Host Genomics of HIV-1

Size: px
Start display at page:

Download "Host Genomics of HIV-1"

Transcription

1 4 th International Workshop on HIV & Aging Host Genomics of HIV-1 Paul McLaren École Polytechnique Fédérale de Lausanne - EPFL Lausanne, Switzerland paul.mclaren@epfl.ch

2 Complex trait genetics Phenotypic variation

3 Complex trait genetics Genetic variation (single nucleotide polymorphisms) Phenotypic variation

4 Complex trait genetics Environmental influences Genetic variation (single nucleotide polymorphisms) Phenotypic variation

5 Key developments in human genetics

6 <<<<<1% Allele frequency >5% Paradigm of complex trait genetics Clinical impact

7 <<<<<1% Allele frequency >5% Paradigm of complex trait genetics Genome-wide association studies Clinical impact

8 <<<<<1% Allele frequency >5% Sequencing studies Paradigm of complex trait genetics Genome-wide association studies Clinical impact

9 GWAS: A primer Common variants (>5% frequency) that cause (or tag variants that cause) disease can be detected by comparing variant frequencies in large samples of cases and controls General workflow: 1) Recruit patients and controls 2) Genotype at a large number of sites (>1M) 3) Compare variant frequency (controlling for confounders) 4) Find friends with similar samples and share data

10 The history and success of GWAS 2007 Data: Slide courtesy of S Ripke and S Pulit

11 The history and success of GWAS 2008 Data: Slide courtesy of S Ripke and S Pulit

12 The history and success of GWAS 2009 Data: Slide courtesy of S Ripke and S Pulit

13 The history and success of GWAS 2010 Data: Slide courtesy of S Ripke and S Pulit

14 The history and success of GWAS 2011 Data: Slide courtesy of S Ripke and S Pulit

15 The history and success of GWAS 2012 Data: Slide courtesy of S Ripke and S Pulit

16 >1,500 associations published for 240 traits Through

17 HIV host genetic studies: clinical phenotypes Disease progression Acquisition McLaren et al PLoS Path 2013 Infection

18 HIV host genetic studies: clinical phenotypes Disease progression Acquisition HIV Control McLaren et al PLoS Path 2013 Infection

19

20 Genome-wide SNP information acquired on 3,622 patients 1KG 16.8M SNPs 25.4M 1KG SNPs 15.6M 1KG SNPs After imputation test each SNP for association with HIV-1 control/progression

21 MHC is the major genetic determinant of host control

22 MHC is the major genetic determinant of host control

23 MHC is the major genetic determinant of host control Science 1996 Sep 27;273(5283):

24 Multiple independent signals in the MHC Pereyra, Jia and McLaren et al, Science 2010

25 Multiple independent signals in the MHC Pereyra, Jia and McLaren et al, Science 2010

26 Multiple HLA-B alleles impact control/progression

27 HLA alleles are defined by amino acid sequence

28 HLA alleles are defined by amino acid sequence Progression Control Testing for association per position rather than per allele can identify key residues

29 Amino acid positions are more strongly associated than classical alleles Pereyra, Jia and McLaren et al, Science 2010

30 Amino acid positions are more strongly associated than classical alleles Pereyra, Jia and McLaren et al, Science 2010

31 Multiple alleles at key positions associate with host control and determine set point IHCS SHCS Pereyra, Jia and McLaren et al, Science 2010

32 Top associated amino acid positions map to the peptide binding cleft Pereyra, Jia and McLaren et al, Science 2010

33 Amino acid associations in HLA-B African Americans B*57:03 B*81:01 McLaren et al, Hum Mol Genet 2012

34 Amino acid associations in HLA-B African Americans B*57:03 B*81:01 McLaren et al, Hum Mol Genet 2012

35 Positions in and outside of the binding groove contribute to HIV control McLaren et al, Hum Mol Genet 2012

36 Science 1996 Sep 27;273(5283):

37 Science 1996 Sep 27;273(5283): Science 2010 Dec 10;330(6010): McLaren et al, Hum. Mol. Genet [In revision]

38 Conclusions: HIV-1 control Genome wide scan of common genetic variation shows strong effects in the MHC Functional fine-mapping implicates amino acid positions within HLA-B as key to determining HIV control These explain most, but not all, of the SNP association signal Apps et al Science 2013 Next step: Meta-analysis of HIV-1 progression data from worldwide cohorts

39 G2G: Closing the loop Human genetic variation 1 GWAS Viral load

40 G2G: Closing the loop Human genetic variation 1 GWAS Viral load 2077 GWASs (1 per variable HIV amino acid) HIV-1 sequence variation

41 G2G: Closing the loop Human genetic variation 1 GWAS Viral load 2077 GWASs (1 per variable HIV amino acid) HIV-1 sequence variation 1 proteome-wide association study

42 HIV-1 genome-to-genome study 1,100 study participants Caucasians infected with subtype B HIV-1 Paired genetic data: Human: genome-wide genotypes from GWAS HIV-1: full-length consensus sequence

43 Human SNPs Viral Load HIV sequence mutations Science 2007 Aug 17;317(5840):944-7

44 Human SNPs Viral Load HIV sequence mutations Science 2007 Aug 17;317(5840):944-7 Human SNPs Viral Load HIV sequence mutations 2013 Oct 29; 2:e01123

45 SNPs, HLA and CTL epitopes

46 Conclusions Host genetics has a role to play in understanding infectious disease biology The MHC region is the major host genetic determinant of HIV outcome Majority of the genetic signal maps to the binding groove of HLA-B Integrating virus with host genetic data is a powerful new method for infectious disease association studies

