Steven G E Marsh

University College London | UCL · UCL Cancer Institute

The reported influence of donor Killer-cell Immunoglobulin-like Receptor (KIR) genes on the outcomes of haematopoietic cell transplantation (HCT) are contradictory, in part due to diversity of disease, donor sources, era and conditioning regimens within and between different studies. Here, we describe the results of a retrospective clinical analysi...

A novel variant of HLA‐C*03:04:01:47 was identified using Pacific Biosciences SMRT sequencing platform. This article is protected by copyright. All rights reserved.

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine population frequencies and matchi...

We have developed a genotyping assay that produces fully‐phased, unambiguous HLA‐E genotyping using Pacific Biosciences’ Single Molecule Real‐Time (SMRT) DNA sequencing. In total 212 cell lines were genotyped, including the panel of 107 established at the 10th International Histocompatibility Workshop (IHW). Our results matched the previously known...

Natural killer (NK) cell recognition and killing of target cells are enhanced when inhibitory killer immunoglobulin-like receptors (KIR) are unable to engage their cognate HLA class I ligands. The genes of the KIR locus are organized into either KIR B haplotypes, containing 1 or more activating KIR genes or KIR A haplotypes, which lack those genes....

The major histocompatibility complex (MHC) is central to the innate and adaptive immune responses of jawed vertebrates. Characteristic of the MHC are high gene density, gene copy number variation, and allelic polymorphism. Because apes and monkeys are the closest living relatives of humans, the MHCs of these non-human primates (NHP) are studied in...

The Immuno Polymorphism Database (IPD), https://www.ebi.ac.uk/ipd/, is a set of specialist databases that enable the study of polymorphic genes which function as part of the vertebrate immune system. The major focus is on the hyperpolymorphic major histocompatibility complex (MHC) genes and the killer-cell immunoglobulin-like receptor (KIR) genes,...

The original version of this article contained a spelling error in the Acknowledgments regarding the name of the funding organisation supporting GM and JAH. UKRI-BBSCR should have been UKRI-BBSRC, as is now indicated correctly below.

The Killer-cell Immunoglobulin-like Receptors (KIR) are encoded by a diverse group of genes, which are characterized by allelic polymorphism, gene duplications, and recombinations, which may generate recombinant entities. The number of reported macaque KIR sequences is steadily increasing, and these data illustrate a gene system that may match or e...

The assignment of an HLA allele name to a sequence requires a comparison between the generated target sequence and a reference sequence on the IPD‐IMGT/HLA Database. Absence of a full‐length reference sequence can result in the inability of HLA typing software to accurately compare and assign the sequence. We sequenced the most frequently seen HLA...

The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the...

Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which dif...

The novel allele, HLA‐C*07:01:01:30 differs by one nucleotide substitution with HLA‐C*07:01:01:01 at gDNA 627. This article is protected by copyright. All rights reserved.

HLA‐DRB1*01:01:01:02 is the first reported intronic variant of DRB1*01:01:01, differing by a single nucleotide substitution. This article is protected by copyright. All rights reserved.

Pacific Biosciences' SMRT sequencing method was used to extend the sequence of HLA‐A*02:13. This article is protected by copyright. All rights reserved.

Novel allele HLA‐B*56:67 potentially formed by recombination between B*56:01:01:03 and B*40:01:01. This article is protected by copyright. All rights reserved.

A total of 102 Costa Ricans of African-Caribbean descent were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified...

A total of 155 Nicaraguan Mestizos from across the country were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identifi...

A total of 110 Costa Rican Mestizos from the province of Guanacaste were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype...

A total of 125 Costa Ricans of Amerindian descent were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*...

A total of 221 Costa Rican Mestizos from the Central Valley were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, and -DQB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype...

HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplanta-tion (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not...

Objective: The aim of this study was to assess the HLA haplotype frequencies and genetic profiles of the Kuwaiti population. Materials and methods: Whole venous blood was obtained from 595 healthy, unrelated Kuwaiti volunteers. The study population was genotyped for HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) loci...

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classic...

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups...

The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, th...

Allogeneic hematopoietic cell transplantation (alloHCT) remains the sole curative therapy for patients with chronic lymphocytic leukemia (CLL), leading to 40% to 45% long-term survival. The impact of donor killer immunoglobulin-like receptor (KIR) genotype on outcomes of unrelated donor (URD) alloHCT for CLL is unknown. We examined 573 adult URD CL...

The IPD-MHC Database is the official repository for non-human MHC sequences, overseen and supported by the Comparative MHC Nomenclature Committee, providing access to curated MHC data and associated analysis tools. To address the increasing amount and complexity of data being submitted, an entirely upgraded version of the IPD-MHC Database was recen...

Significant progress has been made over the last decade in defining major histocompatibility complex (MHC) diversity at the nucleotide, allele, haplotype, diplotype, and population levels in many non-human species. Much of this progress has been driven by the increased availability and reduced costs associated with nucleotide sequencing technologie...

Pacific Bioscience's SMRT DNA sequencing was used to identify two novel intronic variants of HLA‐A*32:01:01:01. This article is protected by copyright. All rights reserved.

Pacific Bioscience's SMRT sequencing was used to confirm and extend HLA‐DPB1*64:01N and 701:01. This article is protected by copyright. All rights reserved.

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populat...

The increasing number of Killer Immunoglobulin-like Receptor (KIR) sequences available for non-human primate species and cattle has prompted development of a centralized database, guidelines for a standardized nomenclature, and minimum requirements for database submission. The guidelines and nomenclature are based on those used for human KIR and in...

We previously reported that AML transplants using KIR B haplotype Better or Best (≥2 B activating gene loci ± Cen B/B) unrelated donors (URD) yield less relapse and better survival. In this prospective trial we evaluated 535 AML searches from 14 participating centers with centralized donor KIR genotyping for donor selection. This represented 3-48%...

The novel HLA alleles B*40:331, B*40:343, B*42:24, DRB1*01:74, DQB1*03:243, DQB1*03:02:20 were identified in Brazilian individuals. This article is protected by copyright. All rights reserved.

Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will be extremely expensive and labor-intensive to make iPSCs to realize personalized medicine. An alternative approach is to make use of human leukocyte antigen (HLA) haplotype homozygous donors to prov...

The IMGT/HLA Database has provided a repository for information regarding polymorphism in the genes of the immune system since 1998. In 2003, it was absorbed into the Immuno Polymorphism Database (IPD). The IPD project has enabled us to create and maintain a platform for curating and publishing locus-specific databases which are either involved dir...

The HLA system shows a combination of extensive polymorphism and conserved haplotypes. Allelic and haplotypic frequencies of HLA genes vary greatly across human populations, and many alleles and haplotypes are region-specific. Populations in Latin America have a complex history of migration resulting in a broad variety of admixture proportions invo...

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries...

The novel KIR2DL1*037 allele discovered and characterised by Single Molecule Real‐Time (SMRT) DNA Sequencing

Full length KIR2DL1 allele sequence extensions characterised by Single Molecule Real‐Time (SMRT) DNA Sequencing