GeneExpression Systems & Appasani Research Conferences (ARCEI.ORG)
Jointly Presents

Inaugural

European Genomics-2010 Meeting
On
‘Genotyping, SNiPs to Traits & Diseases’
September 20 – 21, 2010

Oriel College
University of Oxford, Oxford, United Kingdom

“A Unique Theme to Combine Genomics with Disease Biology”

Meeting Venue: Oriel College-Oxford University:   
When the quarrel between Henry II and Philip Augustus in 1167 made it impossible for English students to attend the University of Paris, the opportunity for developing a similar institution arose at Oxford. Dominican friars established their main house of study there on arrival in England in 1221 and were followed in 1224 by the Franciscans. Divinity was constituted as a superior faculty and students were admitted who already possessed an arts degree.

Oriel College founded in 1326 by King Edward II, this is the fifth oldest college at Oxford University and intended to help students who were already graduates to obtain a further degree. Past 684 years Oriel continued to maintain its intellectual standards, and admitted women for the first time in 1985. Oriel’s notable alumni include Sir Walter Raleigh, Thomas Harriot, Cecil Rhodes, Cardinal Newman, and two Nobel Laureates: Sir Alexander Todd (Chemistry), and James Meade (Economics).

Oriel always a place for higher learning, and authorities in various fields meet hear and share knowledge. Attend this meeting and be part of the rich heritage of education…….

Topics or Highlights of the Meeting:
Genomic Studies in plants and animal model organisms
Genotyping with various Technological Platforms
Discovery of Single Nucleotide Polymorphisms & Human Trait Genes
SNP Hybrid Arrays & Mapping Studies
Copy Number & Structural Variations
Genome Variation & Allele-specific Gene Expression
Haplotype Mapping & Variome Projects
Comparative Genomic hybridization
Global Variation in the human Genome & Disease causing variants
SNP Genotyping and real-rime PCR
Disease-associated SNPs
Disease Genetics and Diagnostics
Exponential Quantitative Trait Loss

AGENDA/SPEAKERS (click here for a detailed agenda)

Monday, September 20, 2010
7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 A.M: Continental breakfast
8:00 - 9:00 A.M: Technology Session I
10.00 AM – 6.00 PM Scientific Sessions

Tuesday, September 21, 2010
7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 A.M: Continental breakfast
8:00 - 9:00 A.M: Technology Session I
10.00 AM – 6.00 PM Scientific Sessions

Scientific Committee:

	Krishnarao Appasani, Ph.D., MBA Founder & CEO GeneExpression Systems, Inc, Waltham, MA, USA
	Ioannis Ragoussis,PhD. Head of Genomics Wellcome Trust Centre for Human Genetics University of Oxford, Oxford, UK

Confirmed Speakers:

