Next-Generation Sequencing of the HLA locus: Methods and impacts on HLA typing, population genetics and disease association studies

摘要: The human Major Histocompatibility Complex, known as the "Human Leukocyte Antigen (HLA)", could be defined a "super locus" (historically called "supergene") governing adaptive immune system in vertebrates. It also harbors genes involved innate immunity. HLA is most gene-dense, polymorphic and disease-associated region of genome. critical medical relevance given its involvement fate transplanted organs/tissues association with more than 100 diseases. However, despite these important roles, comprehensive sequence analysis 4 megabase locus has been limited due to technological challenges. Thanks recent improvements Next-Generation Sequencing (NGS) technologies however, one now able handle peculiarities MHC notably tight linkage disequilibrium between well their high degree polymorphism (and hence heterozygosity). Increased read lengths, throughput, accuracy, development new bioinformatics tools enable efficiently generate complete accurate full-length haplotypes without phase ambiguities. present report reviews current NGS approaches capture, analyze loci. impact methodologies on various applications including typing, population genetics disease studies are discussed.