Aberrant Short Tandem Repeats: Pathogenicity, Mechanisms, Detection, and Roles in Neuropsychiatric Disorders DOI Open Access

Y L Liu,

Kun Xia

Genes, Год журнала: 2025, Номер 16(4), С. 406 - 406

Опубликована: Март 30, 2025

Short tandem repeat (STR) sequences are highly variable DNA segments that significantly contribute to human neurodegenerative disorders, highlighting their crucial role in neuropsychiatric conditions. This article examines the pathogenicity of abnormal STRs and classifies expansion disorders(TREDs), emphasizing genetic characteristics, mechanisms action, detection methods, associated animal models. STR expansions exhibit complex patterns affect age onset symptom severity. These disrupt gene function through such as silencing, toxic gain-of-function mutations leading RNA protein toxicity, generation peptides via repeat-associated non-AUG (RAN) translation. Advances sequencing technologies—from traditional PCR Southern blotting next-generation long-read sequencing—have enhanced accuracy variation detection. Research utilizing these technologies has linked a range including autism spectrum disorders schizophrenia, contribution disease risk phenotypic expression effects on genes involved neurodevelopment, synaptic function, neuronal signaling. Therefore, further investigation is essential elucidate intricate interplay between diseases, paving way for improved diagnostic therapeutic strategies.

Язык: Английский

Technology-enabled great leap in deciphering plant genomes DOI
Lingjuan Xie, Xiaojiao Gong, Kun Yang

и другие.

Nature Plants, Год журнала: 2024, Номер 10(4), С. 551 - 566

Опубликована: Март 20, 2024

Язык: Английский

Процитировано

32
Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications DOI
Indhu‐Shree Rajan‐Babu, Egor Dolzhenko, Michael A. Eberle

и другие.

Nature Reviews Genetics, Год журнала: 2024, Номер 25(7), С. 476 - 499

Опубликована: Март 11, 2024

Язык: Английский

Процитировано

27
Long read sequencing on its way to the routine diagnostics of genetic diseases DOI Creative Commons
Giulia Olivucci, Emanuela Iovino, Giovanni Innella

и другие.

Frontiers in Genetics, Год журнала: 2024, Номер 15

Опубликована: Март 6, 2024

The clinical application of technological progress in the identification DNA alterations has always led to improvements diagnostic yields genetic medicine. At chromosome side, from cytogenetic techniques evaluating number and gross structural defects genomic microarrays detecting cryptic copy variants, at molecular level, Sanger method studying nucleotide sequence single genes high-throughput next-generation sequencing (NGS) technologies, resolution sensitivity progressively increased expanding considerably range detectable anomalies alongside Mendelian disorders with known causes. However, particular regions (i.e., repetitive GC-rich sequences) are inefficiently analyzed by standard tests, still relying on laborious, time-consuming low-sensitive approaches southern-blot for repeat expansion or long-PCR highly homologous pseudogenes), accounting least part patients undiagnosed disorders. Third generation sequencing, generating long reads improved mappability, is more suitable detection hardly accessible regions. Although recently implemented not yet clinically available, read (LRS) technologies have already shown their potential medicine research that might greatly impact yield reporting times, through translation settings. main investigated LRS concerns variants expansions, probably because evolved as rapidly those dedicated (SNV) identification: gold analyses karyotyping balanced unbalanced rearrangements, respectively, southern blot repeat-primed PCR amplification sizing expanded alleles, impaired limited been significantly advent NGS. Nevertheless, recently, accuracy provided latest product releases, tested also SNV detection, especially pseudogenes haplotype reconstruction assess parental origin alleles de novo pathogenic variants. We provide a review relevant recent scientific papers exploring diagnosis diseases its future applications routine testing.

Язык: Английский

Процитировано

18
Nanopore sequencing: flourishing in its teenage years DOI
Tianyuan Zhang, Hanzhou Li, Mian Jiang

и другие.

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

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

15
Degradation and translation of maternal mRNA for embryogenesis DOI Creative Commons
Guanghui Yang,

Qiliang Xin,

Jurrien Dean

и другие.

Trends in Genetics, Год журнала: 2024, Номер 40(3), С. 238 - 249

Опубликована: Янв. 22, 2024

Язык: Английский

Процитировано

12
Epigenomic insights into common human disease pathology DOI Creative Commons
Christopher G. Bell

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Апрель 11, 2024

Abstract The epigenome—the chemical modifications and chromatin-related packaging of the genome—enables same genetic template to be activated or repressed in different cellular settings. This multi-layered mechanism facilitates cell-type specific function by setting local sequence 3D interactive activity level. Gene transcription is further modulated through interplay with factors co-regulators. human body requires this epigenomic apparatus precisely installed throughout development then adequately maintained during lifespan. causal role epigenome pathology, beyond imprinting disorders tumour suppressor genes, was brought into spotlight large-scale sequencing projects identifying that mutations machinery genes could critical drivers both cancer developmental disorders. Abrogation providing new molecular insights pathogenesis. However, deciphering full breadth implications these changes remains challenging. Knowledge accruing regarding disease mechanisms clinical biomarkers, pathogenically relevant surrogate tissue analyses, respectively. Advances include consortia generated reference epigenomes, high-throughput DNA methylome association studies, as well ageing-related diseases from biological ‘clocks’ constructed machine learning algorithms. Also, 3rd-generation beginning disentangle complexity modification haplotypes. Cell-free methylation a biomarker has clear utility potential assess organ damage across many Finally, understanding aetiology brings it opportunity for exact therapeutic alteration CRISPR-activation inhibition.

