文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

一项关于染色体重排的全国长读测序研究揭示了隐藏的复杂性。

A national long-read sequencing study on chromosomal rearrangements uncovers hidden complexities.

机构信息

Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.

Department of Clinical Genetics and Genomics, Karolinska University Hospital, 171 76 Stockholm, Sweden.

出版信息

Genome Res. 2024 Nov 20;34(11):1774-1784. doi: 10.1101/gr.279510.124.


DOI:10.1101/gr.279510.124
PMID:39472022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11610602/
Abstract

Clinical genetic laboratories often require a comprehensive analysis of chromosomal rearrangements/structural variants (SVs), from large events like translocations and inversions to supernumerary ring/marker chromosomes and small deletions or duplications. Understanding the complexity of these events and their clinical consequences requires pinpointing breakpoint junctions and resolving the derivative chromosome structure. This task often surpasses the capabilities of short-read sequencing technologies. In contrast, long-read sequencing techniques present a compelling alternative for clinical diagnostics. Here, Genomic Medicine Sweden-Rare Diseases has explored the utility of HiFi Revio long-read genome sequencing (lrGS) for digital karyotyping of SVs nationwide. The 16 samples from 13 families were collected from all Swedish healthcare regions. Prior investigations had identified 16 SVs, ranging from simple to complex rearrangements, including inversions, translocations, and copy number variants. We have established a national pipeline and a shared variant database for variant calling and filtering. Using lrGS, 14 of the 16 known SVs are detected. Of these, 13 are mapped at nucleotide resolution, and one complex rearrangement is only visible by read depth. Two Chromosome 21 rearrangements, one mosaic, remain undetected. Average read lengths are 8.3-18.8 kb with coverage exceeding 20× for all samples. De novo assembly results in a limited number of phased contigs per individual (N50 6-86 Mb), enabling direct characterization of the chromosomal rearrangements. In a national pilot study, we demonstrate the utility of HiFi Revio lrGS for analyzing chromosomal rearrangements. Based on our results, we propose a 5-year plan to expand lrGS use for rare disease diagnostics in Sweden.

摘要

临床遗传实验室通常需要对染色体重排/结构变异(SVs)进行全面分析,包括易位、倒位等大事件,以及额外的环状/标记染色体和小的缺失或重复。要了解这些事件的复杂性及其临床后果,需要确定断点连接,并解析衍生染色体结构。这项任务通常超出了短读测序技术的能力范围。相比之下,长读测序技术为临床诊断提供了一个引人注目的替代方案。在这里,瑞典罕见病基因组医学中心(Genomic Medicine Sweden-Rare Diseases)探索了 HiFi Revio 长读长基因组测序(lrGS)在全国范围内用于 SV 数字核型分析的应用。从瑞典所有医疗保健地区收集了来自 13 个家庭的 16 个样本。先前的研究已经确定了 16 个 SV,范围从简单到复杂的重排,包括倒位、易位和拷贝数变异。我们已经建立了一个全国性的管道和一个共享的变异数据库,用于变异调用和过滤。使用 lrGS,可检测到 16 个已知 SV 中的 14 个。其中 13 个在核苷酸分辨率下进行映射,一个复杂的重排只能通过读深度可见。两个 21 号染色体重排,一个是镶嵌型,仍然未被检测到。平均读长为 8.3-18.8kb,所有样本的覆盖率均超过 20×。从头组装的结果是每个个体的相位数目有限(N50 为 6-86Mb),能够直接对染色体重排进行特征描述。在全国性的试点研究中,我们展示了 HiFi Revio lrGS 用于分析染色体重排的实用性。根据我们的结果,我们提出了一个为期 5 年的计划,以扩大 lrGS 在瑞典罕见病诊断中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/167be2edd45e/1774f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/ff8765948cdb/1774f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/d2fea862e53d/1774f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/736a33203e1d/1774f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/cc2e7b90db7f/1774f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/167be2edd45e/1774f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/ff8765948cdb/1774f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/d2fea862e53d/1774f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/736a33203e1d/1774f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/cc2e7b90db7f/1774f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89e8/11610602/167be2edd45e/1774f05.jpg

相似文献

[1]
A national long-read sequencing study on chromosomal rearrangements uncovers hidden complexities.

Genome Res. 2024-11-20

[2]
Long-read sequencing and optical mapping generates near T2T assemblies that resolves a centromeric translocation.

Sci Rep. 2024-4-18

[3]
Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly.

Am J Hum Genet. 2024-12-5

[4]
A pipeline for complete characterization of complex germline rearrangements from long DNA reads.

Genome Med. 2020-7-31

[5]
Long-read genome sequencing and variant reanalysis increase diagnostic yield in neurodevelopmental disorders.

Genome Res. 2024-11-20

[6]
Optical genome mapping enables constitutional chromosomal aberration detection.

Am J Hum Genet. 2021-8-5

[7]
Deciphering the complexity of simple chromosomal insertions by genome sequencing.

Hum Genet. 2021-2

[8]
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

Am J Hum Genet. 2025-2-6

[9]
Cryptic genomic imbalances in de novo and inherited apparently balanced chromosomal rearrangements: array CGH study of 47 unrelated cases.

Eur J Med Genet. 2009

[10]
Complex chromosomal 6q rearrangements revealed by combined long-molecule genomics technologies.

Genomics. 2024-9

引用本文的文献

[1]
Chromoanagenesis and Beyond: Catastrophic Events Shaping the Genome.

Methods Mol Biol. 2025

[2]
Chromothripsis.

Methods Mol Biol. 2025

[3]
The Diagnostic Value of Copy Number Variants in Genetic Cardiomyopathies and Channelopathies.

J Cardiovasc Dev Dis. 2025-7-4

[4]
The clinical application and challenges of preimplantation genetic testing.

Front Genet. 2025-6-2

[5]
Toward clinical long-read genome sequencing for rare diseases.

Nat Genet. 2025-5-7

[6]
The RNA Revolution in the Central Molecular Biology Dogma Evolution.

Int J Mol Sci. 2024-11-26

本文引用的文献

[1]
High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation.

Genome Res. 2024-11-20

[2]
Visualization and analysis of medically relevant tandem repeats in nanopore sequencing of control cohorts with pathSTR.

Genome Res. 2024-11-20

[3]
Utility of long-read sequencing for All of Us.

Nat Commun. 2024-1-29

[4]
Whole-genome long-read sequencing downsampling and its effect on variant-calling precision and recall.

Genome Res. 2023-12-27

[5]
Characterization and visualization of tandem repeats at genome scale.

Nat Biotechnol. 2024-10

[6]
A genomic mutational constraint map using variation in 76,156 human genomes.

Nature. 2024-1

[7]
A novel quantitative targeted analysis of X-chromosome inactivation (XCI) using nanopore sequencing.

Sci Rep. 2023-8-8

[8]
Precision medicine in rare diseases: What is next?

J Intern Med. 2023-10

[9]
NanoPack2: population-scale evaluation of long-read sequencing data.

Bioinformatics. 2023-5-4

[10]
A draft human pangenome reference.

Nature. 2023-5

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索