Abstract
Knowledge of an individual's human leukocyte antigen (HLA) genotype is essential for modern medical genetics, and is crucial for hematopoietic stem cell and solid-organ transplantation. However, the high levels of polymorphism known for the HLA genes make it difficult to generate an HLA genotype that unambiguously identifies the alleles that are present at a given HLA locus in an individual. For the last 20 years, the histocompatibility and immunogenetics community has recorded this HLA genotyping ambiguity using allele codes developed by the National Marrow Donor Program (NMDP). While these allele codes may have been effective for recording an HLA genotyping result when initially developed, their use today results in increased ambiguity in an HLA genotype, and they are no longer suitable in the era of rapid allele discovery and ultra-high allele polymorphism. Here, we present a text string format capable of fully representing HLA genotyping results. This Genotype List (GL) String format is an extension of a proposed standard for reporting killer-cell immunoglobulin-like receptor (KIR) genotype data that can be applied to any genetic data that use a standard nomenclature for identifying variants. The GL String format uses a hierarchical set of operators to describe the relationships between alleles, lists of possible alleles, phased alleles, genotypes, lists of possible genotypes, and multilocus unphased genotypes, without losing typing information or increasing typing ambiguity. When used in concert with appropriate tools to create, exchange, and parse these strings, we anticipate that GL Strings will replace NMDP allele codes for reporting HLA genotypes.
Highlights
The human leukocyte antigen (HLA) genes on human chromosome 6p21 are the most polymorphic and medically relevant genes in the human genome [1,2,3,4]
The high diversity of HLA proteins is driven by their peptide binding function; each protein can present a small population of chemically similar peptides, which are bound by a peptide binding groove formed by a few dozen amino acid residues [6, 10, 11]
We have developed a string format that can fully describe HLA genotyping results
Summary
The human leukocyte antigen (HLA) genes on human chromosome 6p21 are the most polymorphic and medically relevant genes in the human genome [1,2,3,4]. As a consequence of these serologically uncertain alleles and the patchwork structure of the HLA polymorphism, an increasing number of genotyping results include ambiguities involving the 1st field This leads to a growing numbers of allele codes crossing those generic groups. Because the NMDP allele code system cannot accommodate ambiguities in the 1st field, additional HLA typing is often used to exclude these ambiguities, increasing the cost and time required to report a genotype. If an NMDP allele code corresponding to an ambiguity does not exist, or has not been activated for use at a particular locus, the creation of a new code, or the activation of an existing code at a new locus, must be requested This constitutes a ratelimiting step so far as the efficient recording and transmission of HLA genotype data goes.
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