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  1. Article ; Online: Correction to: The immunogenetics of COVID-19.

    Srivastava, Anshika / Hollenbach, Jill A

    Immunogenetics

    2023  Volume 75, Issue 3, Page(s) 321

    Language English
    Publishing date 2023-02-23
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 186560-2
    ISSN 1432-1211 ; 0093-7711
    ISSN (online) 1432-1211
    ISSN 0093-7711
    DOI 10.1007/s00251-023-01300-0
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  2. Article ; Online: Software update: Interpreting killer-cell immunoglobulin-like receptors from whole genome sequence data with PING.

    Marin, Wesley M / Hollenbach, Jill A

    HLA

    2023  Volume 101, Issue 5, Page(s) 441–448

    Abstract: Here, we demonstrate improvements to our bioinformatic pipeline, PING, which provides high-resolution genotyping of killer-cell immunoglobulin-like receptor (KIR) sequencing data, that expand the method to provide KIR interpretation from whole genome ... ...

    Abstract Here, we demonstrate improvements to our bioinformatic pipeline, PING, which provides high-resolution genotyping of killer-cell immunoglobulin-like receptor (KIR) sequencing data, that expand the method to provide KIR interpretation from whole genome sequencing (WGS) data. We evaluated performance using synthetic sequence datasets and real-world data from the 1000 Genomes Project (1KGP). PING demonstrated high exonic genotyping performance on the synthetic sequence dataset meant to approximate real-world data at 95% accuracy (N = 1366). This result was mirrored in the analysis of 1KGP European data (N = 215) with most genes showing near or below 5% frequency of unresolved exonic genotypes, which is an important indicator for genotyping errors in real-world data. An analysis into the distributions of genotyping errors for the synthetic sequence datasets gave insights into how to further improve genotype accuracy. Similarly, an analysis into ambiguous exonic genotype frequencies for the 1KGP European data, which showed high rates of unresolved genotypes, highlighted that an effective phasing method will be an impactful future additional to the PING workflow. Together, these results demonstrate that PING can effectively provide high-resolution KIR genotyping on WGS data.
    MeSH term(s) Humans ; High-Throughput Nucleotide Sequencing/methods ; Alleles ; Genotype ; Software ; Receptors, KIR/genetics ; Immunoglobulins/genetics
    Chemical Substances Receptors, KIR ; Immunoglobulins
    Language English
    Publishing date 2023-01-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.14949
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  3. Article ; Online: The immunogenetics of COVID-19.

    Srivastava, Anshika / Hollenbach, Jill A

    Immunogenetics

    2022  Volume 75, Issue 3, Page(s) 309–320

    Abstract: The worldwide coronavirus disease 2019 pandemic was sparked by the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) that first surfaced in December 2019 (COVID-19). The effects of COVID-19 differ substantially not just between ... ...

    Abstract The worldwide coronavirus disease 2019 pandemic was sparked by the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) that first surfaced in December 2019 (COVID-19). The effects of COVID-19 differ substantially not just between patients individually but also between populations with different ancestries. In humans, the human leukocyte antigen (HLA) system coordinates immune regulation. Since HLA molecules are a major component of antigen-presenting pathway, they play an important role in determining susceptibility to infectious disease. It is likely that differential susceptibility to SARS-CoV-2 infection and/or disease course in COVID-19 in different individuals could be influenced by the variations in the HLA genes which are associated with various immune responses to SARS-CoV-2. A growing number of studies have identified a connection between HLA variation and diverse COVID-19 outcomes. Here, we review research investigating the impact of HLA on individual responses to SARS-CoV-2 infection and/or progression, also discussing the significance of MHC-related immunological patterns and its use in vaccine design.
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Immunogenetics ; Histocompatibility Antigens Class I/genetics
    Chemical Substances Histocompatibility Antigens Class I
    Language English
    Publishing date 2022-12-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 186560-2
    ISSN 1432-1211 ; 0093-7711
    ISSN (online) 1432-1211
    ISSN 0093-7711
    DOI 10.1007/s00251-022-01284-3
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  4. Article ; Online: HLA variation and antigen presentation in COVID-19 and SARS-CoV-2 infection.

    Augusto, Danillo G / Hollenbach, Jill A

    Current opinion in immunology

    2022  Volume 76, Page(s) 102178

    Abstract: The extraordinary variation of the human leukocyte antigen (HLA) molecules is critical for diversifying antigen presentation to T cells. Coupled with the rise of novel strains and rapidly evolving immune evasion by SARS-CoV-2 proteins, HLA-mediated ... ...

    Abstract The extraordinary variation of the human leukocyte antigen (HLA) molecules is critical for diversifying antigen presentation to T cells. Coupled with the rise of novel strains and rapidly evolving immune evasion by SARS-CoV-2 proteins, HLA-mediated immunity in COVID-19 is critically important but far from being fully understood. A growing number of studies have found the association of HLA variants with different COVID-19 outcomes and that HLA genotypes associate with differential immune responses against SARS-CoV-2. Prediction studies have shown that mutations in multiple viral strains, most concentrated in the Spike protein, affect the affinity between these mutant peptides and HLA molecules. Understanding the impact of this variation on T-cell responses is critical for comprehending the immunogenic mechanisms in both natural immunity and vaccine development.
    MeSH term(s) Antigen Presentation ; COVID-19 ; Epitopes, T-Lymphocyte ; HLA Antigens/genetics ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class II ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Epitopes, T-Lymphocyte ; HLA Antigens ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-03-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2022.102178
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  5. Article: High-throughput complement component 4 genomic sequence analysis with C4Investigator.