	Meredith Yeager, PhD.                                Scientific Director of Core Genotyping Facility SAIC-National Cancer Institute, NIH, Gaithersburg, MD, USA Title: Genome-wide association studies in cancer
	Antonio M. Persico, M.D.                 Associate Professor. in Physiology PRABB-Lab. of Molecular Psychiatry & Neurogenetics University Campus Bio-Medico, Rome, Italy Title: Autism: Where genetics meets the immune systems
	Lukasz Filip Grochola, MD.                         Ludwig Institute for Cancer Research University of Oxford, Oxford, United Kingdom Title: The identification and characterization of SNPs that affect human cancer
	Kumarasamy Thangaraj, Ph.D. Scientist & Group Leader Centre for Cellular and Molecular Biology Hyderabad, India Title: Reconstructing Indian population history based on genomics
	Dr. Michael N. Weedon                                Lecturer in Diabetes Research & Vascular Medicine Peninsula Medical School Exeter, UK Title: Common variants inHMGA2 associated population
	Naoyuki Kamatani, MD., PhD.                     Director of the Center for Genomic Medicine RIKEN Yokohama Institute Yokohama-shi, Kanagawa, Japan Title: Genome-Wide Association studies in Japanese population
	Dr. D. Timothy Bishop                      Leeds Institute of Molecular Medicine St. James Univ. Hospital, Leeds, UK Title: Genome-wide association studies in melanoma
	Dr. Rui Medeiros                              Professor of Pharmacogenomics Porto University & Portugese Inst. of Oncology Porto, Portugal Title: Polymorphisms in prostate cancer
	Caleb Webber, PhD.                                                 Postdoctoral Fellow in the Lab of Dr. Chris Ponting MRC Functional Genomics Unit University of Oxford, Oxford, UK Title: Identifying genes and processes that underlie autism and intellectual disability
	Hitoshi Kurumizaka, PhD.                           Professor of Science and Engineering Waseda University Tokyo, Japan Title: Structural and biochemical studies of DMC1 polymorphisms in the human population
	Swee Lay Thein, DSc., FRCP                                                Professor of Molecular Haematology King’s College London School of Medicine London, UK Title: Genetic studies in sickle cell disease
	Dr. Martin Farrall                                          University Lecturer in Cardiovascular Medicine Keble College, Oxford, UK Title: Quantitative traits in cardiac diseases
	Patricia Munroe, Ph.D. Professor of Molecular Medicine Queen Mary University of London, UK Tile: Genome-wide Association studies associated with blood pressure
	Amanada McCann, PhD.                  Senior Lecturer in the School of Medicine & Medical Science Conway Institute, University College of Dublin, Ireland Title: Hypoxia mirrored in the epigenome and implications for Chemo-resistance
	Dr. Jan H. Veldink                                         Staff Member in the Neurology University Medical Center Utrecht, The Netherlands Title: Copy-number variation in sporadic amyotrophic lateral sclerosis: A genome-wide screen
	Panos Deloukas, PhD.                                 Senior Investigator Wellcome trust Sanger Institute, Hinxton, UK Title: TBA
	Mark Rose, PhD.                                 R&D Illumina, Inc. R&D, Cambridge, UK Title: TBA
	Lekshmy Srinivas                                                     PhD Student & Senior Research Fellow Rajiv Gandhi Centre for Biotechnology, Kerala, India Title: Global variations in cytokine gene polymorphisms with respect to South Indian Population
	Zoltan Kutalik, PhD.                          Post doctoral Fellow in Medical Genetics University of Lausanne & Swiss Institute of Bioinformatics Lausanne, Switzerland Title: Genome-wide association scan reveals major susceptibility locus in IL28B for both chronic Hepatitis C and for treatment failure
	Fiona Brew, PhD.                  Associate Director of Market Development Affymetrix UK Ltd. High Wycombe, United Kingdom Title: TBA
	Paul Haggarty, PhD. Professor & Head of Lifelong Health Division Rowett Inst. Nutrition & Health University of Aberdeen Aberdeen, Scotland Title: Polymorphism in the DNA methylation genes involved in epigenetic variation and disease

Exhibitors are welcome to reserve their booth space early!

Please contact if you are interested in speaking in the scientific or Technology workshops of this meeting.

GeneExpression Systems, Inc.
P.O. Box 540170
Waltham, MA 02454 USA
Tel: (781) 891-8181
Fax: (781) 891-8234
E-mail: Genexpsys@expressgenes.com
www.expressgenes.com

Poster Abstract Submission by Sept 15, 2010

All Abstracts

Genes, sunlight and melanoma skin cancer
Dr. D. Timothy Bishop, Professor, Leeds Cancer Research UK Centre, Section of Epidemiology & Biostatistics, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom

Risk of melanoma skin cancer is influenced by both sun exposure and genetic factors. Primary among the risk factors are skin reaction to the sun and the number of moles on a person’s skin. Recent genome-wide association studies have clarified the particular genetic determinants of phenotypes which are of most relevance in determining a person’s risk of developing this cancer. One of the main challenges understands the joint effects of genes and sun exposure as this provides the most likely route to identify those most at risk. Melanoma is usually treated successfully when found at early stages but has higher mortality among those with later stage disease at diagnosis.

Genome-wide association scan reveals major susceptibility locus in IL28B for both chronic Hepatitis C and for treatment failure
Zoltan Kutalik, PhD., Post doctoral Fellow in the Lab. of Dr. Sven Bergmann, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

The hepatitis C virus (HCV) induces chronic infection in 80% of infected individuals, half of whom do not respond to therapy. We conducted a genome-wide association study in 1362 hepatitis C infected individuals to screen for host genetic determinants of HCV persistence and response to therapy. Chronic hepatitis C was found to be associated with SNPs in the IL28B locus (rs8099917: OR=2.31, P=6.07*10-9), which encodes the antiviral cytokine interferon-lambda. Interestingly, rs8099917 was also associated with failure to respond to therapy (OR=5.19, P= 3.11*10-8), with the strongest effects in patients with HCV genotypes 1/4, where 11% of phenotypic variance is explained.

