17th International HLA and Immunogenetics Workshop http://ihiws.org My WordPress Blog Tue, 03 Oct 2017 22:08:22 +0000 en-US hourly 1 https://wordpress.org/?v=4.9.2 NGS of Full-length HLA genes http://ihiws.org/ngs-of-full-length-hla-genes/ http://ihiws.org/ngs-of-full-length-hla-genes/#comments Mon, 29 Sep 2014 06:33:51 +0000 http://localhost/IHIWS/?p=52 The HLA genes are the most polymorphic loci in the human genome; over 12,000 genetic variants (alleles) have been identified at 19 HLA genes, with some individual genes displaying several thousand alleles. The allelic and structural variation that characterizes these genes pose extreme challenges for routine genotyping of these genetic loci; this variation cannot be characterized by a few SNPs, and the high level of polymorphism confounds de novo sequence assembly efforts. Until recently, HLA genotyping has been accomplished using a variety of PCR-based approaches involving sequence-specific oligonucleotide probe (SSOP) hybridization and/or Sanger sequencing of 400-600 base pair amplicons. These... Read More]]> The HLA genes are the most polymorphic loci in the human genome; over 12,000 genetic variants (alleles) have been identified at 19 HLA genes, with some individual genes displaying several thousand alleles. The allelic and structural variation that characterizes these genes pose extreme challenges for routine genotyping of these genetic loci; this variation cannot be characterized by a few SNPs, and the high level of polymorphism confounds de novo sequence assembly efforts. Until recently, HLA genotyping has been accomplished using a variety of PCR-based approaches involving sequence-specific oligonucleotide probe (SSOP) hybridization and/or Sanger sequencing of 400-600 base pair amplicons. These methods do not readily allow the establishment of chromosomal-phase between assessed sequence features, which results in considerable ambiguity regarding an HLA genotype.

Next generation sequencing (NGS) methods are now being applied for HLA genotyping with great success. These methods apply a variety of single-molecule sequencing approaches to accomplish extensive phasing across genes, minimizing genotyping ambiguity, accelerating polymorphism discovery, and improving our understanding of allelic diversity. The inherent high-throughput nature of NGS has a broad potential for therapeutic and diagnostic applications. However, a wide variety of NGS platforms and methodologies are available, and their relative strengths and shortcomings for Histocompatibility and Immunogenetics (H&I) research applications remain unexplored.

The goal of the 17th International HLA and Immunogenetics Workshop is to advance the fields of H&I research through the application of NGS technologies, and to advance the development of NGS technologies tailored to meet the needs of the H&I community.

Although the HLA field has a well-defined nomenclature system, and well-curated reference sequence database, significant gaps in sequence coverage remain for the majority of HLA alleles, as these variants have been defined on the basis of partial gene sequence. In the absence of complete reference sequences, sequence datasets cannot be leveraged to the greatest extent possible; phasing of raw sequence data will suffer, resulting in erroneous or ambiguous genotype assignments, and variation in the genotyping results returned by different NGS typing approaches.


 Goals

1.  To complete the sequence of all HLA alleles of the reference cell lines from the 13th IHIWS.
2.  To perform HLA genotyping of 10,000 quartet families of varied ancestry, utilizing at least one NGS method

Activities

1. Cloning or isolated amplification and nucleotide sequencing of all HLA alleles of the reference cell lines from the 13th IHIWS

Different methodological approaches for cloning and nucleotide sequencing are accepted. DNA or cells corresponding to cell lines from the 13th IHIWS will be distributed to laboratories interested in participating in this study. A variety of analytical methods corresponding to specific sequencing platforms will be applied for determining consensus sequences. These sequences will be deposited in GenBank and will be publicly available when validated and approved by the steering committee.

2. HLA Typing by Next Generation Sequencing Methodologies

The primary focus of the 17th IHWS will be Next Generation Sequencing (NGS) of classical HLA and the KIR genes with the aim of advancing the field by providing deep sequencing of all exons, all introns, and the 5′ and 3′ UTRs of the classical HLA genes. We would like to invite investigators, institutions and laboratories to participate in this component by performing NGS based testing and/or analysis of NGS data using various NGS platforms (including and not restricted to Illumina, Ion Torrent, Roche 454, PacBio) and software analysis packages that have already been validated for HLA typing. Other NGS typing approaches are encouraged for participation.

