Genomics最新文献_第7页

Geogenomic mapping of drug-resistant Mycobacterium tuberculosis from Ireland and overseas 爱尔兰和海外耐药结核分枝杆菌的地理基因组图谱。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-08 DOI: 10.1016/j.ygeno.2025.111132

Cian Ennis , Gaetan Thilliez , Ronan F. O’Toole

In this study, we performed an in-depth comparison of genome-sequenced Mycobacterium tuberculosis isolates from Ireland with isolates from other countries. The sequenced isolates from Ireland mostly belonged to Lineage 4 (64.15 %) with Lineages 2 (17.27 %), 1 (13.21 %), 3 (5.22 %), and 5 (0.15 %) also represented. Of these, Lineages 2 (47.57 %) and 4 (34.95 %) accounted for the majority of the isolates that were resistant to at least rifampicin. By performing hierarchical clustering of the genomes, we determined that many drug-resistant (DR) strains of Lineage 2 collected in Ireland belonged to larger international clusters of the bacterium that were dominant in countries that included Estonia, Georgia, Ukraine, and Moldova. Lineage 4 DR-TB strains isolated in Ireland were also commonly part of large international clusters but the major countries differed i.e. Eswatini, Germany, United Kingdom, and Mozambique. Based on single nucleotide polymorphism (SNP) analysis, there was no evidence found of widespread onward transmission of DR-TB isolates in Ireland. This indicates that a key source of DR-TB in Ireland is translocation of M. tuberculosis from countries where specific genetic clusters of drug-resistant strains are prevalent. This study has implications for interpreting future trends in TB drug resistance. As an open economy with extensive international travel connections, Ireland is sensitive to the emergence of resistant isolates of M. tuberculosis elsewhere. In addition to caution being applied with respect to TB presenting in individuals from high multi-drug resistant (MDR) TB burden countries, vigilance is also needed for TB in persons from countries where large phylogenetic clusters of DR-TB occur.

在这项研究中，我们对来自爱尔兰和其他国家的结核分枝杆菌分离株进行了深入的基因组测序比较。来自爱尔兰的测序分离株主要属于谱系4(64.15 %)，谱系2（17.27 %）、1（13.21 %）、3（5.22 %）和5（0.15 %）也有代表。其中，2号菌株（47.57 %）和4号菌株（34.95 %）至少对利福平耐药。通过对基因组进行分层聚类，我们确定在爱尔兰收集的许多耐药（DR）谱系2菌株属于在爱沙尼亚、格鲁吉亚、乌克兰和摩尔多瓦等国家占主导地位的较大的国际细菌群。在爱尔兰分离的谱系4耐药结核菌株通常也是大型国际聚集性病例的一部分，但主要国家有所不同，即斯瓦蒂尼、德国、英国和莫桑比克。根据单核苷酸多态性（SNP）分析，在爱尔兰没有发现广泛传播耐药结核分离株的证据。这表明，爱尔兰耐药结核病的一个关键来源是结核分枝杆菌从普遍存在特定耐药菌株遗传群的国家的易位。这项研究对解释结核病耐药性的未来趋势具有启示意义。作为一个拥有广泛国际旅行联系的开放经济体，爱尔兰对其他地方出现的耐药结核分枝杆菌分离株非常敏感。除了对来自耐多药结核病高负担国家的个人出现的结核病采取谨慎态度外，还需要对来自发生大量耐多药结核病聚集性病例的国家的个人出现的结核病保持警惕。

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引用次数: 0

A bioinformatics pipeline for identifying homoplasmic and heteroplasmic mitochondrial DNA SNVs in single-cell RNA-Seq datasets 在单细胞RNA-Seq数据集中鉴定同质和异质线粒体DNA snv的生物信息学管道。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-06 DOI: 10.1016/j.ygeno.2025.111122

Zhiling Guan , Patrick Lindsey , Rick Kamps , Hubert J.M. Smeets

Mitochondrial DNA (mtDNA) single nucleotide variants (SNVs) are associated with various pathologies, predominantly in energy-demanding tissues like muscles and brain. Characterizing these SNVs at the single-cell level is crucial for understanding their mechanism and clinical manifestation. Publicly available single-cell RNA sequencing (scRNA-seq) data could be an invaluable resource, but existing pipelines fall short in reliable detection of mtDNA SNVs from scRNA-seq data. Therefore, we developed a novel bioinformatics pipeline, that includes quality control, alignment to the mitochondrial genome, SNV calling, and annotation, and that filters-out sequencing errors. Coverage-dependent thresholds are customizable for detecting heteroplasmic SNVs. Duplicate reads can be retained as the majority were valid biological duplicates. Strand bias errors, exceeding a 1:3 ratio, RNA modification-induced errors, identified by the presence of multiple alternative alleles at the same position, and overrepresented SNVs were removed. Our data demonstrated that this pipeline effectively detects homoplasmic and heteroplasmic mtDNA SNVs in scRNA-Seq data.

