Targeted and complete genomic sequencing of the major histocompatibility complex in haplotypic form of individual heterozygous samples.

Autor:	Hu T; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Mosbruger TL; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Tairis NG; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Dinou A; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Jayaraman P; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Sarmady M; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Brewster K; Sequencing and Genotyping Center, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19713, USA., Li Y; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Hayeck TJ; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Duke JL; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA., Monos DS; Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; monosd@chop.edu.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2024 Oct 29; Vol. 34 (10), pp. 1500-1513. Date of Electronic Publication: 2024 Oct 29.
DOI:	10.1101/gr.278588.123
Abstrakt:	The human major histocompatibility complex (MHC) is a ∼4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%-99.9% with at least 30× depth) and high accuracy (99.89%-99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine. (© 2024 Hu et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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