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.

中文翻译：

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对单个杂合子样本的单倍型形式的主要组织相容性复合物进行靶向和完整的基因组测序


人类主要组织相容性复合体 （MHC） 是 6 号染色体上 ∼4 Mb 的基因组片段，在免疫反应中起关键作用。尽管它在各种性状和疾病中都很重要，但其复杂性使得在常规基础上准确表征具有挑战性。我们提出了一种新方法，允许使用长读长测序技术对杂合子样本中的 MHC 区域进行靶向测序和从头单倍型组装。我们的方法使用两个参考样本、两个家庭三重奏和一个非裔美国人样本进行了验证。我们对不同的单倍型实现了出色的覆盖度 （96.6%–99.9%，深度至少为 30×）和高精度 （99.89%–99.99%）。该方法提供了一种可靠且经济高效的方法，无需全基因组测序即可对 MHC 进行测序和全面表征，促进了对这一重要基因组片段的更广泛研究，并在免疫学、遗传学和医学方面具有重要意义。