The identification and characterization of SNPs that affect human cancer
Lukasz Filip Grochola, MD., Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom

Two functional single nucleotide polymorphisms (SNPs) in the p53 network affect cancer both in humans and mouse models, thereby demonstrating that the inherited genetics of the p53 network could be utilized to further define patients in their abilities to react to stress, suppress tumour formation and respond to therapies. In order to identify additional SNPs that affect cancer, we take advantage of three well-characterized traits of both SNPs to mine genomic data-sets, namely, allelic differences in signatures of recent natural selection, cellular chemosensitivities and gender- and age-dependent sarcoma incidence. We identify SNPs in p53 network genes that associate with altered tumour formation, progression and response to chemotherapeutic treatment.

Autism: Where genetics meets the immune systems
Antonio M. Persico, M.D., Assoc. Prof. in Physiology, PRABB-Lab. of Molecular Psychiatry & Neurogenetics, University Campus Bio-Medico, Rome, Italy

Neuroanatomical, genome-wide expression, and brain imaging studies provide converging evidence of an abnormal activation of the immune system in autism, and particularly of its innate components. Yet, autism remains the psychiatric disorder displaying the highest heritability estimates. We shall present genetic and functional data on common gene variants conferring autism vulnerability, such as PRKCB1, SLC25A12, ATP2B2, ITGB3, and PON1: their direct or indirect connection with dysimmunity will be discussed. Preliminary evidence of heritable viral triggers potentially involved in autism will be presented. A unifying pathophysiological scheme will be proposed, which may apply to a sizable subgroup of autistic individuals.

Global Variations in Cytokine gene polymorphisms with respect to South Indian Population
Lekshmy Srinivas, PhD Student & Senior Research Fellow, Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

Lekshmy Srinivas and Moinak Banerjee
Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India

Cytokines, generally known as chemical messengers between immune cells, play a crucial role in mediating inflammatory and immune responses. They have been differentially associated with the risk of autoimmune and infectious diseases or graft rejection. Because cytokines play a central role in the pathophysiology of various medical illnesses, genetic polymorphism of specific cytokines and their association with specific diseases have been widely investigated. Ethnic differences exist in patterns of cytokine gene polymorphisms which correlate with population-based variations in the ability to mount an immune response. Different cytokine genotypes exist in a population, mainly as a result of geographically localised natural selection imposed by invading microbes and host–pathogen interactions. We evaluated the allelic and genotype frequencies of 10 single nucleotide polymorphisms (SNPs) in 4 different cytokine genes in a healthy population from Kerala, South India and compared it with North Indian population and other world populations using the allele frequency data obtained from the Hapmap Genome Browser Phase 3 dataset (http://hapmap.ncbi.nlm.nih.gov) and the worldwide population allele frequency database allelefrequencies.net. The allele, genotype and haplotype frequencies and Hardy–Weinberg proportions (HWP) for each SNP were determined using the population genetics analysis package software, PYPOP. Only those SNPs for which frequency data was available for all populations were used for comparison. Genotyping was carried out by PCR-RFLP and Taqman allelic discrimination assays. Linkage Disequilibrium (LD) plots were generated using Haploview and were compared between our population and Hapmap populations wherever data was available. The allele frequency distribution of the cytokine genes in different populations was used to construct a phylogenetic tree based on genetic distances. An UPGMA (Unweighted Pair Group Method with Arithmetic mean) tree was constructed based on Fst genetic distances using the software POPTREE2. We observed that the South Indian and North Indian populations clustered together with the South American and African populations while the European and Arab populations formed a separate cluster further away. The allele frequency distribution and genetic distances between South Indian population and other global populations might help us understand the epidemiology of emergence or frequent reemergence of certain diseases from a genetic viewpoint.

