Defining a tandem repeat catalog and variation clusters for genome-wide analyses and population databases DOI Creative Commons
Ben Weisburd, Egor Dolzhenko, Mark F. Bennett

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

Abstract Tandem repeat (TR) catalogs are important components of genotyping studies as they define the genomic coordinates and expected motifs all TR loci being analyzed. In recent years, genome-wide have used ranging in size from fewer than 200,000 to over 7 million loci. Where these overlapped, often disagreed on locus boundaries, hindering comparison reuse results across studies. Now, with multiple groups developing public databases variation large population cohorts, there is a risk that, without sufficient consensus choice definitions, use divergent will lead confusion, fragmentation, incompatibility future resources. this paper, we compare existing discuss desirable features comprehensive catalog. We then present new, richly annotated catalog designed for large-scale analyses databases. Our stratifies TRs into two groups: 1) isolated suitable copy number analysis using short read or long data 2) so-called clusters that contain within wider polymorphic regions best studied through sequence-level analysis. To clusters, novel algorithm leverages long-read HiFi sequencing group repeats surrounding polymorphisms. show human genome contains at least 25,000 complex most which span 120 bp five more TRs. Resolving sequence entire instead individually constituent leads accurate enables us profile would been missed otherwise.

Язык: Английский

Nanopore sequencing of 1000 Genomes Project samples to build a comprehensive catalog of human genetic variation DOI Creative Commons
Jonas A. Gustafson, Sophia B Gibson, Nikhita Damaraju

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 7, 2024

Less than half of individuals with a suspected Mendelian condition receive precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest using long-read sequencing (LRS) to streamline genomic testing, but the absence control datasets for variant filtering prioritization has made tertiary analysis LRS challenging. To address this, 1000 Genomes Project ONT Sequencing Consortium aims generate from at least 800 samples. Our goal is use identify broader spectrum variation so we may improve our understanding normal patterns human variation. Here, present first 100 samples, representing all 5 superpopulations 19 subpopulations. These sequenced an average depth coverage 37x sequence read N50 54 kbp, high concordance previous studies identifying single nucleotide indel variants outside homopolymer regions. Using multiple structural (SV) callers, 24,543 high-confidence SVs per genome, including shared private likely disrupt gene function as well pathogenic expansions within disease-associated repeats that were not detected short reads. Evaluation methylation signatures revealed expected known imprinted loci, samples skewed X-inactivation patterns, novel differentially methylated All raw data, processed summary statistics are publicly available, providing valuable resource genetics community discover SVs.

Язык: Английский

Процитировано

26
Forensic investigative genetic genealogy: expanding pedigree tracing and genetic inquiry in the genomic era DOI Creative Commons
Mengge Wang, Hongyu Chen,

Lintao Luo

и другие.

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Genetic genealogy provides crucial insights into the complex biological relationships within contemporary and ancient human populations by analyzing shared alleles chromosomal segments that are identical descent, to understand kinship, migration patterns, population dynamics. Within forensic science, investigative genetic (FIGG) has gained prominence leveraging next-generation sequencing technologies population-specific genomic resources, opening new avenues. In this review, we synthesize current knowledge, underscore recent advancements, discuss growing role of FIGG in genomics. been pivotal revitalizing dormant inquiries offering leads numerous cold cases. Its effectiveness relies on extensive SNP profiles contributed individuals from diverse specialized databases. Advances computational genomics growth databases have spurred a profound shift application across forensics, anthropology, DNA studies. As field progresses, is evolving nascent practice more sophisticated discipline, shaping future investigations.

Язык: Английский

Процитировано

12
Increased frequency of repeat expansion mutations across different populations DOI Creative Commons
Kristina Ibáñez,

Bharati Jadhav,

Matteo Zanovello

и другие.

Nature Medicine, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

8
Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions DOI Creative Commons
David Pellerin, Pablo Iruzubieta,

Isaac Xu

и другие.

Current Neurology and Neuroscience Reports, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 16, 2025

Язык: Английский

Процитировано

1
Detecting monogenic disorders in utero non-invasively based on fetal nucleated red blood cells highly-purified by multi-functional magnetic nanoparticles DOI
Lin Cheng, Chun Feng, Ke Wu

и другие.

Analytica Chimica Acta, Год журнала: 2025, Номер 1343, С. 343690 - 343690

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

1
NanoMnT: an STR analysis tool for Oxford Nanopore sequencing data driven by a comprehensive analysis of error profile in STR regions DOI Creative Commons
GY Park, Hyunsu An, Han Luo

и другие.

GigaScience, Год журнала: 2025, Номер 14

Опубликована: Янв. 1, 2025

Abstract Oxford Nanopore Technology (ONT) sequencing is a third-generation technology that enables cost-effective long-read sequencing, with broad applications in biological research. However, its high error rate low-complexity regions hampers short tandem repeat (STR)–related To address this, we generated comprehensive STR profile of ONT by analyzing publicly available datasets. We show the influenced not only length but also unit and flanking sequences regions. Interestingly, certain were associated higher accuracy, suggesting loci are more suitable for compared to other loci. While base quality scores substitution errors within lower than those correctly sequenced bases, such patterns observed indel errors. Furthermore, choosing most recent basecaller version using super accuracy model significantly improved accuracy. Finally, present NanoMnT, lightweight Python tool corrects data estimates allele sizes. NanoMnT leverages characteristics when estimating size exhibits superior results 1-bp- 2-bp existing tools. By integrating our findings, estimation Ax10 repeats from 55% 78% up 85% excluding unfavorable sequences. Using utility findings identifying microsatellite instability status cancer data. at https://github.com/18parkky/NanoMnT.