Investigators can participate in this component by submission of DNA specimens to be tested by a second laboratory or by HLA NGS typing of locally collected specimens. All eligible specimens to be included in the study should include appropriate informed consent and be approved for participation by the local Institutional Review Board.

All participant investigators are invited and encouraged to participate in the data analysis and preparation of manuscripts.

The laboratories performing testing will submit sequencing and genotype results electronically. There will be centralized data collection; this data may be distributed to other investigators that may utilize different software packages.

The samples to be included in the studies should be from at least four individuals from a single biological family. It is encouraged to include families previously typed for some HLA loci. Ideally parents and all offspring should be included in the study.

Through the analysis of the segregation of alleles in families, we will be able to determine unambiguous HLA allelic haplotypes; we propose to analyze informative quartets in which each haplotype is probed in two different family members, paired with different haplotypes. The proposed studies will render high quality sequence data that will provide the community with a large-scale database of complete genomic segments of the HLA genes. In addition we plan to perform SNP testing in these families. Analysis of the total genomic region, including both coding and non-coding regions with different selective pressures, will help to clarify the evolution of the HLA system.

Links for participation will be found on this page in the near future. We anticipate starting participation and data collection in January 2015.

HLA Typing for NGS – Pilot Project

We conducted a pilot project in which we will compare HLA typing results obtained by different NGS platforms utilizing different sets of primers with variable coverage. We will examine performance by the different methods and will investigate ways of transmitting results capturing coverage information and nuances specific for each platform/reagent combination.

The testing of a common set of reference samples by several sets of platforms/reagent combinations will allow us to:

  • evaluate the performance of each platform/reagent combination.
  • identify limitations/nuances specific for each platform/reagent.
  • evaluate software analyses packages utilized to analyze sequences and assign genotypes and possible biases of the corresponding algorithms.
  • evaluate ways of transmitting and capturing data that can be stored in the appropriate format to be re-analyzed in the future and genotype assignments obtained by different platform/reagent sets can be compared.

Because the HLA sequence databases change significantly in short periods of time with the identification of new alleles and the extension of sequences in incompletely covered alleles, the ability to capture data for re-analysis of genotype assignments over time is crucial to understand HLA diversity and to maintain accurate genotype assignments.

This pilot study is being conducted in 15 international laboratories performing HLA typing using various NGS platform/reagent combinations. Each participant lab will test a set of fifty blinded DNA samples which have been collected in previous S or cell lines that have been permanently stored and can be distributed without restrictions for future use. These cell lines were typed for some but not all HLA loci by standard Sanger sequencing methods. The laboratories performing testing are submitting sequencing and genotype results electronically. The centralized data collection will be distributed to other investigators that may utilize different software packages.

Cloning and sequencing of classical HLA loci in the reference samples has been and is being performed. The cloning and sequencing results will serve as an unambiguous reference of the evaluation of each platform/reagent/software combination used. In addition the cloning and sequencing will contribute to the necessary completion of sequences of common alleles with the resulting enhancements in unambiguous HLA genotype assignments.

Component Leaders: Marcelo Fernandez-Viña PhD, Steven J. Mack PhD
Liaison: Harriet Noreen CHS

 

→ Next Article: Preliminary Results of the Pilot Study

Read More

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Component: NGS of full length HLA genes: Preliminary results of the Pilot Study http://ihiws.org/component-ngs-of-full-length-hla-genes-preliminary-results-of-the-pilot-study/ http://ihiws.org/component-ngs-of-full-length-hla-genes-preliminary-results-of-the-pilot-study/#respond Tue, 08 Dec 2015 19:24:55 +0000 http://ihiws.org/?p=922 Lisa E Creary1, Steven J Mack2 and Marcelo Fernandez-Vina1
1Department of Pathology, Stanford Blood Center
2Children’s Hospital Oakland Research Institute

Overview

The ultimate goal of the 17th International HLA and Immunogenetics Workshop (IHIW) is to advance the fields of Histocompatibility and Immunogenetics (H & I) research through the application of Next-Generation Sequencing (NGS) technologies for HLA and KIR genotyping, and to advance the development of NGS technologies tailored to meet the needs of the H & I community.