47 Prospects for the future More samples GWAS data on >10,000 HIV patients obtained through collaboration ICGH More variants Rare and structural variants not covered by GWAS Deep sequencing More phenotypes Viral load is the tip of the phenotypic iceberg Where possible leverage existing data to answer new questions

48 Jacques Fellay Istvan Bartha Paul de Bakker Stephan Ripke Xiaoming Jia Amalio Telenti Bruce Walker Florencia Pereyra All collaborators in the IHCS, ICGH and G2G consortia

Supplementary Figure 1 Dosage correlation between imputed and genotyped alleles Imputed dosages (0 to 2) of 2-digit alleles (red) and 4-digit alleles

Supplementary Figure 1 Dosage correlation between imputed and genotyped alleles Imputed dosages (0 to 2) of 2-digit alleles (red) and 4-digit alleles Supplementary Figure 1 Dosage correlation between imputed and genotyped alleles Imputed dosages (0 to 2) of 2-digit alleles (red) and 4-digit alleles (green) of (A) HLA-A, HLA-B, (C) HLA-C, (D) HLA-DQA1,

More information

Epitope Specific CD8 + T Cell Responses Predict Spontaneous Control of HIV Replication

Epitope Specific CD8 + T Cell Responses Predict Spontaneous Control of HIV Replication Epitope Specific CD8 + T Cell Responses Predict Spontaneous Control of HIV Replication Florencia Pereyra, MD Partners AIDS Research Center Harvard Medical School Boston, MA Background HIV -1 elicits HLA

More information

On an individual level. Time since infection. NEJM, April HIV-1 evolution in response to immune selection pressures

On an individual level. Time since infection. NEJM, April HIV-1 evolution in response to immune selection pressures HIV-1 evolution in response to immune selection pressures BISC 441 guest lecture Zabrina Brumme, Ph.D. Assistant Professor, Faculty of Health Sciences Simon Fraser University http://www3.niaid.nih.gov/topics/hivaids/understanding/biology/structure.htm

More information

CS2220 Introduction to Computational Biology

CS2220 Introduction to Computational Biology CS2220 Introduction to Computational Biology WEEK 8: GENOME-WIDE ASSOCIATION STUDIES (GWAS) 1 Dr. Mengling FENG Institute for Infocomm Research Massachusetts Institute of Technology mfeng@mit.edu PLANS

More information

GENOME-WIDE ASSOCIATION STUDIES

GENOME-WIDE ASSOCIATION STUDIES GENOME-WIDE ASSOCIATION STUDIES SUCCESSES AND PITFALLS IBT 2012 Human Genetics & Molecular Medicine Zané Lombard IDENTIFYING DISEASE GENES??? Nature, 15 Feb 2001 Science, 16 Feb 2001 IDENTIFYING DISEASE

More information

2) Cases and controls were genotyped on different platforms. The comparability of the platforms should be discussed.

2) Cases and controls were genotyped on different platforms. The comparability of the platforms should be discussed. Reviewers' Comments: Reviewer #1 (Remarks to the Author) The manuscript titled 'Association of variations in HLA-class II and other loci with susceptibility to lung adenocarcinoma with EGFR mutation' evaluated

More information

Profiling HLA motifs by large scale peptide sequencing Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009

Profiling HLA motifs by large scale peptide sequencing Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009 Profiling HLA motifs by large scale peptide sequencing 2009 Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009 HLA Background The human leukocyte antigen system (HLA) is the

More information

Mina John Institute for Immunology and Infectious Diseases Royal Perth Hospital & Murdoch University Perth, Australia

Mina John Institute for Immunology and Infectious Diseases Royal Perth Hospital & Murdoch University Perth, Australia Mina John Institute for Immunology and Infectious Diseases Royal Perth Hospital & Murdoch University Perth, Australia AIDSvaccine conference, 14 th September 2011 IMGT HLA database July 2011 >5000 class

More information

Genetics and Genomics in Medicine Chapter 8 Questions

Genetics and Genomics in Medicine Chapter 8 Questions Genetics and Genomics in Medicine Chapter 8 Questions Linkage Analysis Question Question 8.1 Affected members of the pedigree above have an autosomal dominant disorder, and cytogenetic analyses using conventional

More information

5/2/18. After this class students should be able to: Stephanie Moon, Ph.D. - GWAS. How do we distinguish Mendelian from non-mendelian traits?

5/2/18. After this class students should be able to: Stephanie Moon, Ph.D. - GWAS. How do we distinguish Mendelian from non-mendelian traits? corebio II - genetics: WED 25 April 2018. 2018 Stephanie Moon, Ph.D. - GWAS After this class students should be able to: 1. Compare and contrast methods used to discover the genetic basis of traits or

More information

During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin,

During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin, ESM Methods Hyperinsulinemic-euglycemic clamp procedure During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin, Clayton, NC) was followed by a constant rate (60 mu m

More information

Frequency and Dynamics of Transmitted Polymorphisms and their Impact on Early Pathogenesis in Heterosexual Couples in Zambia

Frequency and Dynamics of Transmitted Polymorphisms and their Impact on Early Pathogenesis in Heterosexual Couples in Zambia Frequency and Dynamics of Transmitted Polymorphisms and their Impact on Early Pathogenesis in Heterosexual Couples in Zambia 8 th International Workshop on HIV Transmission Principles of Intervention Barcelona,

More information

New Enhancements: GWAS Workflows with SVS

New Enhancements: GWAS Workflows with SVS New Enhancements: GWAS Workflows with SVS August 9 th, 2017 Gabe Rudy VP Product & Engineering 20 most promising Biotech Technology Providers Top 10 Analytics Solution Providers Hype Cycle for Life sciences

More information

HIV acute infections and elite controllers- what can we learn?

