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

Area of Science:

• Immunogenetics
• Medical Genetics
• Bioinformatics

Background:

• Human leukocyte antigen (HLA) genotype knowledge is vital for medical genetics and transplantation.
• High polymorphism in HLA genes leads to ambiguity in current genotyping methods.
• Existing National Marrow Donor Program (NMDP) allele codes are insufficient for current high-resolution HLA typing.

Purpose of the Study:

• To introduce a novel text string format, the Genotype List (GL) String, for unambiguous HLA genotyping.
• To provide a standardized method for representing complex HLA allele and genotype information.
• To replace outdated NMDP codes with a more robust and informative reporting system.

Main Methods:

• Developed the Genotype List (GL) String format, extending a standard for killer-cell immunoglobulin-like receptor (KIR) genotype data.
• Utilized a hierarchical set of operators to define relationships between alleles, genotypes, and phased/unphased data.
• Designed the format for compatibility with any genetic data using standard variant nomenclature.

Main Results:

• The GL String format accurately represents complex HLA genotyping results without increased ambiguity.
• It accommodates various levels of genetic information, including allele lists, phased alleles, and multilocus genotypes.
• The format is adaptable for diverse genetic data beyond HLA typing.

Conclusions:

• The GL String format provides a superior alternative to NMDP codes for reporting HLA genotypes.
• This standardized approach will enhance precision in HLA typing for clinical and research applications.
• Implementation of GL Strings with appropriate tools will improve data exchange and reduce ambiguity in genetic reporting.