    Marin, Wesley M / Augusto, Danillo G / Wade, Kristen J / Hollenbach, Jill A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The complement component 4 gene locus, composed of ... ...

    Abstract The complement component 4 gene locus, composed of the
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.18.549551
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  6. Article ; Online: High-throughput complement component 4 genomic sequence analysis with C4Investigator.

    Marin, Wesley M / Augusto, Danillo G / Wade, Kristen J / Hollenbach, Jill A

    HLA

    2023  Volume 103, Issue 1, Page(s) e15273

    Abstract: The complement component 4 gene loci, composed of the C4A and C4B genes and located on chromosome 6, encodes for complement component 4 (C4) proteins, a key intermediate in the classical and lectin pathways of the complement system. The complement system ...

    Abstract The complement component 4 gene loci, composed of the C4A and C4B genes and located on chromosome 6, encodes for complement component 4 (C4) proteins, a key intermediate in the classical and lectin pathways of the complement system. The complement system is an important modulator of immune system activity and is also involved in the clearance of immune complexes and cellular debris. C4A and C4B gene loci exhibit copy number variation, with each composite gene varying between 0 and 5 copies per haplotype. C4A and C4B genes also vary in size depending on the presence of the human endogenous retrovirus (HERV) in intron 9, denoted by C4(L) for long-form and C4(S) for short-form, which affects expression and is found in both C4A and C4B. Additionally, human blood group antigens Rodgers and Chido are located on the C4 protein, with the Rodger epitope generally found on C4A protein, and the Chido epitope generally found on C4B protein. C4A and C4B copy number variation has been implicated in numerous autoimmune and pathogenic diseases. Despite the central role of C4 in immune function and regulation, high-throughput genomic sequence analysis of C4A and C4B variants has been impeded by the high degree of sequence similarity and complex genetic variation exhibited by these genes. To investigate C4 variation using genomic sequencing data, we have developed a novel bioinformatic pipeline for comprehensive, high-throughput characterization of human C4A and C4B sequences from short-read sequencing data, named C4Investigator. Using paired-end targeted or whole genome sequence data as input, C4Investigator determines the overall gene copy numbers, as well as C4A, C4B, C4(Rodger), C4(Ch), C4(L), and C4(S). Additionally, C4Ivestigator reports the full overall C4A and C4B aligned sequence, enabling nucleotide level analysis. To demonstrate the utility of this workflow we have analyzed C4A and C4B variation in the 1000 Genomes Project Data set, showing that these genes are highly poly-allelic with many variants that have the potential to impact C4 protein function.
    MeSH term(s) Humans ; DNA Copy Number Variations ; Complement C4b/genetics ; Alleles ; Complement C4/genetics ; Genomics ; Sequence Analysis ; Epitopes
    Chemical Substances Complement C4b (80295-50-7) ; Complement C4 ; Epitopes
    Language English
    Publishing date 2023-10-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15273
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  7. Article: High-resolution DNA methylation screening of the major histocompatibility complex in multiple sclerosis.

    Ma, Qin / Augusto, Danillo G / Montero-Martin, Gonzalo / Caillier, Stacy J / Osoegawa, Kazutoyo / Cree, Bruce A C / Hauser, Stephen L / Didonna, Alessandro / Hollenbach, Jill A / Norman, Paul J / Fernandez-Vina, Marcelo / Oksenberg, Jorge R

    Frontiers in neurology

    2023  Volume 14, Page(s) 1326738

    Abstract: Background: The : Methods: We developed and validated an MHC capture protocol coupled with bisulfite sequencing and conducted a comprehensive analysis of the MHC methylation landscape in blood samples from 147 treatment naïve MS study participants ... ...

    Abstract Background: The
    Methods: We developed and validated an MHC capture protocol coupled with bisulfite sequencing and conducted a comprehensive analysis of the MHC methylation landscape in blood samples from 147 treatment naïve MS study participants and 129 healthy controls.
    Results: We identified 132 differentially methylated region (DMRs) within MHC region associated with disease status. The DMRs overlapped with established MS risk loci. Integration of the MHC methylome with human leukocyte antigen (
    Results: The results describe MS-associated methylation changes in MHC region and highlight the association between HLA genotypes and methylation changes. Results from the mQTL and CIT analyses provide evidence linking MHC region variations, methylation changes, and disease risk for MS.
    Language English
    Publishing date 2023-12-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2023.1326738
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  8. Article ; Online: Measuring Race and Ancestry in the Age of Genetic Testing.