HIV acute infections and elite controllers- what can we learn? HIV acute infections and elite controllers- what can we learn? Thumbi Ndung u, BVM, PhD KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) and HIV Pathogenesis Programme (HPP), Doris Duke

More information

Tolerance vs. Resistance of infectious diseases. Lea Mösch& Hanna Schiff

Tolerance vs. Resistance of infectious diseases. Lea Mösch& Hanna Schiff Tolerance vs. Resistance of infectious diseases Lea Mösch& Hanna Schiff Introduction Definitions: Tolerance: the ability to limit the disease severity induced by a given parasite burden Resistance: the

More information

HOW TO HIT THEM ALL IN ONE BLOW

HOW TO HIT THEM ALL IN ONE BLOW HOW TO HIT THEM ALL IN ONE BLOW HCV THE DISEASE More than 4 million Americans (1.3% of the U.S. population) and 170 million individuals in the world (3% worldwide) are infected with hepatitis C virus The

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary information S1 (table). Pathogen GWASs in NHGRI GWAS catalog (https://www.genome.gov/26525384) as of April 15, 2014 Disease or Pathogen Reference Pubmed ID minimum observed p-value # reported

More information

Introduction to the Impact of Resistance in Hepatitis C

Introduction to the Impact of Resistance in Hepatitis C Introduction to the Impact of Resistance in Hepatitis C Sponsored by AbbVie 2/1/2017 Presented by Sammy Saab, MD, MPH, FACG, AGAF, FAASLD February 1 st, 2017 1 AbbVie disclosures This is an Abbvie sponsored

More information

Antigen Presentation to T lymphocytes

Antigen Presentation to T lymphocytes Antigen Presentation to T lymphocytes Immunology 441 Lectures 6 & 7 Chapter 6 October 10 & 12, 2016 Jessica Hamerman jhamerman@benaroyaresearch.org Office hours by arrangement Antigen processing: How are

More information

The Role of Host: Genetic Variation

The Role of Host: Genetic Variation The Role of Host: Genetic Variation Patrick J. Stover, PhD The Janet and Gordon Lankton Professor of Nutrition Director, Division of Nutritional Sciences, Cornell University Dietary Requirements are Complex

More information

The Major Histocompatibility Complex (MHC)

The Major Histocompatibility Complex (MHC) The Major Histocompatibility Complex (MHC) An introduction to adaptive immune system before we discuss MHC B cells The main cells of adaptive immune system are: -B cells -T cells B cells: Recognize antigens

More information

Lecture 6. Burr BIO 4353/6345 HIV/AIDS. Tetramer staining of T cells (CTL s) Andrew McMichael seminar: Background

Lecture 6. Burr BIO 4353/6345 HIV/AIDS. Tetramer staining of T cells (CTL s) Andrew McMichael seminar: Background Lecture 6 Burr BIO 4353/6345 HIV/AIDS Andrew McMichael seminar: Background Tetramer staining of T cells (CTL s) 1. Vβ 19: There are 52 T cell receptor (TCR) Vβ gene segments in germ line DNA (See following

More information

Lack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han Chinese population

Lack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han Chinese population Lack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han Chinese population J. Zhu 1 *, F. He 2 *, D.D. Zhang 2 *, J.Y. Yang 2, J. Cheng 1, R. Wu 1, B. Gong 2, X.Q. Liu

More information

Title: Pinpointing resilience in Bipolar Disorder

Title: Pinpointing resilience in Bipolar Disorder Title: Pinpointing resilience in Bipolar Disorder 1. AIM OF THE RESEARCH AND BRIEF BACKGROUND Bipolar disorder (BD) is a mood disorder characterised by episodes of depression and mania. It ranks as one

More information

HOST-PARASITE INTERPLAY

HOST-PARASITE INTERPLAY HOST-PARASITE INTERPLAY Adriano Casulli EURLP, ISS (Rome, Italy) HOST-PARASITE INTERPLAY WP3 (parasite virulence vs human immunity) (Parasite) Task 3.1: Genotypic characterization Task 3.6: Transcriptome

More information

Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection

Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection Vaidya et al. Retrovirology 2013, 10:139 SHORT REPORT Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection Open Access Sagar A Vaidya 1,2, Hendrik Streeck 1,3,4, Noor Beckwith 1,

More information

DETECTION OF LOW FREQUENCY CXCR4-USING HIV-1 WITH ULTRA-DEEP PYROSEQUENCING. John Archer. Faculty of Life Sciences University of Manchester

DETECTION OF LOW FREQUENCY CXCR4-USING HIV-1 WITH ULTRA-DEEP PYROSEQUENCING. John Archer. Faculty of Life Sciences University of Manchester DETECTION OF LOW FREQUENCY CXCR4-USING HIV-1 WITH ULTRA-DEEP PYROSEQUENCING John Archer Faculty of Life Sciences University of Manchester HIV Dynamics and Evolution, 2008, Santa Fe, New Mexico. Overview

More information

THE IMPACT OF HLA CLASS I ON VIROLOGICAL OUTCOMES OF HBV

THE IMPACT OF HLA CLASS I ON VIROLOGICAL OUTCOMES OF HBV THE IMPACT OF HLA CLASS I ON VIROLOGICAL OUTCOMES OF HBV Philippa Matthews Consultant in Infectious Diseases & Microbiology SUPPRESSION CO-EVOLUTION ESCAPE Host factors associated with the clinical course

More information

This is the author s final accepted version.