Язык: Английский

Процитировано

1
Identification and characterization of repeat expansions in neurological disorders: Methodologies, tools, and strategies DOI Creative Commons
Elsa Leitão, Christopher Schröder, Christel Depienne

и другие.

Revue Neurologique, Год журнала: 2024, Номер 180(5), С. 383 - 392

Опубликована: Апрель 8, 2024

Tandem repeats are a common, highly polymorphic class of variation in human genomes. Their expansion beyond pathogenic threshold is process that contributes to wide range neurological and neuromuscular genetic disorders, which over 60 have been identified date. The last few years seen resurgence repeat discovery propelled by technological advancements, enabling the identification 20 novel disorders. These expansions can occur coding or non-coding regions genes, resulting mechanisms. In this article, we review strategies, tools methods be used for efficient detection characterization known new Features prioritize include anticipation, characterized increased severity earlier onset symptoms across generations, founder effects, contribute higher prevalence rates certain populations. Classical technologies such as Southern blotting, repeat-primed polymerase chain reaction (PCR) long-range PCR still detect expansions, although they usually significant limitations linked absence sequence context. Targeted sequencing using either CRISPR-Cas9 enrichment combined with long-read adaptive nanopore sampling better but more expensive alternatives. development bioinformatics applied short-read genome data now targeted manner at genome-wide level. addition, advances, particularly optical mapping (Bionano Genomics), Oxford Nanopore Technologies (ONT) Pacific Biosciences (PacBio) HiFi sequencing, offer promising avenues expansions. Despite challenges specific DNA extraction requirements, computation resources needed interpretation, these an immense potential advance our understanding disorders improve diagnostic accuracy.

Язык: Английский

Процитировано

6
Comparative evaluation of SNVs, indels, and structural variations detected with short- and long-read sequencing data DOI Creative Commons
Shunichi Kosugi, Chikashi Terao

Human Genome Variation, Год журнала: 2024, Номер 11(1)

Опубликована: Апрель 17, 2024

Abstract Short- and long-read sequencing technologies are routinely used to detect DNA variants, including SNVs, indels, structural variations (SVs). However, the differences in quality quantity of variants detected between short- data not fully understood. In this study, we comprehensively evaluated variant calling performance long-read-based SNV, indel, SV detection algorithms (6 for 12 13 SVs) using a novel evaluation framework incorporating manual visual inspection. The results showed that indel-insertion calls greater than 10 bp were poorly by short-read-based compared algorithms; however, recall precision SNV indel-deletion similar data. with was significantly lower repetitive regions, especially small- intermediate-sized SVs, algorithms. contrast, nonrepetitive regions These findings suggest need refined strategies, such as multiple algorithms, generate more complete set short-read

Язык: Английский

Процитировано

5
The emerging role of tandem repeats in complex traits DOI
Michael Lamkin, Melissa Gymrek

Nature Reviews Genetics, Год журнала: 2024, Номер 25(7), С. 452 - 453

Опубликована: Май 7, 2024

Язык: Английский

Процитировано

5
Reliable detection of sex chromosome abnormalities by quantitative fluorescence polymerase chain reaction DOI
Camilla Mains Balle, Dorte L. Lildballe, Ivonne Bedei

и другие.

Clinical Chemistry and Laboratory Medicine (CCLM), Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Abstract Objectives Many patients with sex chromosome abnormalities (SCAs) are diagnosed late in life or remain undiagnosed, leading to delayed inadequate medical intervention and care. This study aimed develop a reliable, rapid cost-effective test for identifying SCAs using blood sample – an essential step toward establishing neonatal screening program. Methods A total of 360 samples (180 SCA patients, 180 controls) were obtained from four cross-sectional studies adult age-matched controls. Informed consent was collected, all procedures followed the Declaration Helsinki. Multiplex quantitative fluorescence polymerase chain reaction (QF-PCR) utilizing short tandem repeat (STR) X-linked segmental duplication (SD) markers performed. Results analyzed automated algorithm. Deviant results manually reviewed differentiate errors PCR process those data analysis. Following analysis QF-PCR results, method accurately identified 174 (sensitivity: 96.7 %) 171 controls (specificity: 95.0 %). Mosaic karyotypes particularly challenging diagnose. Manual reanalysis corrected false positives, achieving 100 % specificity. Conclusions is promising reliable detection samples, offering cost-effectiveness scalability. The specificity following not satisfactory. underlying technique, however, demonstrated specificity, indicating that refining algorithm would significantly reduce positive results. With further refinements, we believe this be highly suitable evaluation newborn setting.

Язык: Английский

Процитировано

0