Hasrak has graduated from Hamadan University of Medical Sciences, Iran in the field of molecular medicine (PhD). His thesis was about Investigation of primary or secondary origin of mitochondrial DNA variations in Colon cancer patients. Now, he is working on cancers and genetic diseases and also Thiamine-responsive megaloblastic anemia syndrome in a Molecular Genetics Laboratory in Baqiyatallah El-Azam Hospital in Tehran.
Abstract:
Introduction: Non-alcoholic fatty liver disease (NAFLD), is the term for a range of conditions caused by excessive lipid accumulation in hepatocytes in the absence of excess alcohol intake or other pathological causes. NAFLD is now the most common liver disease in the world. Mitochondria are the main source of cellular reactive oxygen species (ROS) in cells and also play a key role in fatty acid ß-oxidation and oxidative phosphorylation and therefore mitochondrial dysfunction will lead to accumulation of free fatty acids. Generated mutations by ROS in the mitochondrial DNA D-loop region could disturb mitochondrial function, oxidative phosphorylation & ATP production. Therefore these data strongly suggest that NAFLD might be a mitochondrial disease. The aim of this study was to the analysis of mutations in the mitochondrial DNA D-loop region in NAFLD patients. Methodology & Theoretical Orientation: Genomic DNA was extracted from fresh liver tissue samples of NAFLD patients and control subjects by using a DNA isolation kit. Two pairs of primers designed for PCR amplification to amplify the mtDNA D-loop region and subsequently were sequenced using a sequence analyzer. The results of the sequencing were confirmed with a human mitochondrial database which mtDNA mutations have been reported in a spectrum of clinical disorders. Findings: After D-loop sequencing, 85 different variations including 3 deletions, 6 insertions and 76 single nucleotide polymorphisms (SNPs) were detected. A significant difference was seen between two groups in 6 variations (P<0.05; T334C, C16111T, A16220C, C16266T, c16221ins, A248del). A novel insertion (16221 ins C) was observed in patients. Conclusion & Significance: we think that the disease has damaged the mitochondrial DNA and these mutations have been created. Our findings indicate that D-loop alterations are frequent in NAFLD patients and may play a significant role in the progression of NAFLD.
Guangying Wang
Chinese Academy of Sciences, China Zhejiang Gongshang University, China
Title: Toxicogenomic investigation of Tetrahymena thermophila exposed to organic pollutants and arsenic
Biography:
Wang have been well trained in bioinformatics and population genetics. Wang research interests focus on some basic questions using Tetrahymena thermophila as a model system. Based on professional skills in Bioinformatics and omics data analysis, he have made a direct contribution to reveal some important biological process or pathway in Tetrahymena and other ciliated protozoa through genome or transcriptome sequencing. Wang early publications have revealed that germline-limited sequences in Tetrahymena can encode genes with specific expression patterns and development-related functions during Tetrahymena MAC development. Wang also helps to demonstrate a facultative pathogen ciliate, Pseudocohnilembus persalinus, may gain its virulence through horizontal gene transfer. In addition, by integrating different kinds of omics data,and he helps to construct functional genomics database of Tetrahymena.
Abstract:
The organic pollutants such as Benzopyrene (BaP), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are persistent in the environment and capable of endocrine disruption within the reproductive system, the central nervous system, or the immune system. Arsenic contamination is also a serious risk to human health and affects millions of people across the world. The ciliate protozoan Tetrahymena thermophila has long been used a good unicellular eukaryotic model for toxicological studies. In this study, this organism was exposed to BaP, DDT, TBT, TCDD, and Arsenic for 24 hrs, respectively and then RNA-Seq of each toxicant exposure was performed to identify differentially expressed genes (DEGs). The functions of these DEGs were categorized using Gene Ontology enrichment analysis and the results suggested that the responses of T. thermophila were similar to those of multicellular organisms. For each toxicant, the involved gene-interaction network was construct and the model of each toxicant effect on T. thermophila was inferred. In addition, based on analysis of the networks, key enzymes that are potentially responsive to the toxicant metabolism were also identified. Functional validation of these key enzymes is ongoing.