This is the author s final accepted version. Ansari, M. A. et al. (2017) Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus. Nature Genetics, 49(5), pp. 666-673. (doi:10.1038/ng.3835)

More information

Rapid perforin upregulation directly ex vivo by CD8 + T cells is a defining characteristic of HIV elite controllers

Rapid perforin upregulation directly ex vivo by CD8 + T cells is a defining characteristic of HIV elite controllers Rapid perforin upregulation directly ex vivo by CD8 + T cells is a defining characteristic of HIV elite controllers Adam R. Hersperger Department of Microbiology University of Pennsylvania Evidence for

More information

Viral and Host Factors in Vulvar Disease DR MICHELLE ETHERSON 26 TH OF APRIL 2016

Viral and Host Factors in Vulvar Disease DR MICHELLE ETHERSON 26 TH OF APRIL 2016 Viral and Host Factors in Vulvar Disease DR MICHELLE ETHERSON 26 TH OF APRIL 2016 Human Papillomavirus (HPV) Small non-enveloped Double stranded DNA Virus Genome 8000 basepairs 8 coding genes, Early (E)

More information

The omics approach in measuring the double burden of malnutrition

The omics approach in measuring the double burden of malnutrition IAEA Headquarter, Vienna, Austria, 3-5 October 2017 Joint IAEA-WHO-UNICEF workshop on analysis of biological pathways to better understand the double burden of malnutrition and to inform action planning

More information

Introduction to Genetics and Genomics

Introduction to Genetics and Genomics 2016 Introduction to enetics and enomics 3. ssociation Studies ggibson.gt@gmail.com http://www.cig.gatech.edu Outline eneral overview of association studies Sample results hree steps to WS: primary scan,

More information

Self reported ethnicity

Self reported ethnicity Self reported ethnicity Supplementary Figure 1 Ancestry stratifies patterns of human genetic variations. PCA plots (1 st, 2 nd and 3 rd components) estimated from human genotypes. Individuals are coloured

More information

Drug Metabolism Disposition

Drug Metabolism Disposition Drug Metabolism Disposition The CYP2C19 intron 2 branch point SNP is the ancestral polymorphism contributing to the poor metabolizer phenotype in livers with CYP2C19*35 and CYP2C19*2 alleles Amarjit S.

More information

Mapping evolutionary pathways of HIV-1 drug resistance using conditional selection pressure. Christopher Lee, UCLA

Mapping evolutionary pathways of HIV-1 drug resistance using conditional selection pressure. Christopher Lee, UCLA Mapping evolutionary pathways of HIV-1 drug resistance using conditional selection pressure Christopher Lee, UCLA HIV-1 Protease and RT: anti-retroviral drug targets protease RT Protease: responsible for

More information

Supplementary Materials

Supplementary Materials 1 Supplementary Materials Rotger et al. Table S1A: Demographic characteristics of study participants. VNP RP EC CP (n=6) (n=66) (n=9) (n=5) Male gender, n(%) 5 (83) 54 (82) 5 (56) 3 (60) White ethnicity,

More information

White Paper Guidelines on Vetting Genetic Associations

White Paper Guidelines on Vetting Genetic Associations White Paper 23-03 Guidelines on Vetting Genetic Associations Authors: Andro Hsu Brian Naughton Shirley Wu Created: November 14, 2007 Revised: February 14, 2008 Revised: June 10, 2010 (see end of document

More information

The Genetic Epidemiology of Rheumatoid Arthritis. Lindsey A. Criswell AURA meeting, 2016

The Genetic Epidemiology of Rheumatoid Arthritis. Lindsey A. Criswell AURA meeting, 2016 The Genetic Epidemiology of Rheumatoid Arthritis Lindsey A. Criswell AURA meeting, 2016 Overview Recent successes in gene identification genome wide association studies (GWAS) clues to etiologic pathways

More information

10/19/2017. How Nutritional Genomics Affects You in Nutrition Research and Practice Joyanna Hansen, PhD, RD & Kristin Guertin, PhD, MPH

10/19/2017. How Nutritional Genomics Affects You in Nutrition Research and Practice Joyanna Hansen, PhD, RD & Kristin Guertin, PhD, MPH Disclosures Joyanna Hansen How Affects You in Nutrition Research and Practice Joyanna Hansen, PhD, RD & Kristin Guertin, PhD, MPH Consultant Nutricia North America Research Support Academy of Nutrition

More information

Genes, Diseases and Lisa How an advanced ICT research infrastructure contributes to our health

Genes, Diseases and Lisa How an advanced ICT research infrastructure contributes to our health Genes, Diseases and Lisa How an advanced ICT research infrastructure contributes to our health Danielle Posthuma Center for Neurogenomics and Cognitive Research VU Amsterdam Most human diseases are heritable

More information

How HIV Causes Disease Prof. Bruce D. Walker

How HIV Causes Disease Prof. Bruce D. Walker How HIV Causes Disease Howard Hughes Medical Institute Massachusetts General Hospital Harvard Medical School 1 The global AIDS crisis 60 million infections 20 million deaths 2 3 The screen versions of

More information

Compound heterozygosity Yurii S. Aulchenko yurii [dot] aulchenko [at] gmail [dot] com. Thursday, April 11, 13