In 2014, we initiated an international multi-center pilot study in order to assess the performance of various NGS protocols, platforms,... Read More]]> Lisa E Creary1, Steven J Mack2 and Marcelo Fernandez-Vina1
1
Department of Pathology, Stanford Blood Center
2Children’s Hospital Oakland Research Institute

Overview

The ultimate goal of the 17th International HLA and Immunogenetics Workshop (IHIW) is to advance the fields of Histocompatibility and Immunogenetics (H & I) research through the application of Next-Generation Sequencing (NGS) technologies for HLA and KIR genotyping, and to advance the development of NGS technologies tailored to meet the needs of the H & I community.

In 2014, we initiated an international multi-center pilot study in order to assess the performance of various NGS protocols, platforms, and software for full gene typing of classical class I (HLA-A, -B, -C) and class II (HLA-DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4, -DRB5) genes.

The specific aims of this study were four-fold:

  • Evaluate the performance of different NGS protocols and platforms, and identify the limitations/nuances specific to each method.
  • Evaluate software programs for analysis of sequence data and assignment of HLA genotypes.
  • Inform the design of optimized methods for the exchange and storage of NGS data. A goal of the workshop is to store HLA genotyping data in a format for reanalysis. This format should allow for simple and systematic examination and comparison of genotypes obtained by different protocols and platforms.
  • Clone and sequence all class I and class II alleles in a quality control (QC) reference panel. These results will constitute an unambiguous reference for the evaluation of NGS reagent/platform combinations. In addition, these reference data will contribute to the necessary completion of full-gene sequences for common alleles and aid in identifying novel alleles resulting in unambiguous HLA genotypes.

 

Methods

We initially conducted a survey of twenty-five interested laboratories, using a questionnaire to gather information about the number and type of HLA genes that participants were able to sequence, NGS protocol and instrumentation used, software analysis packages (e.g. commercial or in-house) used, and type of output file formats. Fifty blinded QC cell line-derived genomic DNA samples, supplied by the Fred Hutchinson Cancer Research Center, Seattle, WA (http://www.ihwg.org) and collected in previous IHIWs were distributed to seventeen laboratories. These samples were genotyped by fifteen laboratories, or groups within the same laboratory applying different platforms and/or reagents, located worldwide (Table 1). The QC panel was selected to represent a wide range of HLA allele families and to include CWD alleles, rare alleles, null alleles, and samples homozygous for at least one locus. The QC cell lines had been typed previously by Sanger sequence Based Typing (SBT), sequence-specific primers (SSP), sequence-specific oligonucleotide (SSO) probes, serological and cellular methods for some but not all HLA genes. One of the fifteen laboratories also cloned and determined the nucleotide sequences for the majority of the HLA alleles of the QC panel. Genotype results were collated over a period of 10 months. Primary sequencing data (e.g. FASTQ files) were also collected from five laboratories.

 

Table 1. NGS HLA Pilot Study participating laboratories
Laboratory
Antony Nolan, London, UK
BFR, Beijing, China
GenDx, Utrecht, Netherlands
Georgetown University, Washington DC, USA
H&I Laboratory, Nantes, France
Royal Perth Hospital, Perth, Australia
Stanford Blood Center, Group 1, CA, USA
Stanford Blood Center, Group 2, CA, USA
Stanford Blood Center, Group 3, CA, USA
Transplantation and Immunology, Tuebingen, Germany
Transplantation Immunology, Ulm, Germany
UCLA, CA, USA
UNC-Chapel Hill, NC, USA
Uppsala University, Uppsala, Sweden
University of Vienna, Vienna, Austria

 

Table 2 shows the sequencing platforms utilized by different laboratories to perform NGS based HLA typing.