Gulmira Yermakhanova
Medical Center Hospital of President’s Affairs Administration, Republic of Kazakhstan
Title: Study of association of some gene polymorphisms with metabolic syndrome and its components in Kazakh population
Biography:
Gulmira Yermakhanova is from Kazakhstan that is developing and an independent country in Central Asia. Her undergraduate degree is Medical care and Master’s degree in Public Health, which was completed in Kazakhstan. Currently, she works as a head of the clinical trials sector at the Medical Center Hospital of President’s Affairs Administration of the Republic of Kazakhstan. And, she is involved in the project “Study of the genetic risk characteristics of diseases associated with metabolic syndrome in Kazakh population”. Her research interests are metabolic syndrome, age-associated diseases, gerontology, and public health.
Abstract:
Purpose of the study: To assess the statistical association of gene polymorphisms with metabolic syndrome (MS) and its components in a sample of Kazakh population. The disturbance of glucose homeostasis in most cases precedes other signs of MS. We hypothesized that genetic risk assessment of beta-cell dysfunction and insulin resistance can indicate its presence before the development of leading signs of MS. Methods: Anthropometric and biochemical parameters were estimated for 1000 individuals of Kazakh population who had MS signs in accordance with the criteria of the IDF (2005), and compared with similar parameters of 1000 individuals of Kazakh population without MS. A purposeful search has been carried out for some variants of genes that demonstrated their connection with beta-cell dysfunction and insulin resistance in other populations: HNF1A gene and FTO gene. Identification of polymorphisms was carried out using the platform of the open array QuantStudio 12K Flex Real-Time PCR. The influence of polymorphisms on the occurrence of MS was assessed using logistic regression analyzes. Results: After adjusting for BMI, sex, age, we found an increased risk of MS in the case of rs1169288, rs2464196 and rs735396 of the HNF1A gene (OR 2.08, 95% CI 1.38-3.14, p = 0.032; OR 2.19, 96% CI 1,66-4,20, p = 0,031; OR 1.51, 95% CI 1.03-2.14, p = 0.019 respectively). Also, rs2751812, rs8050136, rs9939609 (OR 1.58, 98% CI 1.22-3.39, p = 0.028; OR 1.52, 97% CI 1.35-3.31, p = 0.022; OR 1.51, 99% CI 0.81-2.34, p = 0.015, respectively) of the FTO gene demonstrate the objective risk of MS, which underlines the special role of obesity in this regard. Conclusions: The study establishes the relationship of rs1169288, 2464196 and 735396 of the HNF1A and rs2751812, rs8050136, rs9939609 of the FTO with the MS in Kazakh population.
Massimiliano Chetta
Laboratory of Human genetics, ospedale Antonio Cardarelli, Italy and Department of Medicine, Surgery and Dentistry, University of Salerno, Italy
Title: Spatial and temporal distribution of small no coding RNAs (miRNAs and piRNAs) into the cell
Biography:
Massimiliano Chetta is a biologist with a specialization in medical genetics and PhD. in molecular medicine of the adult and child. He has an extensive international experience in genetics and public healt. Currently he is a biologist manager at the Cardarelli Hospital in Naples, hospital of national importance where he carries out activities of molecular biology for the oncology departmentand and post-natal cytogenetic diagnosis. In recent years he has been dedicated to the analysis of big data (whole exome, target sequencing, small RNA-Seq)
Abstract:
The diffusion of new technologies of high throughput sequencing has resulted in a large amount of sequencing data set that gave us the opportunity to shine the spotlight on different aspects of the intricate cellular networks. The 90% of the genome is transcribed following distinct regulatory pathways, tissue-specific rhythms in specific time-points. The complex regulatory networks control is realized through different types of trans-regulators TFs (transcription factors), different classes of small noncoding RNAs and steps in their maturation. All these evidences have changed the view of cellular networks regulation. However, the advances in methods that analyze RNA populations allowed a quantitative, and rapid characterization of small RNAs in cells and/or tissues producing a picture under a precise condition. All these data are quickly stored in specialized databases that become a source of information, and by a simply changing of the initial question, it can provide surprising results. We performed an analysis of complete subset sequences of small non-coding RNA (miRNA and piRNA) stored in the main data base to identify occurrence of conserved motifs and possible interplay between transcription factors and small non-coding RNAs in genome-scale regulatory networks. In particular, we analyzed the entire subgroup of Homo sapiens mature miRNA (1881 mature miRNAs sequences from http://www.mirbase.org/ftp.shtml) and piRNA (32826 piRNAs sequences from http://regulatoryrna.org/database/piRNA/download.html).