    Johfre, Sasha Shen / Saperstein, Aliya / Hollenbach, Jill A

    Demography

    2021  Volume 58, Issue 3, Page(s) 785–810

    Abstract: Will the rise of genetic ancestry tests (GATs) change how Americans respond to questions about race and ancestry on censuses and surveys? To provide an answer, we draw on a unique study of more than 100,000 U.S. adults that inquired about respondents' ... ...

    Abstract Will the rise of genetic ancestry tests (GATs) change how Americans respond to questions about race and ancestry on censuses and surveys? To provide an answer, we draw on a unique study of more than 100,000 U.S. adults that inquired about respondents' race, ancestry, and genealogical knowledge. We find that people in our sample who have taken a GAT, compared with those who have not, are more likely to self-identify as multiracial and are particularly likely to select three or more races. This difference in multiple-race reporting stems from three factors: (1) people who identify as multiracial are more likely to take GATs; (2) GAT takers are more likely to report multiple regions of ancestral origin; and (3) GAT takers more frequently translate reported ancestral diversity into multiracial self-identification. Our results imply that Americans will select three or more races at higher rates in future demographic data collection, with marked increases in multiple-race reporting among middle-aged adults. We also present experimental evidence that asking questions about ancestry before racial identification moderates some of these GAT-linked reporting differences. Demographers should consider how the meaning of U.S. race data may be changing as more Americans are exposed to information from GATs.
    MeSH term(s) Adult ; Censuses ; Genetic Testing ; Humans ; Middle Aged ; Racial Groups/genetics ; Surveys and Questionnaires ; United States ; Whites/genetics
    Language English
    Publishing date 2021-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 280612-5
    ISSN 1533-7790 ; 0070-3370
    ISSN (online) 1533-7790
    ISSN 0070-3370
    DOI 10.1215/00703370-9142013
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  9. Article ; Online: Exceptional diversity of KIR and HLA class I in Egypt.

    Montero-Martin, Gonzalo / Kichula, Katherine M / Misra, Maneesh K / de Brito Vargas, Luciana / Marin, Wesley M / Hollenbach, Jill A / Fernández-Viña, Marcelo A / Elfishawi, Sally / Norman, Paul J

    HLA

    2023  Volume 103, Issue 1, Page(s) e15177

    Abstract: Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen ... ...

    Abstract Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under-studied for many geographic regions. Here, we describe the first high-resolution analysis of KIR and HLA class I combinatorial diversity in Northern Africa. Analysis of 125 healthy unrelated individuals from Cairo in Egypt yielded 186 KIR alleles arranged in 146 distinct centromeric and 79 distinct telomeric haplotypes. The most frequent haplotypes observed were KIR-A, encoding two inhibitory receptors specific for HLA-C, two that are specific for HLA-A and -B, and no activating receptors. Together with 141 alleles of HLA class I, 75 of which encode a KIR ligand, we identified a mean of six distinct interacting pairs of inhibitory KIR and HLA allotypes per individual. We additionally characterize 16 KIR alleles newly identified in the study population. Our findings place Egyptians as one of the most highly diverse populations worldwide, with important implications for transplant matching and studies of immune-mediated diseases.
    MeSH term(s) Humans ; Egypt ; Cross-Sectional Studies ; Alleles ; Multimorbidity ; Receptors, KIR/genetics ; Haplotypes ; North African People
    Chemical Substances Receptors, KIR
    Language English
    Publishing date 2023-08-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15177
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  10. Article ; Online: Genotype List String 1.1: Extending the Genotype List String grammar for describing HLA and Killer-cell Immunoglobulin-like Receptor genotypes.

    Mack, Steven J / Schefzyk, Daniel / Millius, Robert P / Maiers, Martin / Hollenbach, Jill A / Pollack, Jane / Heuer, Michael L / Gragert, Loren / Spellman, Stephen R / Guethlein, Lisbeth A / Schneider, Joel / Bochtler, Werner / Eberhard, Hans-Peter / Robinson, James / Marsh, Steven G E / Schmidt, Alexander H / Hofmann, Jan A / Sauter, Jürgen

    HLA

    2023  Volume 102, Issue 2, Page(s) 206–212

    Abstract: The Genotype List (GL) String grammar for reporting HLA and Killer-cell Immunoglobulin-like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings have been used to describe HLA and KIR genotypes for ... ...

    Abstract The Genotype List (GL) String grammar for reporting HLA and Killer-cell Immunoglobulin-like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings have been used to describe HLA and KIR genotypes for more than 40 million subjects, allowing these data to be recorded, stored and transmitted in an easily parsed, text-based format. After a decade of working with HLA and KIR data in GL String format, with advances in HLA and KIR genotyping technologies that have fostered the generation of full-gene sequence data, the need for an extension of the GL String system has become clear. Here, we introduce the new GL String delimiter "?," which addresses the need to describe ambiguity in assigning a gene sequence to gene paralogs. GL Strings that do not include a "?" delimiter continue to be interpreted as originally described. This extension represents version 1.1 of the GL String grammar.
    MeSH term(s) Humans ; Alleles ; Genotype ; Receptors, KIR/genetics ; Immunoglobulins/genetics ; Gene Frequency
    Chemical Substances Receptors, KIR ; Immunoglobulins
    Language English
    Publishing date 2023-06-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15126
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