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为使用长读长进行短串联重复序列分析做好准备——挑战与当前技术水平

Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art.

作者信息

Chaushevska Marija, Alapont-Celaya Karmele, Schack Anne Kristine, Krych Lukasz, Garrido Navas M Carmen, Krithara Anastasia, Madjarov Gjorgji

机构信息

Faculty of Computer Science and Engineering, University Saints Cyril and Methodius, Skopje, North Macedonia.

gMendel ApS, Copenhagen, Denmark.

出版信息

Front Genet. 2025 Jul 2;16:1610026. doi: 10.3389/fgene.2025.1610026. eCollection 2025.


DOI:10.3389/fgene.2025.1610026
PMID:40672393
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12263367/
Abstract

Short tandem repeats (STRs) are repetitive DNA sequences that contribute to genetic diversity and play a significant role in disease susceptibility. The human genome contains approximately 1.5 million STR loci, collectively covering around 3% of the total sequence. Certain repeat expansions can significantly impact cellular function by altering protein synthesis, impairing DNA repair, and leading to neurodegenerative and neuromuscular diseases. Traditional short-read sequencing struggles to accurately characterize STRs due to its limited read length, which limits the ability to resolve repeat expansions, increases mapping errors, and reduces sensitivity for detecting large insertions or interruptions. This review examines how long-read sequencing technologies, particularly Oxford Nanopore and PacBio, overcome these limitations by enabling direct sequencing of full STR regions with improved accuracy. We discuss challenges in sequencing, bioinformatics workflows, and the latest computational tools for STR detection. Additionally, we highlight the strengths and limitations of different methods, providing deeper insight into the future of STR genotyping.

摘要

短串联重复序列(STRs)是有助于遗传多样性的重复性DNA序列,在疾病易感性中发挥重要作用。人类基因组包含约150万个STR位点,总计覆盖约3%的总序列。某些重复序列的扩增可通过改变蛋白质合成、损害DNA修复并导致神经退行性疾病和神经肌肉疾病,从而显著影响细胞功能。由于传统短读长测序的读长有限,难以准确表征STRs,这限制了其分辨重复序列扩增的能力,增加了映射错误,并降低了检测大插入或中断的灵敏度。本综述探讨了长读长测序技术,特别是牛津纳米孔技术和PacBio技术,如何通过对完整STR区域进行直接测序并提高准确性来克服这些限制。我们讨论了测序中的挑战、生物信息学工作流程以及用于STR检测的最新计算工具。此外,我们强调了不同方法的优势和局限性,为STR基因分型的未来提供了更深入的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c2/12263367/89dc8fa35364/fgene-16-1610026-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c2/12263367/cbad4687b74c/fgene-16-1610026-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c2/12263367/89dc8fa35364/fgene-16-1610026-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c2/12263367/cbad4687b74c/fgene-16-1610026-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c2/12263367/89dc8fa35364/fgene-16-1610026-g002.jpg

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Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art.

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本文引用的文献

[1]
A detailed analysis of second and third-generation sequencing approaches for accurate length determination of short tandem repeats and homopolymers.

Nucleic Acids Res. 2025-2-27

[2]
Repeat expansion disorders.

Pract Neurol. 2025-5-15

[3]
LongTR: genome-wide profiling of genetic variation at tandem repeats from long reads.

Genome Biol. 2024-7-4

[4]
Building a catalogue of short tandem repeats in diverse populations.

Nat Rev Genet. 2024-7

[5]
Short tandem repeats - how microsatellites became the currency of forensic genetics.

Nat Rev Genet. 2024-7

[6]
Sequencing and characterizing short tandem repeats in the human genome.

Nat Rev Genet. 2024-7

[7]
Characterization and visualization of tandem repeats at genome scale.

Nat Biotechnol. 2024-10

[8]
Resolving complex structural variants via nanopore sequencing.

Front Genet. 2023-8-16

[9]
TRcaller: a novel tool for precise and ultrafast tandem repeat variant genotyping in massively parallel sequencing reads.

Front Genet. 2023-7-18

[10]
Erratum: Haplotyping SNPs for allele-specific gene editing of the expanded huntingtin allele using long-read sequencing.

HGG Adv. 2023-6-20

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