- Human Genetics | Cancer Genetics | Genetic Disorders | Molecular and Cellular Genetics | Medical Genetics | Population and Evolutionary Genetics | Cytogenetics | Epigenetics | Immunogenetics | Pharmacogenomics | Microbial Genomics | Cancer Genomics | Functional Genomics | Nutrigenomics
Location: Independence Ballroom A
Chair
David I Smith
Mayo Clinic,YSA
Co-Chair
M Eileen Dolan
University of Chicago,USA
Session Introduction
Gargi Pal
Hunter College of The City University of New York, USA
Title: Clinical absolute quantification assay for non-invasive detection of Plasmacytoma variant translocation 1-derived transcripts
Time : 14:15-14:40
Biography:
Gargi Pal has her expertise in molecular biology, cell biology and passion for improving the health, and wellbeing. She takes pride in communicating and advocating for science. Now she is working on Prostate cancer, which is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). She and Dr. Ogunwobi have developed a clinical grade assay, which can be used for the accurate quantitative detection of prostate cancer and several other diseases associated with dysregulation of Plasmocytoma variant translocation 1 (PVT1) transcripts.
Abstract:
Cancer is the second most common cause of deaths in the United States. One of the most important susceptibility loci for cancer is the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is dysregulated in many cancers, as well as immune diseases like vitiligo and asthma. PVT1 has at least 12 exons that make separate transcripts which may have different functions. In this study we have developed a patentpending real-time quantitative polymerase chain reaction-based assay for absolute quantitation of PVT1 exons 9, 4A, 4B to enable accurate, reproducible, and quantifiable detection. Standards were developed for the creation of a linear standard curve representing a broad range of concentrations. The efficacy of this assay was evaluated by quantitatively measuring detection of these transcripts in different cancer cell lines, human tissues, human serum, and mouse plasma samples. The results indicate that the assay can be used to quantify both low and high copy numbers. This is the first report of developing a clinical assay for reproducible and non-invasive detection of PVT1-derived transcripts. This clinical-grade assay is found to be accurate, reproducible, and useful in detecting the level of PVT1-derived transcripts in different samples. This novel assay is a sensitive and suitable assay which can be used for routine non-invasive clinical testing.
Laura Scheinfeldt
Coriell Institute for Medical Research, USA
Title: Reducing ascertainment bias in Pharmacogenomic research
Time : 14:40-15:05
Biography:
Laura Scheinfeldt is program manager and principal investigator of the National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center at the Coriell Institute for Medical Research. Her research has focused on the distribution of human genetic variation within and among populations living across the world and the relationship between genetic and phenotypic variation. Using an interdisciplinary approach, she has studied how genetic variation contributes to disease and drug response and has applied this research to precision medicine. For the past five years, she has worked with the Coriell Personalized Medicine Collaborative (CPMC) to understand how genetic and non-genetic factors impact health-related traits; she has worked on understanding how ascertainment biases in the current research literature impact marginalized populations and contribute to health disparities; and she has worked on identifying the subset of common genetic risk factors for complex disease that may motivate preventive health behaviors.
Abstract:
Statement of the Problem: There is a well-established contribution of genetic variation to drug response that has resulted in the expectation of personalized optimization of drug efficacy and the minimization of drug toxicity. While the majority of drugs currently used in clinical practice lack companion genetic tests for therapeutic effects and/or adverse drug response avoidance, a variety of known genetic determinants of drug response (pharmacogenetics) have been documented and clinically validated. One of the challenges facing the comprehensive identification of pharmacogenetic (PGx) variants is the documented ascertainment bias in genomic research participation. Given that the uptake of PGx data in clinical care has been relatively slow, there is an opportunity to reduce this bias and increase the generalizability of results to clinical communities across the United States. The purpose of this study is to explore the impact of ascertainment bias on the translation of PGx research into clinical care. Findings: PGx panels such as the Affymetrix DMET array are missing important PGx variants that are rare in populations of European descent. Conclusion & Significance: There is an opportunity to expand the communities that participate in genomic and pharmacogenomic research, reduce sampling ascertainment bias, and increase the generalizability of genomic research findings to peoples living in the United States.