Table 2. NGS Platforms used by participating laboratories
Platform Number of laboratories
GS Roche Junior 1
Illumina MiSeq 8
Ion Torrent Personal Genome Machine (PGM) 4
Pacific Biosciences 2

 

Results

Genotyping

Genotyping results are shown in Tables 3 and 4. All 15 laboratories performed full-length gene sequencing of HLA-A, -B and -C alleles. For HLA-A, 32 different alleles were typed; two of these alleles were reported as novel intronic variants. HLA-B typing identified 54 alleles, including one allele with a novel exon variant and eight with novel intronic variants. HLA-C typing identified 31 alleles, of which two included novel exon variants. Only four laboratories typed DPA1, and collectively identified 11 different DPA1 alleles. DPB1 was genotyped by 10 laboratories and 19 unique alleles were sequenced. Thirteen laboratories typed DQB1, and six laboratories genotyped DQA1, identifying 19 and 23 unique alleles respectively. For DRB1, a total of 13 laboratories used different primer pairs that generated various ranges of gene coverage (full gene, exons 2 and 3, or exons 2, 3, 4 only), and identified a total of 39 unique alleles. Five laboratories typed DRB3 (number of alleles identified, n = 4), DRB4 (n = 4), and DRB5 (n = 3).

 

Table 3. Total number of heterozygous and homozygous alleles in the QC panel
HLA Locus Heterozygous Homozygous Total
A 72 28 100
B 78 22 100
C 72 28 100
DPA1 42 58 100
DPB1 54 46 100
DQA1 74 26 100
DQB1 68 32 100
DRB1 80 20 100
DRB3 10 48 58
DRB4 10 36 46
DRB5 0 12 12

 

Table 4. The number of unique and novel alleles identified by participating laboratories
Locus Alleles Novel Exon variants Novel Intron variants
A 32 0 2
B 54 1 8
C 31 2 0
DPA1 11 0 0
DPB1 19 0 0
DQA1 23 0 0
DQB1 19 0 0
DRB1 39 0 0
DRB3 4 0 0
DRB4 4 0 0
DRB5 3 0 0

 

Cloning

Cloning experiments to generate full-length unambiguous gene sequences were conducted at the Stanford Blood Center. Class I loci in all 50 QC samples were cloned and sequenced at full genomic-length using Illumina NGS. Cloning and sequencing extended or confirmed allele sequence diversity in all HLA loci. Novel alleles and alleles with extended genomic sequences were identified and generated for 12, 14, and 2 alleles in HLA-A, -B, and -C respectively. DPA1 and DPB1 novel/extended alleles were identified for 7 and 15 alleles respectively. Twenty DQA1 alleles and 9 DQB1 alleles were successfully cloned and full- genomic length sequenced. For DRB1, 100 alleles were cloned and sequenced from exons 1 to 2 and exons 2 through 6. Forty-one DRB1 alleles were identified as novel/extended. For DRB3, DRB4 and DRB5, 14, 6, and 6 alleles were found to be novel.

 

Concordance

Due to incomplete and low-resolution reference genotypes for the QC panel, concordance rates were calculated by comparing NGS genotypes from each individual laboratory with consensus genotypes across all laboratories (including cloned data). Testing laboratories were coded A through O (Table 5). Concordance was determined at 2-field resolution. Consensus assignments were high for most laboratories and for most HLA loci. Only one laboratory had a low concordance rate for one locus (DQA1).

 

  Table 5. Concordance rates of participants NGS genotype compared to consensus genotypes
Group HLA-A HLA-B HLA-C HLA-DPA HLA-DPB HLA-DQA HLA-DQB HLA-DRB1 HLA-DRB3 HLA-DRB4 HLA-DRB5
A 100 100 100 98 100 100 100 100 100 NC 100
B 100 100 100 99.0 100 98.0 99.0 98.0 100 NC 100
C 98.0 97.0 100 99.0 100 99.0 100 97.0 100 NC 83.3
D 99.0 100 100 100 100 98.0 100 98.0 100 NC 100
E 98.0 98.0 94.0 NT 100 28.0 100 100 100 NC 100
F 93.2 98.9 100 NT 98.9 98.9 97.8 93.3 NT NT NT
G 100 100 100 NT 100 NT 100 100 NT NT NT
H 100 100 100 NT NT NT 100 100 NT NT NT
I 100 100 100 NT 99.0 NT 98.0 98.0 NT NT NT
J 96.6 93.0 95.5 NT 95.9 NT 94.4 90.9 NT NT NT
K 100 100 100 NT NT NT 100 92.7 NT NT NT
L 100 94.0 100 NT NT NT 95.0 94.0 NT NT NT
M 97.6 96.3 95.0 NT 100 NT 96.8 96.9 NT NT NT
N 100 100 100 NT NT NT NT NT NT NT NT
O 98.0 96.0 98.0 NT NT NT NT NT NT NT NT

