Genetic Analysis of GCA Repeats in the GLS Gene: Implications for Undiagnosed Ataxia and Spinocerebellar Ataxia 3 in Mainland China DOI Open Access

Lijing Lei,

Linliu Peng,

Linlin Wan

и другие.

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Дек. 19, 2024

Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no investigated distribution and role of Chinese individuals. The aim was investigate individuals, including undiagnosed patients for identifying causal factors, healthy controls determining normal range, ATX-ATXN3 (spinocerebellar type 3, SCA3) exploring genetic modifiers. We combined whole-genome sequencing (WGS), repeat-primed polymerase chain reaction, capillary electrophoresis (RP-PCR/CE), ExpansionHunter screen 349 1505 controls, 1236 (SCA3) from mainland China. No were detected across any samples. average number 11 (range: 8-31), 12 6-33), 6-33) patients, SCA3 respectively. intermediate repeat size (9 < ≤ 13) nonexpanded allele associated later disease onset patients. Abnormal expansions are rare population. intermediate-length sizes may influence age at (AAO) © 2024 International Parkinson Movement Disorder Society.

Язык: Английский

Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer DOI Creative Commons
Atma M. Ivancevic, David Simpson,

Olivia Joyner

и другие.

Science Advances, Год журнала: 2024, Номер 10(29)

Опубликована: Июль 17, 2024

Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying formation of these pathological remain poorly understood. Through a pan-cancer epigenomic analysis, we found primate-specific endogenous retroviruses (ERVs) are rich source enhancers displaying cancer-specific activity. In colorectal cancer other epithelial tumors, oncogenic MAPK/AP1 signaling drives activation derived from ERV family LTR10. Functional studies in revealed LTR10 elements regulate tumor-specific expression multiple genes associated with tumorigenesis, such as ATG12 XRCC4 . Within human population, individual germline somatic structural variation resulting highly mutable internal tandem repeat region, which affects AP1 binding Our findings reveal ERV-derived contribute to dysregulation response shape evolution networks.

Язык: Английский

Процитировано

10

A comprehensive tandem repeat catalog of the human genome DOI Creative Commons
Readman Chiu, Indhu‐Shree Rajan‐Babu, Jan M. Friedman

и другие.

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

Опубликована: Июнь 20, 2024

With the increasing availability of long-read sequencing data, high-quality human genome assemblies, and software for fully characterizing tandem repeats, genome-wide genotyping repeat loci on a population scale becomes more feasible. Such efforts not only expand our knowledge landscape in but also enhance ability to differentiate pathogenic mutations from benign polymorphisms. To this end, we analyzed 272 genomes assembled using datasets three public initiatives that employed different technologies. Here, report catalog over 18 million loci, many which were previously unannotated. Some these are highly polymorphic, them reside within coding sequences.

Язык: Английский

Процитировано

4

Disco‐Interacting Protein 2 Homolog B CGG Repeat Expansion in Siblings with Neurodevelopmental Disability and Progressive Movement Disorder DOI Creative Commons
Emilie T. Théberge,

Kate Durbano,

Diane Demailly

и другие.

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Abstract Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome‐wide analyses can reveal novel genotype–phenotype associations and provide a diagnosis for patients families. Objective The aim was to identify the cause severe progressive disorder phenotype in 2 affected brothers. Methods A family brothers unaffected parents had extensive phenotyping since birth. Whole‐genome long‐read sequencing methods characterized methylation status. Results Two male siblings CGG expansion 5′‐untranslated region (UTR) disco‐interacting protein homolog B ( DIP2B ) presented phenotype, including neurodevelopmental disability, dysmorphic traits, (chorea, dystonia, ataxia). Conclusions This is first report 5′‐UTR. © 2025 International Parkinson Movement Disorder Society. article has been contributed by U.S. Government employees their work public domain USA.

Язык: Английский

Процитировано

0

DIP2B CGG repeat expansion in siblings with neurodevelopmental disability and progressive movement disorder DOI Open Access
Emilie T. Théberge,

Kate Durbano,

Diane Demailly

и другие.

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

Опубликована: Июнь 5, 2024

Abstract Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with several movement disorders. Unbiased genome-wide analyses can reveal novel genotype-phenotype associations and provide a diagnosis for patients families. Objectives To identify the cause severe progressive disorder phenotype in two affected brothers. Methods A family brothers unaffected parents had extensive phenotyping natural history followed since birth. Whole-genome long-read sequencing methods were used to characterize methylation status. Results: We describe CGG expansion 5’-untranslated region DIP2B male siblings presenting including neurodevelopmental disability, dysmorphic traits, (prominent chorea, dystonia, ataxia). Conclusions This is first report attributed 5’-UTR.

Язык: Английский

Процитировано

0

Genetic Analysis of GCA Repeats in the GLS Gene: Implications for Undiagnosed Ataxia and Spinocerebellar Ataxia 3 in Mainland China DOI Open Access

Lijing Lei,

Linliu Peng,

Linlin Wan

и другие.

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Дек. 19, 2024

Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no investigated distribution and role of Chinese individuals. The aim was investigate individuals, including undiagnosed patients for identifying causal factors, healthy controls determining normal range, ATX-ATXN3 (spinocerebellar type 3, SCA3) exploring genetic modifiers. We combined whole-genome sequencing (WGS), repeat-primed polymerase chain reaction, capillary electrophoresis (RP-PCR/CE), ExpansionHunter screen 349 1505 controls, 1236 (SCA3) from mainland China. No were detected across any samples. average number 11 (range: 8-31), 12 6-33), 6-33) patients, SCA3 respectively. intermediate repeat size (9 < ≤ 13) nonexpanded allele associated later disease onset patients. Abnormal expansions are rare population. intermediate-length sizes may influence age at (AAO) © 2024 International Parkinson Movement Disorder Society.

Язык: Английский

Процитировано

0