Byung Yoon Choi
Seoul National University Bundang Hospital, South Korea
Title: A customized auditory rehabilitation based on the genetic etiology: A new auditory neuropathy spectrum disorder gene
Time : 15:05-15:30
Biography:
Byung-Yoon Choi is both a geneticist and otologic surgeon. He has her expertise in genetic deafness and customized auditory rehabilitation based on genetic etiology. He pursues a discovery a new deafness gene and elucidation of a function of the genes. He is specially interested in application of the information obtained from the bench into clinics.
Abstract:
Cochlear glia-like supporting cells (GLSs) have been suggested to play an important role in the development and maintenance of an auditory system. However, genes that are primarily expressed in GLSs have never been clearly associated with progressive human deafness. Herein, we present a novel deafness locus and a new human auditory neuropathy spectrum disorder (ANSD) gene, AUDITORIN mainly expressed in GLSs. We specify p.R372X of AUDITORIN as a cause of the significant deterioration of speech perception in humans. AUDITORIN was shown to encode a novel, cationic channel, contributing to the enigmatic passive conductance current in GLSs. This current is abolished by gene-silencing or in p.R372X knock-in mouse in a dominant-negative fashion. Because the pathogenic effect of this variant was limited to GLSs, a cochlear implant that electrically stimulates spiral ganglion neurons was performed on the affected ANSD subjects and their speech perception ability was successfully restored. Our study elucidates an unprecedented pathological role of a cochlear GLSs by identifying a novel deafness gene and its causal relationship with ANSD, introducing a new disease entity called auditory gliopathy and paving the way for precision medicine in deafness.
Meryem Alagoz
Biruni University, Turkey
Title: Deficiency in ORC1 affects heterochromatin organization, sister chromatid cohesion and the response to DNA damage in Meier-Gorlin syndrome
Time : 15:30-15:55
Biography:
Meryem Alagöz completed her BSc studies in Medical Biology at CerrahpaÅŸa Medical School and pursued her MSc studies in Molecular Biology and Genetic Engineering at the University of Sussex. She attained her PhD from the University of Sussex. Her PhD Project involved in the investigation of genetic alterations in human breast and ovarian cancer. She had worked as a Post-doctoral research fellow at Kings College and Imperial College. She worked at the University of Sussex for 7 years as a research fellow and still collaborating with them for her research. She has been investigating the molecular mechanisms involved in the development of human diseases such as cancer and brain disorders. She has been working as an assistant professor at the Molecular Biology and Genetics Department of Biruni University since February 2017. She has been setting up the research and diagnostic laboratories at the Genome Centre employing advances technologies such as Next generation sequencing. In near future, she would like to focus on DNA damage and repair field where she gained extensive experience during her studies and research. She will employ these experiences to research into the broader area of genetic disorders.
Abstract:
DNA replication origins are licensed by the pre-replication complex, which encompasses six components of the origin recognition complex (ORC), CDT1, CDC6, and the MCM helicase. Mutations in pre-replication complex components have been shown to cause Meier-Gorlin Syndrome (MGS) a disorder characterized by microcephaly, short stature, and patellar abnormalities. ORC components have also been shown to localize to heterochromatin and impact on the heterochromatin superstructure. Here, we show that deficiency in ORC1 in MGS patient cells impairs sister chromatid cohesion and formation of heterochromatin via a process we refer to as 'decompaction'. Comparison to other human cell lines with disordered chromatin, ICF (Immunodeficiency- Centromere instability-Facial anomalies syndrome) and RETT syndrome, revealed that the effect of Orc1 deficiency on heterochromatin structure is profound in human cell lines. Depletion of ORC1 by siRNA knockdown affects heterochromatin assembly and diminishes levels of HP1 and H3K9Me3. Similar changes were observed in MGS patient cells with mutations in ORC1. We investigated the cohesion of sister chromatids using a fluorescent in-situ hybridization assay and observed an impairment in the cohesion of sister chromatids. We examined aspects of the DNA damage response which are known to be sensitive to heterochromatin status to provide evidence for a functional impact of the disordered heterochromatin. ORC1 deficiency impairs DSB repair carried out by homologous recombination. We suggest that these results can be explained by our 'decompaction' model. Where ORC1 deficiency leads to improperly structured heterochromatin. These results suggest that ORC has a role in regulating heterochromatin structure and DSB repair by homologous recombination which is distinct to the role in origin licensing.
