Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string

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.

Keywords: Genotype List String; genotype; human leukocyte antigen; killer-cell immunoglobulin-like receptor.

Figure 1

Genotype List (GL) String representation of a multilocus unphased genotype. A GL String representing HLA-A genotype (A*02:69 and A*23:30, or A*02:302 and, either A*23:26 or A*23:39) and HLA-B genotype (B*44:02:13 and B*49:08) for a single individual is shown. GL String delimiters are parsed hierarchically starting from the locus delimiter (^), proceeding to the genotype delimiter (|), then the chromosome delimiter (+), and ending with the allele delimiter (/).