Язык: Английский

Процитировано

10
GDBr: genomic signature interpretation tool for DNA double-strand break repair mechanisms DOI Creative Commons
Ho Cheol Ryu, Hyun Ho Han, Chuna Kim

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(2)

Опубликована: Янв. 11, 2025

Abstract Large genetic variants can be generated via homologous recombination (HR), such as polymerase theta-mediated end joining (TMEJ) or single-strand annealing (SSA). Given that these HR-based mechanisms leave specific genomic signatures, we developed GDBr, a signature interpretation tool for DNA double-strand break repair using high-quality genome assemblies. We applied GDBr to draft human pangenome reference. found 78.1% of non-repetitive insertions and deletions 11.0% complex substitutions contained signatures. Of these, interpreted 98.7% 1.3% the were TMEJ SSA, respectively, all TMEJ. Since population-level datasets are being dramatically accumulated, provide mechanistic insights into how formed. is available on GitHub at https://github.com/Chemical118/GDBr.

Язык: Английский

Процитировано

1
Application of high-throughput sequencing technologies and analytical tools for pathogen detection in urban water systems: Progress and future perspectives DOI
Yanmei Zhao, Fang Huang, Wenxiu Wang

и другие.

The Science of The Total Environment, Год журнала: 2023, Номер 900, С. 165867 - 165867

Опубликована: Июль 28, 2023

Язык: Английский

Процитировано

19
Advances in long-read single-cell transcriptomics DOI Creative Commons

Pallawi Kumari,

Manmeet Kaur, Kiran Dindhoria

и другие.

Human Genetics, Год журнала: 2024, Номер 143(9-10), С. 1005 - 1020

Опубликована: Май 24, 2024

Abstract Long-read single-cell transcriptomics (scRNA-Seq) is revolutionizing the way we profile heterogeneity in disease. Traditional short-read scRNA-Seq methods are limited their ability to provide complete transcript coverage, resolve isoforms, and identify novel transcripts. The protocols developed for long-read sequencing platforms overcome these limitations by enabling characterization of full-length techniques initially suffered from comparatively poor accuracy compared short read scRNA-Seq. However, with improvements accuracy, accessibility, cost efficiency, long-reads gaining popularity field This review details advances scRNA-Seq, an emphasis on library preparation downstream bioinformatics analysis tools.

Язык: Английский

Процитировано

6
A haplotype-like, chromosome-level assembled and annotated genome of Biomphalaria glabrata, an important intermediate host of schistosomiasis and the best studied model of schistosomiasis vector snails DOI Creative Commons
Daibin Zhong, Lijing Bu, Mohamed R. Habib

и другие.

PLoS neglected tropical diseases, Год журнала: 2024, Номер 18(2), С. e0011983 - e0011983

Опубликована: Фев. 29, 2024

Schistosomiasis is one of the world’s most devastating parasitic diseases, afflicting 251 million people globally. The Neotropical snail Biomphalaria glabrata an important intermediate host human blood fluke Schistosoma mansoni and a predominant model for schistosomiasis research. To fully exploit this biomedical research, here we report haplotype-like, chromosome-level assembled annotated genome homozygous iM line B . that developed at University New Mexico. Using multiple sequencing platforms, including Illumina, PacBio, Omni-C sequencing, 18 sequence contact matrices representing haploid chromosomes (2n = 36) were generated (337x coverage), 96.5% scaffold sequences anchored to chromosomes. Protein-coding genes (n 34,559), non-coding RNAs 2,406), repetitive elements (42.52% genome) predicted whole genome, detailed annotations individual also provided. genomic resource, have investigated structure organization Toll-like receptor ( TLR ) fibrinogen-domain containing protein FReD genes, two immune-related gene families. Notably, TLR-like are scattered on 13 In contrast, almost all (39 40) fibrinogen-related FREPs (immunoglobulin superfamily (IgSF) + fibrinogen (FBG)) clustered within 5-million nucleotide region chromosome 13, yielding insight into mechanisms involved in diversification This first vector snails has been level, annotated, analyzed. It serves as valuable resource deeper understanding biology snails, especially snails.

Язык: Английский

Процитировано

5