Jean Philippe Stephan
Center for excellence Pharmacological Screening, France
Title: Pharmacogenomics boosted high content screening approaches for drug discovery
Time : 16:15-16:40
Biography:
Jean-Philippe Stéphan, originally from Rennes, Brittany, France, received his Ph.D. in Developmental Biology from Pierre and Marie Curie University (Paris VI, France). After a postdoctoral fellowship at Genentech, he was hired as a Research Scientist in the Assay and Automation Technology department (AAT) at Genentech, Inc. Over his 17 years tenure at Genentech, Dr. Stéphan contributed to multiple research programs including the characterization of multiple therapeutic antibodies and later the target discovery when he was directing the functional genomics group. Dr Stéphan had a long-term interest in the development, evaluation, and implementation of new technologies that could be applied to the discovery and characterization of new therapeutics. In 2014, Dr Stéphan joined l’Institut de Recherche SERVIER as head of the cellular Models and HTS department. Since February 2017, Dr Stéphan is now directing SERVIER center of excellence for Pharmacological Screening, Compound Management, and Biobanking.
Abstract:
Despite the fact that many drugs on the market today were discovered through phenotypic screens, this approach is considered by many investigators as a “black box” and in many cases, target centric biochemical or cellular assays are preferred to support the initial drug discovery steps. Nevertheless, this “white box” approach clearly does not deliver all the expected success in term of drug developments, mostly due to the lack of pathophysiological relevance of the models. Now, the pharmaceutical industry is implementing new discovery paradigms to try to solve the current disconnect between the drug discovery process and the human clinical trials. Among the myriad of new technologies and approaches currently considered, High Content Screening combined with biosensors technologies, genome-editing and stem cell-derived cellular models offer the opportunity to drastically transform phenotypic screening, linking target engagement and phenotypic impacts in more relevant in vitro models. This new generation of phenotypic screens combined with the current drug discovery strategies represent a true opportunity to fulfill the gap between the screening dish and the patients. Despite the tremendous potential of HCS, researchers have to carefully consider various aspects of the projects before deploying the technology and this presentation will go through several examples highlighting the current strengths and weaknesses of the approach.
Xinzhong Li
Plymouth University, UK
Title: Cross-talk between Brain cancer and Alzheimer’s disease
Time : 16:40-17:05
Biography:
Dr Xinzhong Li was born in China and completed his educations from Xi'an Jiaotong University, China. Currently, he is a lecturer in biostatistics and bioinformatics at Plymouth University Peninsula Schools of Medicine and Dentistry, UK. He has wide research interests and mainly focuses on biomarker discovery and early diagnosis of diseases, including dementia and cancer. He is the coordinator of EU H2020 Marie Skłodowska-Curie Action AiPBAND project aiming to train 14 PhD students in the field of early diagnosis of brain cancer.
Xinzhong
Abstract:
Statement of the Problem: Different to other cancers, brain tumors deaths are rising, representing 2.6% of all deaths from cancer and kill more children and people under 40 than any other cancers. As an important brain disease, Alzheimer’s disease (AD) cause huge healthcare, social and economic problems as well, no cure exists for the AD as well as for brain cancer. Previous studies have evaluated gene expression in these two brain diseases to identify mechanistic processes, some studies revealed that transcriptional signaling pathways inversely regulated in AD and glioblastoma multiform (GBM), meanwhile some studies suggested patients with AD have a higher risk of developing GBM. The inconsistent conclusion may be caused by the limited size of the samples studied. Methodology & Theoretical Orientation: Systematically studying the entire transcriptome on a big scale may profound potentially novel interactions, common pathways between AD and GBM, and lead to further understanding of their pathophysiology. A novel meta-analysis approach is implemented to identify differentially expressed genes (DEGs) in published datasets comprising GBM and controls, AD and controls. Ingenuity Pathway Analysis is conducted afterward to identify the most perturbed pathways. Protein-protein interaction network analysis is completed to discover the key interactions. Findings: Significant DEGs are identified in GBM including some novel DEGs, as well as common pathways shared between GBM and AD. Conclusion & Significance: GBM and AD do share common pathways and DEGs which indicate both diseases may be caused by the same reasons. Further investigates are necessary to confirm the findings which may lead to new treatments for both diseases.