Fetal haemoglobin – a quantitative trait and its impact on sickle cell disease
Swee Lay Thein, DSc., FRCP, Professor of Molecular Hematology, Head of Division of Gene and Cell Based Therapy, King’s College London School of Medicine, & King’s College Hospital NHS Foundation Trust, London UK

Inter-individual variation in fetal haemoglobin (HbF, α2γ2) expression contributes substantially to disease severity in the two major β haemoglobin disorders – β thalassaemia and sickle cell disease (SCD) and much effort has been spent on understanding its regulation in adults. The beneficial effect of HbF on both disorders has been known for decades and exploited in the development of HbF reactivating agents including hydroxyurea, the only agent approved by FDA (USA) and EMEA (Europe) for the treatment of SCD. Our understanding of haemoglobin control, including the persistence of HbF synthesis in adults, is historically based on Mendelian models of inheritance of natural mutants. Indeed, a series of mutations at the β globin cluster that impairs the switch from fetal to adult haemoglobin have been characterised in a syndrome termed hereditary persistence of fetal haemoglobin (HPFH). However, HbF persists in all adults as a quantitative genetic trait that is largely controlled in a non-Mendelian fashion. From a genetics perspective, the story of HbF quantitative genetics uncannily mirrors the changing focus of human gene mapping, from candidate genes through positional cloning to genome-wide association studies (GWAS). Positional cloning has led to the identification of the QTL on 6q (HBS1L-MYB intergenic polymorphism, HMIP) in an Asian Indian family, and more recently a rare variant in KLF1 on chromosome 19p in a Maltese family with HPFH. Recent GWASs not only ‘rediscovered’ the known QTLs – Xmn1‑HBG2, and HMIP on chromosome 6q23 – but identified BCL11A on chromosome 2p16, previously known as an oncogene. The three principal QTLs account for a relatively large proportion (20%‑50%) of the phenotypic variation in HbF levels, not only in healthy adults but also in patients with these β haemoglobinopathies in diverse ethnic groups with a significant impact on clinical severity. Two of the principle QTLs (BCL11a and HMIP) include oncogenes emphasising the importance of cell proliferation and differentiation as an important contribution to the HbF phenotype and the haemoglobin ‘switch’. Functional studies suggest that BCL11A acts as a repressor of HBG1 and HBG2 expression in adults, acting with SOX6 protein. HMIP lies in a gene desert, and studies suggest that this region contains distal regulatory sequences that affect HbF control via alteration of kinetics of erythroid maturation and differentiation, a role further supported by its pleiotropic effects on other haematological parameters – erythrocyte volume and erythrocytosis, platelet and monocyte counts. KLF1 has been shown to function as a key activator of BCL11A. Haploinsufficiency for KLF1 reduces BCL11A expression and increases HbF (α2γ2) expression.
Challenges that remain include delineating the causal variants and identifying other QTLs to improve the prediction of one’s ability to produce HbF and the molecular network of different HbF-modifying loci. To this end, we need to fine map these loci perform independent GWASs in populations from the African continent.

Genome-wide association studies in cancer
Meredith Yeager, PhD., Scientific Director of Core Genotyping Facility, SAIC-National Cancer Institute, NIH, Gaithersburg, MD, USA

Recent advances in human genomics have provided the opportunity to rapidly scan the genomes of large numbers of individuals in genome-wide association studies (GWAS).  A number of GWAS and follow-up studies in cancer and related phenotypes are ongoing at the Core Genotyping Facility (CGF) of the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute (NCI).  Studies of prostate, breast, pancreatic, lung, renal, bladder, brain, gastric and testicular cancers have been conducted in more than 60,000 individuals and have yielded association findings that warrant further investigation to determine the underlying genetic variants contributing to disease.  Discussed here is our GWAS approach, progress to date, initial findings, and future directions.

Structural and biochemical studies of DMC1 polymorphisms in the human population
Hitoshi Kurumizaka, PhD., Professor of Science and Engineering,
Graduate School of Advanced Science & Engineering, Waseda University, Tokyo, Japan

The DMC1 protein is an essential, meiosis-specific DNA recombinase that catalyzes two successive recombination reactions, homologous pairing and strand exchange, between homologous chromosomes. We found that a human DMC1 polymorphic variant, DMC1-M200V, is moderately defective in catalyzing in vitro recombination reactions. The crystal structure of DMC1-M200V revealed that the hydrophobic interaction that bridges the two a helices in the core ATPase domain was reduced in the variant. We also found that the biochemical properties of the DMC1-I37N variant, another human DMC1 polymorphic variant, were quite different from those of conventional DMC1. Functional interactions of these DMC1 variants with the DMC1 activators will be discussed.