Compound heterozygosity Yurii S. Aulchenko yurii [dot] aulchenko [at] gmail [dot] com. Thursday, April 11, 13 Compound heterozygosity Yurii S. Aulchenko yurii [dot] aulchenko [at] gmail [dot] com 1 Outline Recessive model Examples of Compound Heterozygosity Compound Double Heterozygosity (CDH) test 2 Recessive

More information

Elevated CD4+/CD8+ Ratio in HIV Elite Controller

Elevated CD4+/CD8+ Ratio in HIV Elite Controller Elevated / Ratio in HIV Elite Controller Joseph Carnevale, BA 1,2 ; Timothy Flanigan, MD 2,3 1 Fordham University, New York, NY 2 Brown University Alpert Medical School, Providence, RI 3 Division of Infectious

More information

The Foundations of Personalized Medicine

The Foundations of Personalized Medicine The Foundations of Personalized Medicine Jeremy M. Berg Pittsburgh Foundation Professor and Director, Institute for Personalized Medicine University of Pittsburgh Personalized Medicine Physicians have

More information

Large-scale identity-by-descent mapping discovers rare haplotypes of large effect. Suyash Shringarpure 23andMe, Inc. ASHG 2017

Large-scale identity-by-descent mapping discovers rare haplotypes of large effect. Suyash Shringarpure 23andMe, Inc. ASHG 2017 Large-scale identity-by-descent mapping discovers rare haplotypes of large effect Suyash Shringarpure 23andMe, Inc. ASHG 2017 1 Why care about rare variants of large effect? Months from randomization 2

More information

The genetics of complex traits Amazing progress (much by ppl in this room)

The genetics of complex traits Amazing progress (much by ppl in this room) The genetics of complex traits Amazing progress (much by ppl in this room) Nick Martin Queensland Institute of Medical Research Brisbane Boulder workshop March 11, 2016 Genetic Epidemiology: Stages of

More information

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder)

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) September 14, 2012 Chun Xu M.D, M.Sc, Ph.D. Assistant professor Texas Tech University Health Sciences Center Paul

More information

HIV-1 acute infection: evidence for selection?

HIV-1 acute infection: evidence for selection? HIV-1 acute infection: evidence for selection? ROLLAND Morgane University of Washington Cohort & data S6 S5 T4 S4 T2 S2 T1 S1 S7 T3 DPS (days post symptoms) 3 (Fiebig I) 7 (Fiebig I) 13 (Fiebig V) 14 (Fiebig

More information

Supplementary Online Content

Supplementary Online Content Supplementary Online Content Hartwig FP, Borges MC, Lessa Horta B, Bowden J, Davey Smith G. Inflammatory biomarkers and risk of schizophrenia: a 2-sample mendelian randomization study. JAMA Psychiatry.

More information

Selection of epitope-based vaccine targets of HCV genotype 1 of Asian origin: a systematic in silico approach

Selection of epitope-based vaccine targets of HCV genotype 1 of Asian origin: a systematic in silico approach www.bioinformation.net Hypothesis Volume 8(20) Selection of epitope-based vaccine targets of HCV genotype 1 of Asian origin: a systematic in silico approach Abida Shehzadi 1 *, Shahid Ur Rehman 1, 2 &

More information

Mechanisms of antagonism of HIVspecific CD4+ T cell responses BSRI

Mechanisms of antagonism of HIVspecific CD4+ T cell responses BSRI Mechanisms of antagonism of HIVspecific CD4+ T cell responses BSRI Problems Virus escape from immune recognition Antagonism of T cell responses Peptide-MHC-TCR interaction T cell antagonism Variants of

More information

Association mapping (qualitative) Association scan, quantitative. Office hours Wednesday 3-4pm 304A Stanley Hall. Association scan, qualitative

Association mapping (qualitative) Association scan, quantitative. Office hours Wednesday 3-4pm 304A Stanley Hall. Association scan, qualitative Association mapping (qualitative) Office hours Wednesday 3-4pm 304A Stanley Hall Fig. 11.26 Association scan, qualitative Association scan, quantitative osteoarthritis controls χ 2 test C s G s 141 47

More information

Prevention of infection 2 : immunisation. How infection influences the host : viruses. Peter

Prevention of infection 2 : immunisation. How infection influences the host : viruses. Peter Prevention of infection 2 : immunisation How infection influences the host : viruses Peter Balfe, p.balfe@bham.ac.uk @pbalfeuk Let s have some LO s just for fun 1. Define the Immune response to viruses,

More information

Rapid intrahost evolution of human cytomegalovirus is shaped by demography and positive selection

Rapid intrahost evolution of human cytomegalovirus is shaped by demography and positive selection University of Massachusetts Medical School escholarship@umms Open Access Articles Open Access Publications by UMMS Authors 9-26-2013 Rapid intrahost evolution of human cytomegalovirus is shaped by demography

More information

Supplementary Figures

Supplementary Figures Supplementary Figures Supplementary Fig 1. Comparison of sub-samples on the first two principal components of genetic variation. TheBritishsampleisplottedwithredpoints.The sub-samples of the diverse sample

More information

Clinical utility of NGS for the detection of HIV and HCV resistance

Clinical utility of NGS for the detection of HIV and HCV resistance 18 th Annual Resistance and Antiviral Therapy Meeting v Professor Janke Schinkel Academic Medical Centre, Amsterdam, The Netherlands Thursday 18 September 2014, Royal College of Physicians, London Clinical

More information

Fondation Merieux J Craig Venter Institute Bioinformatics Workshop. December 5 8, 2017

