A5066597492- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Genomic variations and chromosomal abnormalities
- Eosinophilic Disorders and Syndromes
- COVID-19 Clinical Research Studies
- Reproductive System and Pregnancy
- Genomics and Phylogenetic Studies
- SARS-CoV-2 and COVID-19 Research
- Autoimmune Neurological Disorders and Treatments
- Chromosomal and Genetic Variations
- Hematopoietic Stem Cell Transplantation
University of Colorado Denver
2023-2025
University of Colorado Anschutz Medical Campus
2022-2024
Diverse sets of complete human genomes are required to construct a pangenome reference and understand the extent complex structural variation. Here, we sequence 65 diverse build 130 haplotype-resolved assemblies (130 Mbp median continuity), closing 92% all previous assembly gaps reaching telomere-to-telomere (T2T) status for 39% chromosomes. We highlight continuity loci, including major histocompatibility (MHC), SMN1/SMN2, NBPF8, AMY1/AMY2, fully resolve 1,852 variants (SVs). In addition,...
Interactions of killer cell immunoglobin-like receptors (KIR) with human leukocyte antigens (HLA) class I regulate effector functions key cytotoxic cells innate and adaptive immunity. The extreme diversity this interaction is genetically determined, having evolved in the ever-changing environment pathogen exposure. Diversity KIR HLA genes further facilitated by their independent segregation on separate chromosomes. That fetal implantation relies many same types immune as infection control...
Accurate and comprehensive immunogenetic reference panels are key to the successful implementation of population‐scale immunogenomics. The 5Mbp Major Histocompatibility Complex ( MHC ) is most polymorphic region human genome associated with multiple immune‐mediated diseases, transplant matching therapy responses. Analysis genetic variation severely complicated by complex patterns sequence variation, linkage disequilibrium a lack fully resolved haplotypes, increasing risk spurious findings on...
ABSTRACT Killer cell immunoglobulin‐like receptors (KIRs) regulate natural killer (NK) responses by activating or inhibiting their functions. Genotyping KIR genes from short‐read second‐generation sequencing data remains challenging as cross‐alignments among and alignment failure arise gene similarities extreme polymorphism. Several bioinformatics pipelines programs, including PING T1K, have been developed to analyse diversity. We found discordant results tools in a systematic comparison...
The Major Histocompatibility Complex (MHC) of human chromosome 6 contains multiple genes critical for immunity. exceptional polymorphism this genomic region that establishes and maintains immune diversity can be technically challenging to characterise analyse. In study, we present a family where the mother one her children have no HLA-B allele in common, implying absence from maternal haplotype. Homozygosity child was confirmed using three independent PCR-based methods high throughput DNA...
Extreme polymorphism of HLA and killer‐cell immunoglobulin‐like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets class I act as ligands for inhibitory activating KIR, allowing natural killer (NK) cells detect kill infected cells. We investigated the impact KIR on severity COVID‐19. High resolution II genotypes were determined from 403 non‐hospitalized 1575 hospitalized SARS‐CoV‐2 patients Italy collected in 2020. observed...
Abstract The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit usefulness reference-based alignment methods for sequence assembly. We incorporate a short read de novo assembly algorithm into workflow novel application to MHC. MHConstructor is containerized pipeline designed high-throughput, haplotype-informed, reproducible both whole genome sequencing and target-capture data in large, population cohorts. To-date, no other...
Genetic predisposition to autoimmune encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDAR) is poorly understood. Given the diversity of associated environmental factors (tumors, infections), we hypothesized that human leukocyte antigen (
Abstract Accurate and comprehensive immunogenetic reference panels are key to the successful implementation of population-scale immunogenomics. The 5Mbp Major Histocompatibility Complex (MHC) is most polymorphic region human genome associated with multiple immune-mediated diseases, transplant matching therapy responses. Analysis MHC genetic variation severely complicated by complex patterns sequence variation, linkage disequilibrium a lack fully resolved haplotypes, increasing risk spurious...
A fundamental endeavor of the International Histocompatibility and Immunogenetics Workshop (IHIW) was assembling a collection DNA samples homozygous through MHC genomic region. This proved invaluable for assay development in histocompatibility immunogenetics field, generating human reference genome, furthered our understanding diversity. Defined by their HLA ‐ , B C DRB1 alleles, combined frequency haplotypes from these individuals is ∼20% Europe. Thus, significant proportion haplotypes,...
The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit usefulness reference-based alignment methods for sequence assembly. We incorporate a short-read, de novo assembly algorithm into workflow novel application to MHC. MHConstructor is containerized pipeline designed high-throughput, haplotype-informed, reproducible both whole genome sequencing and target capture short-read data in large, population cohorts. To-date, no other...