 

NT = not tested

NC = not calculated unable to generate a consensus genotype.

 

The results of this study allow us to conclude that HLA typing by various methods is feasible and accurate results can be obtained by various library preparation protocols, platforms and software. We have applied the significant information gained in this effort to design the 17th IHIWS database, as well as to develop strategies for collection of HLA genotype data and the storage of primary data to perform re-analyses as a workshop activity.

We thank the Fred Hutchinson Cancer Research center for supplying the QC samples and all laboratories that participated in the study.

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T Cell Receptor (TCR)-HLA Interaction http://ihiws.org/t-cell-receptor-tcr-hla-interaction/ Wed, 08 Jun 2016 19:17:16 +0000 http://ihiws.org/?p=1137 The T cell receptor is the natural receptor of the HLA-peptide complex and interacts directly with MHC molecules, notably their CDR regions.  The goal of this project will be to combine analysis of TCR and HLA in the context of disease, vaccination/immune alterations and populations.  We would expect samples to be CD4 or CD8 T cells and to have full HLA class I and class II typing by NGS.

Required NGS HLA loci: HLA-A, B, C, DRB1, DRB3/4/5, DQB, HLA-DQA, DPA, DPB
Optional NGS HLA Loci: MICA, MICB

Subprojects for this component will include:
  • Disease study:  This will involve... Read More]]> The T cell receptor is the natural receptor of the HLA-peptide complex and interacts directly with MHC molecules, notably their CDR regions.  The goal of this project will be to combine analysis of TCR and HLA in the context of disease, vaccination/immune alterations and populations.  We would expect samples to be CD4 or CD8 T cells and to have full HLA class I and class II typing by NGS.

    Required NGS HLA loci: HLA-A, B, C, DRB1, DRB3/4/5, DQB, HLA-DQA, DPA, DPB
    Optional NGS HLA Loci: MICA, MICB

    Subprojects for this component will include:

    • Disease study:  This will involve a meta-analysis of all autoimmune disorders for the report of the workshop and individual disease analysis that will be lead by specific investigators.  These may include case/control and longitudinal studies.
    • TCR usage/HLA study:  This will involve studying changes in usage and CDR1/CDR2 regions as a function of HLA types.  The analysis will be performed in control samples, and could possibly be applied to specific diseases.
    • Technical and nomenclature study:  This will involve comparisons of various commercially available techniques using the same samples and normalization of nomenclature.  We plan to have five samples that will be part of quality control to be sequenced by all labs doing NGS.  Finally, pipelines for TCR analysis will be made available to all other components.
    • Transplantation study:  This will involve the study of the TCR repertoire in relation to HLA in transplantation.
      GWAS-TCR study:  We will ask GWAS data or extra 1ug DNA to be contributed when available to study genome wide and TCR cis QTL effects on the TCR repertoire. This will allow HLA imputation studies.

    Analysis and publications:

    Raw sequences for TCR and HLA NGS will be hosted by the workshop so that multiple analytical techniques can be performed.  Data analysis will be conducted separately for each study.  It will be possible to publish separately these sub-studies providing the component heads agree and verify there is no conflict.

    Register to participate by accessing the IHIWS database at https://workshop.ihiws.org or by clicking the “Register to Participate” button at the top of this page.