Fondation Merieux J Craig Venter Institute Bioinformatics Workshop. December 5 8, 2017 Fondation Merieux J Craig Venter Institute Bioinformatics Workshop December 5 8, 2017 Module 5: Comparative Genomics Analysis Outline Definition of comparative genomics Applications in studying human pathogens

More information

Host genotypes, inflammatory response and outcome of TBM Vietnam

Host genotypes, inflammatory response and outcome of TBM Vietnam Host genotypes, inflammatory response and outcome of TBM Vietnam Nguyen T.T. Thuong Oxford University Clinical Research Unit Ho Chi Minh City, Vietnam Tuberculous Meningitis (TBM) Diagnosis remains difficult

More information

The Immune Epitope Database Analysis Resource: MHC class I peptide binding predictions. Edita Karosiene, Ph.D.

The Immune Epitope Database Analysis Resource: MHC class I peptide binding predictions. Edita Karosiene, Ph.D. The Immune Epitope Database Analysis Resource: MHC class I peptide binding predictions Edita Karosiene, Ph.D. edita@liai.org IEDB Workshop October 29, 2015 Outline Introduction MHC-I peptide binding prediction

More information

Section D. Identification of serotype-specific amino acid positions in DENV NS1. Objective

Section D. Identification of serotype-specific amino acid positions in DENV NS1. Objective Section D. Identification of serotype-specific amino acid positions in DENV NS1 Objective Upon completion of this exercise, you will be able to use the Virus Pathogen Resource (ViPR; http://www.viprbrc.org/)

More information

Significance of the MHC

Significance of the MHC CHAPTER 7 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ

More information

Introduction to the Genetics of Complex Disease

Introduction to the Genetics of Complex Disease Introduction to the Genetics of Complex Disease Jeremiah M. Scharf, MD, PhD Departments of Neurology, Psychiatry and Center for Human Genetic Research Massachusetts General Hospital Breakthroughs in Genome

More information

Nature Genetics: doi: /ng Supplementary Figure 1

Nature Genetics: doi: /ng Supplementary Figure 1 Supplementary Figure 1 Illustrative example of ptdt using height The expected value of a child s polygenic risk score (PRS) for a trait is the average of maternal and paternal PRS values. For example,

More information

Copy Number Variation of KIR Genes Influences HIV-1 Control

Copy Number Variation of KIR Genes Influences HIV-1 Control Copy Number Variation of KIR Genes Influences HIV-1 Control Kimberly Pelak 1., Anna C. Need 1., Jacques Fellay 1,2., Kevin V. Shianna 1, Sheng Feng 3, Thomas J. Urban 1, Dongliang Ge 1, Andrea De Luca

More information

Part I Tuberculosis (TB): the Once and Future Plague

Part I Tuberculosis (TB): the Once and Future Plague Part I Tuberculosis (TB): the Once and Future Plague John D. McKinney Global Health Institute School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL) The American Society for Cell Biology

More information

Vaccine Design: A Statisticans Overview

Vaccine Design: A Statisticans Overview GoBack : A Statisticans Overview. Surajit Ray sray@samsi.info Surajit Ray Samsi PostDoc Seminar: Nov 2: 2004 - slide #1 The Chinese are credited with making the observation that deliberately infecting

More information

Identification of heritable genetic risk factors for bladder cancer through genome-wide association studies (GWAS)

Identification of heritable genetic risk factors for bladder cancer through genome-wide association studies (GWAS) BCAN 2014 August 9, 2014 Identification of heritable genetic risk factors for bladder cancer through genome-wide association studies (GWAS) Ludmila Prokunina-Olsson, PhD Investigator Laboratory of Translational

More information

Immunodeficiency. (2 of 2)

Immunodeficiency. (2 of 2) Immunodeficiency (2 of 2) Acquired (secondary) immunodeficiencies More common Many causes such as therapy, cancer, sarcoidosis, malnutrition, infection & renal disease The most common of which is therapy-related

More information

Quantitative genetics: traits controlled by alleles at many loci

Quantitative genetics: traits controlled by alleles at many loci Quantitative genetics: traits controlled by alleles at many loci Human phenotypic adaptations and diseases commonly involve the effects of many genes, each will small effect Quantitative genetics allows

More information

Use of Genetics to Inform Drug Development of a Novel Treatment for Schizophrenia

Use of Genetics to Inform Drug Development of a Novel Treatment for Schizophrenia Use of Genetics to Inform Drug Development of a Novel Treatment for Schizophrenia March 21, 2012 Institute of Medicine: New Paradigms in Drug Discovery Workshop Laura K. Nisenbaum, PhD Translational Medicine,

More information

Genetics of COPD Prof. Ian P Hall

Genetics of COPD Prof. Ian P Hall Genetics of COPD 1 Prof. Ian P. Hall Dean, Faculty of Medicine and Health Sciences The University of Nottingham Medical School Ian.Hall@nottingham.ac.uk Chronic obstructive pulmonary disease (COPD) 900,000

More information

Epitope discovery. Using predicted MHC binding CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS

Epitope discovery. Using predicted MHC binding CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Epitope discovery Using predicted MHC binding SARS corona virus The 2003 outbreak The disease Lung Pathology Inflammatory exudation in alveoli and interstitial spaces Monocytic and lymphocytic infiltration

More information

The major histocompatibility complex (MHC) is a group of genes that governs tumor and tissue transplantation between individuals of a species.