Genomic variations: history, health and disease of India populations
Kumarasamy Thangaraj, Ph.D., Scientist & Group Leader, Evolutionary and Medical Genetics Laboratory, Centre for Cellular and Molecular Biology, Hyderabad, India

India represents one of the largest sources of human diversity, comprising 4635 anthropologically well-defined populations; hence studies on Indian populations would provide insight into their complex origin, history and genetic affinities. In order to answer long-held question about the origin of diverse Indian populations, we have analyzed ~18,000 individuals belonging to several tribal, caste and religious groups with ancestry informative genetic markers. Our study revealed that the enigmatic Andaman Islanders are the first anatomically modern humans migrated out-of-Africa about 65-70 thousand years ago. Recently, we have screened 560,123 SNPs across the genomes of 132 individuals belonging to 25 diverse groups from 14 Indian states, and six language groups. Our study revealed that a relatively small group of ancestors founded most Indian groups, which then remained largely isolated with limited gene flow for long periods of time. We also identified two main ancestral groups in India: an "Ancestral North Indian (ANI)", which is distantly related to those in the Middle East, Central Asia, and Europe, and an "Ancestral South Indian (ASI)", not related to groups outside India. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Our results show that genetics patterns in Indian populations have been shaped by a long history of genetic isolation between different groups that predates the caste system in place in India during colonialism. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive and complex diseases in India. My presentation would cover, both genetic variation and its implications in disease among Indian populations.

Hypoxia mirrored in the Epigenome; Implications for Chemo-Resistance
Amanada McCann, PhD., Senior Lecturer & Conway Fellow, School of Medicine & Conway Institute, University College of Dublin, Dublin, Ireland

Tumour hypoxia is a key feature of the tumour microenvironment (TME).  Moreover hypoxic tumours by their very nature are clinically aggressive and chemoresistant.  We have identified a significantly altered cellular phenotype in response to chronic hypoxia as characterised by increased receptor-mediated apoptotic resistance, the induction of cellular senescence, increased invasion and the increased secretion of IL6 and IL8 cytokines.  In association with these phenotypic changes and the absence of HIF-1α protein expression we have demonstrated significant increases in global levels of DNA methylation and H3K9 histone acetylation in these cells, concomitant with the increased expression of DNA methyltransferase DMNT3b and gene-specific changes in DNA methylation at key imprinting loci.  These epigenetic signatures may represent an additional mechanism to promote and maintain a hypoxic-adapted cellular phenotype with a potential role in tumour development. The implications of these findings in relation to Paclitaxel (Taxol)  Resistance in both breast and ovarian cancer is also discussed.

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Gene hunting in ALS: the search for high hanging fruit?
Jan Herman Veldink, MD, PhD., Staff Member, Rudolf Magnus Institute of Neuroscience,
University Medical Center Utrecht, Utrecht, The Netherlands

Although for Mendelian ALS, rare causal mutations are being identified, for non-Mendelian ALS the identification of genes has proven to be difficult, despite large international efforts. An overview will be provided of these efforts, explanations for a relative lack of identified genes, and methods and strategies to move forward.

Identifying genes and processes that underlie autism and intellectual disability
Caleb Webber, PhD., Postdoctoral Fellow in the Lab of Dr. Chris Ponting, MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom

We have exploited decades of experimental results obtained from the laboratory mouse as a functional genomics resource to better understand neurodevelopmental disease. Here, we show how the application of this data, along with other functional genomics resources, can provide insights in to the role of rare copy number variants in intellectual disability/developmental delay and autism. Within different disease-associated sets of CNVs, we identify numerous significantly enriched mouse phenotypic-associations among the overlapped human genes. These associations provide causal hypotheses for a significant proportion of these CNVs and identify relevant and currently-available mouse models for further study.

Genome-Wide Association studies in Japanese population
Naoyuki Kamatani, MD., PhD., Director of the Center for Genomic Medicine
RIKEN Yokohama Institute, Yokohama-shi, Kanagawa 230-0045, Japan

Genome-wide association study (GWAS) is a powerful method to identify associations between genomic variations and traits. This approach was first reported from RIKEN in 2002 and has expanded to a significant proportion of the researches in human genetics. We have identified genomic variations associated with many diseases including myocardial infarction, rheumatoid arthritis, osteoarthritis, hepatitis B, endometriosis and some cancers by GWAS.  We have also focused on QTL analysis targeted at physical traits like height, biochemical traits like BUN and hematological traits like platelet count. Comparison of the results from Japanese with those from Europeans has exhibited some similarities and differences.

Risk factors, genes and coronary disease
Martin Farrall, FRCPath., University Lecturer, Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics & Keble College, Oxford, UK