    Project Leaders:

    Sami Djoulah, PhD. (sami.Djoulah@wiratech.com)
    Emmanuel Mignot MD, PhD (mignot@stanford.edu)

     

    Project Requirements:

    Download Requirements

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    Extension of HLA allele sequences by full-length HLA allele-specific hemizygous Sanger sequencing (SSBT) http://ihiws.org/extension-of-hla-allele-sequences-by-full-length-hla-allele-specific-hemizygous-sanger-sequencing-ssbt/ http://ihiws.org/extension-of-hla-allele-sequences-by-full-length-hla-allele-specific-hemizygous-sanger-sequencing-ssbt/#respond Wed, 29 Jul 2015 17:55:16 +0000 http://ihiws.org/?p=876 The Human Leucocyte Antigen (HLA) is one of the most polymorphic gene systems present in the human genome and due to this high polymorphism, the golden standard for typing at the allele level has been and still is sequence based typing. Since sequencing strategies have mainly focused on identification of the peptide binding groove, therefore the majority of HLA alleles lack full length sequence information.

    The goal of this project is to extend the sequences of as many incompletely covered HLA alleles as possible by full length unambiguous Sanger Sequencing. Although NGS approaches are currently implemented in several laboratories, many... Read More]]> The Human Leucocyte Antigen (HLA) is one of the most polymorphic gene systems present in the human genome and due to this high polymorphism, the golden standard for typing at the allele level has been and still is sequence based typing. Since sequencing strategies have mainly focused on identification of the peptide binding groove, therefore the majority of HLA alleles lack full length sequence information.

    The goal of this project is to extend the sequences of as many incompletely covered HLA alleles as possible by full length unambiguous Sanger Sequencing. Although NGS approaches are currently implemented in several laboratories, many laboratories combine NGS with Sanger sequencing or use Sanger sequencing only as high resolution typing approach. For those labs that are not able to perform NGS, this project offers the possibility to actively participate in the workshop with Sanger Sequencing. Within this project full length Sanger sequencing of alleles with partially known allele sequences will be performed. The Maastricht SSBT approach enables full-length sequencing and separates the alleles based on available low-resolution typing data. The previous problem with Sanger sequencing were three kinds of ambiguities: (1) genotype ambiguity due to cis-trans polymorphism, (2) allele ambiguity due to polymorphism outside the peptide-binding groove and (3) ambiguities due to incomplete sequences. With the Maastricht approach of Sanger sequencing ambiguities (1) and (2) are resolved by hemizygous and full length sequencing, respectively, whereas the ambiguity (3) will be taken care off by the workshop to complete the sequences of as many HLA alleles as possible.

    The Maastricht HLA SSBT approach is previously described (Voorter et al 2014). Based on the low resolution data the SSBT groups for group-specific full length amplification and sequencing are selected, resulting in hemizygous unambiguous allele sequences so that cis-trans phasing is not an issue. Furthermore, since this approach reveals full-length gene sequences this methodology can be used to identify and confirm new allele sequence polymorphism of alleles with unknown intron and exons. Participants will receive SSBT reagents and a detailed protocol, which after QA can be used to identify the full-length sequence of those alleles of which the sequence is not yet completely covered.   All cells encountered in your laboratory from which it is known that the sequence info is incomplete (IMGT/HLA) are candidates to study. A list of these alleles can be found at the IMGT/HLA database. If you have such candidates and you are not able to perform the full length sequencing yourself, you can still participate by sending these candidates to the project leaders for inclusion in the workshop.

    Reference:

    Voorter CE, Palusci F ,Tilanus MG. Sequence-based typing of HLA: an improved group specific full-length gene sequencing approach 2014: 101-14. In: Beksac M, ed. Methods Mol. Biol. Humana Press, New York

    Goal: To extend the sequences of as many incompletely covered HLA alleles as possible by full length unambiguous Sanger Sequencing.

    Participation: Investigators can participate in this project by:

    • HLA SSBT typing of locally collected specimens. In 2015 the Maastricht SSBT kit for research use only (RUO) will be available to the participants. Each participant lab will test a set of five blinded DNA samples as quality control to evaluate the performance. These samples will be provided by the organization and will have to be full length sequenced. Both quality control samples and SSBT kit reagents will be provided by the IHIWS organizing committee and Maastricht group for the IHIWS SSBT project respectively, but participants will be charged for shipment fee. The laboratories performing testing are submitting raw sequencing data and genotype results electronically.
    • Submission of DNA specimens including one or more incompletely covered HLA allele(s). For submission it is necessary that the specimen has previously been HLA typed. These typing data must be provided to the organization. The Maastricht Laboratory will resolve full length sequences of as many of these specimen as possible.