The major histocompatibility complex (MHC) is a group of genes that governs tumor and tissue transplantation between individuals of a species. Immunology Dr. John J. Haddad Chapter 7 Major Histocompatibility Complex The major histocompatibility complex (MHC) is a group of genes that governs tumor and tissue transplantation between individuals

More information

HEATHER ANN PRENTICE ELIZABETH E. BROWN, COMMITTEE CHAIR RICHARD A. KASLOW JIANMING TANG NICHOLAS M. PAJEWSKI KUI ZHANG A DISSERTATION

HEATHER ANN PRENTICE ELIZABETH E. BROWN, COMMITTEE CHAIR RICHARD A. KASLOW JIANMING TANG NICHOLAS M. PAJEWSKI KUI ZHANG A DISSERTATION HIGH DENSITY GENOTYPING FOR IMMUNOGENETIC POLYMORPHISMS ASSOCIATED WITH TRANSMISSION AND CONTROL OF HIV-1 INFECTION IN ZAMBIAN HETEROSEXUAL SERODISCORDANT COUPLES by HEATHER ANN PRENTICE ELIZABETH E. BROWN,

More information

# For the GWAS stage, B-cell NHL cases which small numbers (N<20) were excluded from analysis.

# For the GWAS stage, B-cell NHL cases which small numbers (N<20) were excluded from analysis. Supplementary Table 1a. Subtype Breakdown of all analyzed samples Stage GWAS Singapore Validation 1 Guangzhou Validation 2 Guangzhou Validation 3 Beijing Total No. of B-Cell Cases 253 # 168^ 294^ 713^

More information

Lecture 20. Disease Genetics

Lecture 20. Disease Genetics Lecture 20. Disease Genetics Michael Schatz April 12 2018 JHU 600.749: Applied Comparative Genomics Part 1: Pre-genome Era Sickle Cell Anaemia Sickle-cell anaemia (SCA) is an abnormality in the oxygen-carrying

More information

Figure S1. Alignment of predicted amino acid sequences of KIR3DH alleles identified in 8

Figure S1. Alignment of predicted amino acid sequences of KIR3DH alleles identified in 8 Supporting Information Figure S1. Alignment of predicted amino acid sequences of KIR3DH alleles identified in 8 unrelated rhesus monkeys. KIR3DH alleles, expressed by CD14 CD16 + NK cells that were isolated

More information

Using Network Flow to Bridge the Gap between Genotype and Phenotype. Teresa Przytycka NIH / NLM / NCBI

Using Network Flow to Bridge the Gap between Genotype and Phenotype. Teresa Przytycka NIH / NLM / NCBI Using Network Flow to Bridge the Gap between Genotype and Phenotype Teresa Przytycka NIH / NLM / NCBI Journal Wisla (1902) Picture from a local fare in Lublin, Poland Genotypes Phenotypes Journal Wisla

More information

IMMUNOINFORMATICS: Bioinformatics Challenges in Immunology

IMMUNOINFORMATICS: Bioinformatics Challenges in Immunology Bioinformatics 1 -- Lecture 22 IMMUNOINFORMATICS: Bioinformatics Challenges in Immunology Most slides courtesy of Julia Ponomarenko, San Diego Supercomputer Center or Oliver Kohlbacher, WSI/ZBIT, Eberhard-Karls-

More information

Etiology of Chronic Diseases. Complex Diseases Genes and Environment Initiative

Etiology of Chronic Diseases. Complex Diseases Genes and Environment Initiative Etiology of Chronic Diseases Complex Diseases Genes and Environment Initiative Top 10 Causes of Mortality in 2003 Death Rate per 100,000 Heart disease...232 Cancer...190 Cerebrovascular disease....54 Chronic

More information

NEXT GENERATION SEQUENCING. R. Piazza (MD, PhD) Dept. of Medicine and Surgery, University of Milano-Bicocca

NEXT GENERATION SEQUENCING. R. Piazza (MD, PhD) Dept. of Medicine and Surgery, University of Milano-Bicocca NEXT GENERATION SEQUENCING R. Piazza (MD, PhD) Dept. of Medicine and Surgery, University of Milano-Bicocca SANGER SEQUENCING 5 3 3 5 + Capillary Electrophoresis DNA NEXT GENERATION SEQUENCING SOLEXA-ILLUMINA

More information

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review Mémoire de Maîtrise en médecine No 1488 Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review Student Benoît Delabays Tutor PD Dr Pierre-Yves Bochud Service des maladies infectieuses Département

More information

Co-evolution of host and pathogen: HIV as a model. Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL

Co-evolution of host and pathogen: HIV as a model. Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL Co-evolution of host and pathogen: HIV as a model Can Keşmir Theoretical Biology/Bioinformatics Utrecht University, NL c.kesmir@bio.uu.nl Outline Does HIV adapt to monomorphic human molecules? Polymorphic

More information

An Introduction to Quantitative Genetics I. Heather A Lawson Advanced Genetics Spring2018

An Introduction to Quantitative Genetics I. Heather A Lawson Advanced Genetics Spring2018 An Introduction to Quantitative Genetics I Heather A Lawson Advanced Genetics Spring2018 Outline What is Quantitative Genetics? Genotypic Values and Genetic Effects Heritability Linkage Disequilibrium

More information

Massoud Houshmand National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

Massoud Houshmand National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran QUID 2017, pp. 669-673, Special Issue N 1- ISSN: 1692-343X, Medellín-Colombia NON-GENE REGION AND INFLUENCES TUMOR CHARACTERISTICS BY LOW-RISK ALLELES IN BREAST CANCER (Recibido el 21-06-2017. Aprobado