Binata Marik
AIIMS, New Delhi, India
Title: Mutational screening in patients with familial hypophosphatemic rickets
Biography:
Binata Marik is currently doing PhD in Human Genetics at All India Institute of Medical Sciences (AIIMS), New Delhi, India. She has done Masters in Biotechnology from AIIMS, New Delhi, India. She has an expertise in Pediatric Genetics and Cytogenetics. She is working on “Genetics of refractory rickets”. She knows the laboratory techniques used for human and molecular genetics research such as DNA isolation, Polymerase Chain Reaction (PCR), Agarose gel electrophoresis, Polyacrylamide Gel electrophoresis (PAGE), Sanger sequencing and Karyotyping. She has knowledge in bioinformatics and knows how to analyze the massive data of exome sequencing and to predict the pathogenicity of the genetic variations.
Abstract:
Introduction: Hypophosphatemic rickets, characterized by hypophosphatemia and defective bone mineralization, is predominantly inherited as an X-linked dominant condition caused by inactivating PHEX mutations. Autosomal dominant and recessive forms due to mutations in FGF23, DMP1, ENPPI, and SLC34A3 respectively are also documented. Aim: To identify mutations in cases with familial hypophosphatemic rickets (FHR) and their family members. Patients and Methods: The three FHR patients (probands) were born out of non-consanguineous marriages. In the family I, the patient and her mother were affected, in family II, the patient, her brother, and mother were affected while family III had two sisters, their father and paternal uncle affected. Clinical and family history was documented and 5ml blood drawn for DNA extraction. PHEX exons were screened by direct sequencing and result analyzed using in silico tools. Whole Exome Sequencing (WES) was done to find involvement of genes responsible for intra-familial variability seen in the affected members, and validation of mutations was done by Sanger sequencing. Results: The patients had short stature, limb deformities, and low serum phosphate. PHEX screening revealed three mutations in three patients and their affected family members, of which one was novel missense (c.2048T>A) and two reported nonsense and missense (c.871C>T; c.1601C>T) mutations respectively. Two families presented with intra-familial variability in disease phenotype. The paternal uncle of family III had dental anomalies and mother of the family I had short stature. WES was done for the family I, and family III probands, father and paternal uncle. Results revealed a novel PHEX mutation G>C in exon 21 in the family I proband, which was absent in her mother but did not reveal any additional mutations, other than c.1601C>T in family III. Conclusion: This study reports two novel PHEX mutations and also suggests that PHEX may be mainly responsible for FHR in India.
Session Introduction
Binata Marik
AIIMS, New Delhi, India
Title: Mutational screening in patients with familial hypophosphatemic rickets
Time : 17:05-17:30
Biography:
Binata Marik is currently doing PhD in Human Genetics at All India Institute of Medical Sciences (AIIMS), New Delhi, India. She has done Masters in Biotechnology from AIIMS, New Delhi, India. She has an expertise in Pediatric Genetics and Cytogenetics. She is working on “Genetics of refractory rickets”. She knows the laboratory techniques used for human and molecular genetics research such as DNA isolation, Polymerase Chain Reaction (PCR), Agarose gel electrophoresis, Polyacrylamide Gel electrophoresis (PAGE), Sanger sequencing and Karyotyping. She has knowledge in bioinformatics and knows how to analyze the massive data of exome sequencing and to predict the pathogenicity of the genetic variations.
Abstract:
Introduction: Hypophosphatemic rickets, characterized by hypophosphatemia and defective bone mineralization, is predominantly inherited as an X-linked dominant condition caused by inactivating PHEX mutations. Autosomal dominant and recessive forms due to mutations in FGF23, DMP1, ENPPI, and SLC34A3 respectively are also documented. Aim: To identify mutations in cases with familial hypophosphatemic rickets (FHR) and their family members. Patients and Methods: The three FHR patients (probands) were born out of non-consanguineous marriages. In the family I, the patient and her mother were affected, in family II, the patient, her brother, and mother were affected while family III had two sisters, their father and paternal uncle affected. Clinical and family history was documented and 5ml blood drawn for DNA extraction. PHEX exons were screened by direct sequencing and result analyzed using in silico tools. Whole Exome Sequencing (WES) was done to find involvement of genes responsible for intra-familial variability seen in the affected members, and validation of mutations was done by Sanger sequencing. Results: The patients had short stature, limb deformities, and low serum phosphate. PHEX screening revealed three mutations in three patients and their affected family members, of which one was novel missense (c.2048T>A) and two reported nonsense and missense (c.871C>T; c.1601C>T) mutations respectively. Two families presented with intra-familial variability in disease phenotype. The paternal uncle of family III had dental anomalies and mother of the family I had short stature. WES was done for the family I, and family III probands, father and paternal uncle. Results revealed a novel PHEX mutation G>C in exon 21 in the family I proband, which was absent in her mother but did not reveal any additional mutations, other than c.1601C>T in family III. Conclusion: This study reports two novel PHEX mutations and also suggests that PHEX may be mainly responsible for FHR in India.
