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

Abstract

Knowledge of an individual’s 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 twenty 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 KIR genotype data that can be applied to any genetic data that employs a standard nomenclature for identifying variants. The GL String format employs 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.

Immunogenetics of type 1 diabetes: A comprehensive review

“…Current efforts in the HLA community are directed toward standardization of data reporting in HLA studies to allow comparisons to be made among studies [29]. In the future, the time may come when whole genome sequencing becomes standard for every individual, negating the need for specific genotyping of any locus, including those encoding HLA.…”

HLA Haplotype Validator for quality assessments of HLA typing

“…First, the software passes the HLA genotypes through the GL Service to check the accuracy of GL String format [30]. Second, the individual HLA alleles are filtered against the CWD 2.0.0 catalogue [28].…”

“…The file format includes sample name and HLA genotyping data separated by common delimiters (tab or comma). The HLA genotyping data is represented using Genotype List (GL) String format [30]. The software takes a second, optional argument to specify one of the supported haplotype tables.…”

HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population

“…Alleles obtained were valid in the IMGT/HLA database that allows retrieving the information about one particular allele as mentioned in WHO's Committee of Nomenclature [22][23][24][25][26].…”