**On Genotyping Polymorphic HLA Genes — Ambiguities and Quality Measures Using NGS**

Szilveszter Juhos, Krisztina Rigó and György Horváth

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61592

#### **Abstract**

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The major histocompatibility complex (MHC) region of the human genome is the most polymorphic sequence part on chromosome 6; this roughly 4 Mbase long stretch contains many genes involved in immune response and disease association. The HLA genes have a crucial role in transplantation; patients receiving organs or bone marrow from matching donors have significantly higher chance for survival. NGS-based HLA typing brings the hope of accurate genomic consensus sequences by relatively cheap and simple laboratory workflow. Using either targeted or whole-genome sequencing data, there are a lot of pos‐ sibilities to get ambiguous results (combinations of several alleles as a result instead of a single pair). These can be sample- or reference-related, or the results of artifacts generated during the targeting and amplifying step. NGS technology itself has additional artifacts leading to ambiguity listed in our paper. The final bioinformatics step will not be able to resolve all the ambiguities; we are also proposing quality control metrics to assess the fi‐ nal ambiguity and typing failure.

**Keywords:** HLA, phasing, ambiguity, quality control, novel allele
