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Principal Investigator: JILL Allison HOLLENBACH
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $788,776
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY
Located within the human Major Histocompatibility Complex (MHC) chromosome 6p21, the Human Leukocyte
Antigen (HLA) region is the most medically important region of the human genome. Variation in the HLA region
has been associated with over 150 diseases and conditions, including infectious disease, cancers, and major
drug-hypersensitivities. While little is known at this point about the impact of host genetic factors in COVID-19,
the epidemiology to-date reveals wide variation in disease course among confirmed cases of infection that does
not appear to be fully explained by known risk factors. Because of its pivotal role in the immune response
understanding the role of HLA variation promises to provide important insights relevant to understanding the
immunopathogenesis of COVID-19, while informing vaccine development and potential immunotherapies. In
Specific Aim 1, we will exploit an existing data resource, partnering with the National Marrow Donor Program
and DKMS registries to collect data on COVID-19 symptoms, testing and outcomes using a novel, validated
smartphone app in a very large sample (N=300,000-500,000) of volunteer bone marrow donors with pre-existing
HLA genotyping data, allowing an extraordinarily well-powered examination of the role of these genes in disease.
In Specific Aim 2, we will employ a novel, validated method for next-generation sequencing of the extended MHC
(~5Mb), including all classical and non-classical HLA loci, as well as over 150 additional immune system loci, in
large and diverse cohorts of COVID-19 patients (N=2000), as well patient cohorts with longitudinal clinical data
and extensive immunoprofiling (N=300). Finally, in Specific Aim 3 we will contextualize these association studies
through examination of the role of HLA presentation of SARS-CoV-2 antigens. In summary, we will leverage
large and diverse patient cohorts alongside cutting edge technology and molecular biology to reveal the role of
these important immune loci in COVID-19.
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Application><Cell phone App><Cells><Cellular Phone App><Cellular Phone Application><Chromosomes><Class I Antigens><Class I Major Histocompatibility Antigens><Class II Antigens><Class II Major Histocompatibility Antigens><Clinical><Clinical Data><CoV-2><CoV2><Communicable Diseases><Complex Class 1><Coronavirus Infectious Disease 2019><Coupled><Coupling><Custom><DNA Molecular Biology><Data><Data Set><Disease><Disease Outcome><Disorder><Drug Allergy><Drug Hypersensitivity><Elements><Epidemiology><Epitopes><Fostering><Functional RNA><Genes><Genetic><Genomic Segment><Genomics><Genotype><Goals><HL-A Antigens><HLA Antigens><Health><Health system><Histocompatibility Antigens Class I><Histocompatibility Antigens Class II><Histocompatibility Complex><Histocompatibility Complices><Human><Human Genome><Human Leukocyte Antigens><I-A Antigen><Ia Antigens><Ia-Like Antigens><Immune><Immune Cell Activation><Immune Response Antigens><Immune mediated therapy><Immune response><Immune 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Genetics><Proteins><Proteomics><Registries><Research Resources><Resolution><Resources><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antigen><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sample Size><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome 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analysis><malignancy><mobile computing><mobile phone app><mobile platform><mobile technology><nCoV2><neoplasm/cancer><next gen sequencing><next generation sequencing><nextgen sequencing><noncoding><novel><pathogen><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><programs><pulmonary><repository><resolutions><response><scientific citizenship><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome 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