    All full-length sequences will be submitted to the EMBL and IMGT/HLA database. The participating laboratory is the reference submitter for the nomenclature report. Details on submission will follow. In case a sample has only been full length sequence typed for a single locus by the participant, the participant needs to provide additional DNA to the IHIWS workshop to enable NGS for typing all HLA loci full length.

    Project leaders: Marcel GJ Tilanus, Christien EM Voorter, Mathijs Groeneweg

    Contact information:

    Marcel Tilanus: m.tilanus@mumc.nl
    Christien Voorter: c.voorter@mumc.nl
    Mathijs Groeneweg: m.groeneweg@mumc.nl

    Department of Transplantation Immunology,
    Tissue Typing Laboratory,
    Maastricht University Medical Center
    P.O. Box 5800
    6202 AZ Maastricht
    The Netherlands

    Phone: +31 43 3874680
    Fax: +31 43 3874678

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    Pharmacogenetics and HLA http://ihiws.org/pharmacogenetics-and-hla/ Fri, 18 Nov 2016 01:19:53 +0000 http://ihiws.org/?p=1227 Serious adverse reactions to some drugs are associated with certain HLA alleles in some ethnic groups, but have not been investigated in other populations. The project will include a retrospective study of HLA alleles in patients of different ethnic groups who had adverse reactions to carbamazepine. Additional associations may be established for other drugs with increasing awareness of possible immunogenetic predisposition.

    Project Leaders:

    Clara Gorodezky Ph.D. (clarag@unam.mx)
    Maria Bettinotti Ph.D. (mbettinotti@jhmi.edu)

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    Serious adverse reactions to some drugs are associated with certain HLA alleles in some ethnic groups, but have not been investigated in other populations. The project will include a retrospective study of HLA alleles in patients of different ethnic groups who had adverse reactions to carbamazepine. Additional associations may be established for other drugs with increasing awareness of possible immunogenetic predisposition.

    Project Leaders:

    Clara Gorodezky Ph.D. (clarag@unam.mx)
    Maria Bettinotti Ph.D. (mbettinotti@jhmi.edu)

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    Immunogenetics of Aging http://ihiws.org/immunogenetics-of-aging/ Fri, 18 Nov 2016 01:14:26 +0000 http://ihiws.org/?p=1218 The aging process is very complex and longevity is a multifactorial trait, which is determined by genetic and environmental factors.  The aim of the component “Immunogenetics of Aging” is to identify new biomarkers for successful aging and an increased capacity to reach the extreme limits of lifespan by analysis of immune response genes.

    Project Leaders

    Elissaveta Naumova, Ph.D. (immunology@abv.bg)
    Milena Ivanova, Ph.D.  (mivanova@intech.bg)

    Download Project Requirements

    Immunogenetics of Aging (PDF)

     

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    The aging process is very complex and longevity is a multifactorial trait, which is determined by genetic and environmental factors.  The aim of the component “Immunogenetics of Aging” is to identify new biomarkers for successful aging and an increased capacity to reach the extreme limits of lifespan by analysis of immune response genes.

    Project Leaders

    Elissaveta Naumova, Ph.D. (immunology@abv.bg)
    Milena Ivanova, Ph.D.  (mivanova@intech.bg)

    Download Project Requirements

    Immunogenetics of Aging (PDF)

     

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    Disease Association http://ihiws.org/disease-association/ http://ihiws.org/disease-association/#respond Tue, 05 Jan 2016 04:32:18 +0000 http://ihiws.org/?p=976 The application of NGS-HLA typing to screen susceptibility to certain diseases could be useful to further refine and pinpoint the causative HLA polymorphism. One of the goals of the 17th IHIWS disease component is to collect NGS HLA-disease association data conducted worldwide on autoimmune diseases, infectious diseases, cancers, and identify additional genetic determinants predisposing to disease. Investigators may submit both family and population based NGS HLA data or samples only.