Alec R Chapman
Harvard University, USA
Title: Correlated transcription modules uncovered by high-precision single-cell transcriptomics
Time : 17:30-17:55
Biography:
Alec Chapman is a postdoctoral researcher in the lab of Sunney Xie at Harvard University. His work has focused on developing new methods for single cell genome and transcriptome sequencing and applying these methods to study biological systems ranging from development to cancer. He is interested in regulation of gene expression and how cells make decisions in the presence of noise. He received his Ph.D. from Harvard University and did his undergraduate work at Princeton University.
Abstract:
Single cell transcriptome sequencing has provided a wealth of data about differential expression across cell types and conditions. However, such data are of limited utility for inferring regulatory relationships between genes because multiple regulatory pathways and their downstream targets are up- or down-regulated in unison. Here, we generate more specific and functionally enriched modules by clustering genes according to correlations in steady-state expression fluctuations. We developed a novel single-cell RNA-seq method called MALBAC-DT to measure these correlations in homogenous cell populations and found numerous intercorrelated gene clusters with cell-type specific functional enrichments. Literature analysis and RNAi knockdown of the TP53 transcription factor confirmed that a 50-gene module enriched for p53 signaling consisted almost entirely of direct TP53 targets. This approach provides a powerful way to advance our functional understanding of the genome.
Jagriti Sethi
University of Plymouth, UK
Title: Graphene biosensors for label-free detection of blood-based biomarkers for Alzheimer’s disease
Biography:
Ms. Jagriti Sethi is from New Delhi, India and is an Early stage researcher in Plymouth University under the BBDiag Network. She received her bachelor’s and Master's in Nanotechnology (2016) from Amity Institute of Nanotechnology, Amity University, India. She has worked with institutions like Central Scientific Instruments Organization and University of Paris and has carried out research on Biocompatible Nanocomposites and 2D Nano sheets as a part of her undergraduate and postgraduate research. She is currently working on the Fabrication of biosensors for blood-based AD biomarker.
Abstract:
Statement of the Problem: Alzheimer’s disease is the most common form of dementia leading to a massive irreversible neuronal loss and cognitive decline. It affects over 7 million people in Europe and 5.5 million in America and this figure is expected to double every 20 years as the population ages. Early detection of the AD is the key requirement for developing disease-modifying treatments as studies show that pathology exceeds symptom by years. The existing techniques for detection using CSF and Imaging biomarkers are highly expensive and invasive. Blood-based biomarkers, however, can provide a simple and effective way for the screening of AD patients. The talk covers the latest progress in the EU H2020 BBDiag research project, for the development of blood biomarker-based diagnostics for early-stage AD employing by multiplexed graphene biosensor arrays. Methodology & Theoretical Orientation: Two novel graphene biosensors were developed for label-free detection of DNA and protein biomarkers, a graphene immunoFET for detection of protein markers and a rGO-graphene electrode for detection of DNA markers. Findings: The rGO electrode shows enhanced redox current up to 40% higher in comparison with electrodes of bare graphene due to the combination of a high number of electroactive sites on rGO and high conductivity of pristine graphene. A linear range from 10-7M to 10-12M is demonstrated for the biosensor with a detection limit of 1.58 x 10-13M. The immunoFET showed a unique resistance change pattern with high reproducibility and an ultralow detection limit of 1pg mL-1 and high sensitivity of 0.30 Ω/ng/mL. Conclusion & Significance: We have demonstrated that graphene biosensors can be employed for ultra-sensitive and label-free detection of DNA and proteomic disease biomarkers. The work may lead to the development of cost-effective and minimally invasive point of care diagnostic devices for routine screening of Alzheimer’s disease with a panel of biomarkers.