More information

Example HLA-B and abacavir. Roujeau 2014

Example HLA-B and abacavir. Roujeau 2014 Example HLA-B and abacavir Roujeau 2014 FDA requires testing for abacavir Treatment with abacavir is generally well tolerated, but 5% of the patients experience hypersensitivity reactions that can be life

More information

Paola Nicoletti, Harshad Devarbhavi, Ashish Goel, CE Eapen, Radha Venkatesan, Jane I Grove, Ann K Daly and Guruprasad P. Aithal

Paola Nicoletti, Harshad Devarbhavi, Ashish Goel, CE Eapen, Radha Venkatesan, Jane I Grove, Ann K Daly and Guruprasad P. Aithal Genome-wide association study (GWAS) to identify genetic risk factors that increase susceptibility to antituberculosis drug-induced liver injury (ATDILI) Paola Nicoletti, Harshad Devarbhavi, Ashish Goel,

More information

Citation for published version (APA): Von Eije, K. J. (2009). RNAi based gene therapy for HIV-1, from bench to bedside

Citation for published version (APA): Von Eije, K. J. (2009). RNAi based gene therapy for HIV-1, from bench to bedside UvA-DARE (Digital Academic Repository) RNAi based gene therapy for HIV-1, from bench to bedside Von Eije, K.J. Link to publication Citation for published version (APA): Von Eije, K. J. (2009). RNAi based

More information

GWAS mega-analysis. Speakers: Michael Metzker, Douglas Blackwood, Andrew Feinberg, Nicholas Schork, Benjamin Pickard

GWAS mega-analysis. Speakers: Michael Metzker, Douglas Blackwood, Andrew Feinberg, Nicholas Schork, Benjamin Pickard Workshop: A stage for shaping the next generation of genome-wide association studies (GWAS). GWAS mega-analysis for complex diseases Part of the International Conference on Systems Biology (ICSB2010) The

More information

DIRECT IDENTIFICATION OF NEO-EPITOPES IN TUMOR TISSUE

DIRECT IDENTIFICATION OF NEO-EPITOPES IN TUMOR TISSUE DIRECT IDENTIFICATION OF NEO-EPITOPES IN TUMOR TISSUE Eustache Paramithiotis PhD Vice President, Biomarker Discovery & Diagnostics 17 March 2016 PEPTIDE PRESENTATION BY MHC MHC I Antigen presentation by

More information

Structural Variation and Medical Genomics

Structural Variation and Medical Genomics Structural Variation and Medical Genomics Andrew King Department of Biomedical Informatics July 8, 2014 You already know about small scale genetic mutations Single nucleotide polymorphism (SNPs) Deletions,

More information

Dependence Syndrome (Edwards and Gross, 1976)

Dependence Syndrome (Edwards and Gross, 1976) Genetic Research on Alcohol and Drugs: From Abstinence to Dependence Ethics of Genetics in Research May 19, 2006 Deborah Hasin, Ph.D. Columbia University New York State Psychiatric Institute Dependence

More information

Biology 2C03: Genetics What is a Gene?

Biology 2C03: Genetics What is a Gene? Biology 2C03: Genetics What is a Gene? September 9 th, 2013 Model Organisms - E. coli - Yeast - Worms - Arabodopsis - Fruitflie - Mouse What is a Gene? - Define, recognize, describe and apply Mendel s

More information

BST227 Introduction to Statistical Genetics. Lecture 4: Introduction to linkage and association analysis

BST227 Introduction to Statistical Genetics. Lecture 4: Introduction to linkage and association analysis BST227 Introduction to Statistical Genetics Lecture 4: Introduction to linkage and association analysis 1 Housekeeping Homework #1 due today Homework #2 posted (due Monday) Lab at 5:30PM today (FXB G13)

More information

Correspondence should be addressed to Carmen Rodríguez-Sainz;

Correspondence should be addressed to Carmen Rodríguez-Sainz; Hindawi Immunology Research Volume 2017, Article ID 8689313, 7 pages https://doi.org/10.1155/2017/8689313 Research Article Impact of the Polymorphism rs9264942 near the HLA-C Gene on HIV-1 DNA Reservoirs

More information

Heritability and genetic correlations explained by common SNPs for MetS traits. Shashaank Vattikuti, Juen Guo and Carson Chow LBM/NIDDK

Heritability and genetic correlations explained by common SNPs for MetS traits. Shashaank Vattikuti, Juen Guo and Carson Chow LBM/NIDDK Heritability and genetic correlations explained by common SNPs for MetS traits Shashaank Vattikuti, Juen Guo and Carson Chow LBM/NIDDK The Genomewide Association Study. Manolio TA. N Engl J Med 2010;363:166-176.

More information

Introduction to linkage and family based designs to study the genetic epidemiology of complex traits. Harold Snieder

Introduction to linkage and family based designs to study the genetic epidemiology of complex traits. Harold Snieder Introduction to linkage and family based designs to study the genetic epidemiology of complex traits Harold Snieder Overview of presentation Designs: population vs. family based Mendelian vs. complex diseases/traits

More information

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Basic Immunology Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Molecular structure of MHC, subclasses, genetics, functions. Antigen presentation and MHC restriction.

More information

studies would be large enough to have the power to correctly assess the joint effect of multiple risk factors.

studies would be large enough to have the power to correctly assess the joint effect of multiple risk factors. Collaborative Research: examples of multicentre studies The need for an organization with a worldwide mandate to promote and lead international collaborations in cancer research was one of the main driving

More information