冰岛基因解码公司Hannes P. Eggertsson等合作在研究中取得进展。他们构建了冰岛泛基因组参考（HPRC-ICE），并发现了与早发性帕金森病相关的新致病突变。2026年8月19日出版的《自然》杂志发表了这项成果。

参考偏差是影响大多数基因组学分析的问题，这些分析将短读段比对到参考基因组上。通过比对到泛基因组中所代表的多个单倍型，可以缓解这一问题。在此，研究人员介绍了两种解决参考偏差的新方法：用于泛基因组构建的Emblask和用于大规模比对到泛基因组的Weaver。Emblask是一种针对父母-子代三人组的混合长读段和短读段单倍型解析双组装流程。利用Emblask，研究人员组装了698个冰岛单倍型，并将其加入人类泛基因组参考联盟（HPRC）泛基因组中，构建了包含5141万个小型变异的冰岛泛基因组参考（HPRC-ICE）。研究人员用Weaver将57630名冰岛人的短读段比对到HPRC-ICE，并检出了9896万个变异，较比对到线性参考增加了6.17%。研究人员在低比对能力区域发现了新变异，包括一个与早发性帕金森病相关的GBA1致病单核苷酸多态性（SNP），以及一个对同型半胱氨酸尿症具有致病性的CBS错义SNP。研究人员通过对429193名英国和爱尔兰参与者的靶向重比对，在英国生物银行（UK Biobank）中复制了GBA1关联。

附：英文原文

Title: An Icelandic pangenome reference

Author: Holley, Guillaume, Eggertsson, Hannes P., Kristmundsdottir, Snaedis, Beyter, Doruk, Skuladottir, Astros Th, Moore, Kristjan H. S., Olason, Pall I., Gylfason, Arnaldur, Magnusson, Olafur T., Oddsson, Asmundur, Stefansson, Hreinn, Helgason, Agnar, Masson, Gisli, Sulem, Patrick, Gudbjartsson, Daniel F., Stefansson, Kari, Halldorsson, Bjarni V.

Issue&Volume: 2026-08-19

Abstract: Reference bias is an issue that affects most genomic studies analysing short reads mapped to a reference genome. It can be mitigated by mapping to multiple haplotypes represented in a pangenome. Here we introduce two new methods to address reference bias: Emblask for pangenome construction and Weaver for mapping to pangenomes at scale. Emblask is a hybrid long- and short-read haplotype-resolved dual assembly pipeline for parent–offspring trio data. Using Emblask, we assembled 698 Icelandic haplotypes and added them to the Human Pangenome Reference Consortium (HPRC) pangenome to construct an Icelandic pangenome reference (HPRC-ICE) including 51.41 million small variants. We mapped the short reads of 57,630 Icelanders to HPRC-ICE with Weaver and called 98.96 million variants, representing a 6.17% increase over mapping to a linear reference. We uncovered new variants in low-mappability regions, including a pathogenic single nucleotide polymorphism (SNP) in GBA1 that associates with early onset Parkinson’s disease and a missense SNP in CBS that is pathogenic for homocystinuria. We replicated the GBA1 association in the UK Biobank with a targeted remapping of 429,193 British and Irish participants.

DOI: 10.1038/s41586-026-10924-7

Source: https://www.nature.com/articles/s41586-026-10924-7