    ]]>
    The application of NGS-HLA typing to screen susceptibility to certain diseases could be useful to further refine and pinpoint the causative HLA polymorphism. One of the goals of the 17th IHIWS disease component is to collect NGS HLA-disease association data conducted worldwide on autoimmune diseases, infectious diseases, cancers, and identify additional genetic determinants predisposing to disease. Investigators may submit both family and population based NGS HLA data or samples only.

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    Study of Unrelated Subjects by NGS HLA http://ihiws.org/study-of-unrelated-subjects-by-ngs-hla/ http://ihiws.org/study-of-unrelated-subjects-by-ngs-hla/#respond Tue, 05 Jan 2016 04:32:37 +0000 http://ihiws.org/?p=978 Anthropological studies by NGS of full-length HLA genes to confirm and further characterize alleles and haplotypes identified in unrelated subjects from populations of interest. Subjects should be previously HLA typed at any level (serology, DNA). Investigators may submit samples only or samples and NGS data.

    Project leader: Harriet Noreen (harrietnoreen@hotmail.com)
    Project Leader: Steven J Mack (sjmack@chori.org)

    Requirements for participating in this project:

    Download

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    Anthropological studies by NGS of full-length HLA genes to confirm and further characterize alleles and haplotypes identified in unrelated subjects from populations of interest. Subjects should be previously HLA typed at any level (serology, DNA). Investigators may submit samples only or samples and NGS data.

    Project leader: Harriet Noreen (harrietnoreen@hotmail.com)
    Project Leader: Steven J Mack (sjmack@chori.org)

    Requirements for participating in this project:

    Download

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    Study of Haplotypes in Families by NGS HLA http://ihiws.org/study-of-haplotypes-in-families-by-ngs-hla/ http://ihiws.org/study-of-haplotypes-in-families-by-ngs-hla/#respond Tue, 05 Jan 2016 04:33:22 +0000 http://ihiws.org/?p=981 Anthropological study of families by NGS of full-length HLA genes to determine haplotype segregation in multiple populations. Samples from family quartets consisting of two parents and at least two non-HLA identical children or family trios consisting of one parent and at least two non-HLA identical children are required. The families should be previously HLA typed at any level (serology, DNA). Investigators may submit samples only or samples and NGS data.

    Project Leader: Medhat Askar (Medhat.Askar@BSWHealth.org)
    Kazutoyo Osoegawa, PhD (kazutoyo@stanford.edu)

     

    Requirements for participating in this project:

    Download

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    Anthropological study of families by NGS of full-length HLA genes to determine haplotype segregation in multiple populations. Samples from family quartets consisting of two parents and at least two non-HLA identical children or family trios consisting of one parent and at least two non-HLA identical children are required. The families should be previously HLA typed at any level (serology, DNA). Investigators may submit samples only or samples and NGS data.

    Project Leader: Medhat Askar (Medhat.Askar@BSWHealth.org)
    Kazutoyo Osoegawa, PhD (kazutoyo@stanford.edu)

     

    Requirements for participating in this project:

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    Characteristics and Distribution of Unusual Haplotypes by NGS HLA http://ihiws.org/characteristics-and-distribution-of-unusual-haplotypes-by-ngs-hla/ http://ihiws.org/characteristics-and-distribution-of-unusual-haplotypes-by-ngs-hla/#respond Tue, 05 Jan 2016 04:33:54 +0000 http://ihiws.org/?p=983 NGS of full-length HLA genes typing to confirm and further characterize alleles identified as unusual haplotypes and compare the frequency of these to haplotypes identified from the family studies project in multiple populations. The subjects and families should be previously HLA typed at any level (serology, DNA).

    Project leader: Harriet Noreen (harrietnoreen@hotmail.com)

    Requirements for participating in this project:

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    NGS of full-length HLA genes typing to confirm and further characterize alleles identified as unusual haplotypes and compare the frequency of these to haplotypes identified from the family studies project in multiple populations. The subjects and families should be previously HLA typed at any level (serology, DNA).

    Project leader: Harriet Noreen (harrietnoreen@hotmail.com)

    Requirements for participating in this project:

    Download

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