线粒体DNA （mtDNA）单核苷酸变异（snv）与多种病理有关，主要发生在肌肉和大脑等高能量组织中。在单细胞水平上表征这些snv对于了解其机制和临床表现至关重要。公开的单细胞RNA测序（scRNA-seq）数据可能是一种宝贵的资源，但现有的管道在从scRNA-seq数据中可靠地检测mtDNA snv方面存在不足。因此，我们开发了一种新的生物信息学管道，包括质量控制、线粒体基因组比对、SNV调用和注释，并过滤掉测序错误。覆盖率相关的阈值可定制用于检测异质性snv。重复的读取可以保留，因为大多数是有效的生物重复。去除超过1:3比例的链偏置错误、RNA修饰引起的错误（通过在同一位置存在多个替代等位基因来识别）和过度代表的snv。我们的数据表明，该管道可以有效地检测scRNA-Seq数据中的同质和异质mtDNA snv。

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引用次数: 0

Elucidating the landscape of genome-wide chromatin interaction sites of the lncRNA TUG1 in bovine cell lines and liver tissue 阐明lncRNA TUG1在牛细胞系和肝组织中全基因组染色质相互作用位点的格局。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-06 DOI: 10.1016/j.ygeno.2025.111135

Rosemarie Weikard , Raghu Bhushan , Doreen Becker , Frieder Hadlich , Carole Charlier , Gabriel Costa Monteiro Moreira , Christa Kuehn

Long-noncoding RNA (lncRNA) interact with DNA, RNA and proteins to regulate the epigenome and fundamental biological processes. In the bovine genome, the nature and mechanisms of lncRNA interactions with specific chromatin regions are unexplored yet. Here, we aimed to unravel the chromatin interaction sites of the evolutionary conserved lncRNA TUG1 in the bovine genome using ChIRP-seq (chromatin isolation by RNA precipitation) in two popular bovine cell lines (MDBK, MAC-T) and liver tissue. About half of the genome-wide TUG1 chromatin occupancy in the genome (3225, 3587 and 3,977 interaction sites in MDBK, MAC-T and liver, respectively) was associated with protein-coding genes. Observation of numerous concordant TUG1 chromatin interaction sites between MDBK and MAC-T cells and liver tissue was consistent with the known ubiquitous expression of TUG1. Analysis of overlaps between ChIRP-seq peaks and ATAC-seq peaks in MDBK and MAC-T cells pinpointed TUG1 chromatin interaction sites relevant for modulating chromatin accessibility.

长链非编码RNA （lncRNA）与DNA、RNA和蛋白质相互作用，调控表观基因组和基本生物学过程。在牛基因组中，lncRNA与特定染色质区域相互作用的性质和机制尚未被探索。在这里，我们旨在利用ChIRP-seq（通过RNA沉淀分离染色质）在两种常见的牛细胞系（MDBK, MAC-T）和肝脏组织中揭示进化保守的lncRNA TUG1在牛基因组中的染色质相互作用位点。基因组中TUG1染色质占据量的一半左右（MDBK、MAC-T和肝脏中分别有3225、3587和3977个相互作用位点）与蛋白质编码基因相关。在MDBK和MAC-T细胞以及肝组织之间观察到许多一致的TUG1染色质相互作用位点，这与已知的TUG1普遍表达一致。分析MDBK和MAC-T细胞中ChIRP-seq峰和ATAC-seq峰之间的重叠，确定了与调节染色质可及性相关的TUG1染色质相互作用位点。

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引用次数: 0

Whole-genome sequence of the lichen-forming fungus Cetrariella delisei reveals an expanded repertoire of biosynthetic gene clusters 地衣形成真菌的全基因组序列揭示了生物合成基因簇的扩展库。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-03 DOI: 10.1016/j.ygeno.2025.111131

Minjoo Cho , Eunkyung Choi , Seung Jae Lee , Soyun Choi , Inseo Kim , Doyoon Shin , Wonyong Kim , Jae-Seoun Hur , Jeong-Hoon Kim , Jae-Sung Rhee , Hyun Park

Lichens represent a distinctive symbiotic relationship between fungi and photosynthetic algae, allowing them to persist in harsh and extreme habitats. While known for their adaptability, the genomic features of lichen-forming fungi remain relatively understudied. In this study, the genome of the lichen-forming fungus Cetrariella delisei was assembled into 40 contigs, spanning 45.8 Mbp, with a BUSCO completeness of 96.7 %. Repetitive sequences comprised 18.14 % of the genome. A total of 11,716 genes were annotated, including 401 putative carbohydrate-active enzymes (CAZymes), though polysaccharide lyases were absent. Comparative analysis with five additional Parmeliaceae species showed that C. delisei contains a markedly higher number of auxiliary activity genes. Notably, C. delisei harbors 79 biosynthetic gene clusters (BGCs), exceeding the 50 to 65 clusters typically observed in related species, reflecting an expanded biosynthetic repertoire potentially underlying enhanced natural product diversity. These results improve our understanding of lichen symbiosis and provide a valuable genomic resource for future research.

地衣代表了真菌和光合藻类之间独特的共生关系，使它们能够在恶劣和极端的栖息地中生存。虽然众所周知，它们的适应性，地衣形成真菌的基因组特征仍然相对较少的研究。本研究将形成地衣的真菌Cetrariella delisei基因组组装为40个contigs，全长45.8 Mbp， BUSCO完整性为96.7 %。重复序列占基因组的18.14% %。总共有11,716个基因被注释，包括401个假定的碳水化合物活性酶（CAZymes），尽管多糖裂解酶缺失。与其他5种香芹科植物的比较分析表明，delisei的辅助活性基因数量明显高于其他5种。值得注意的是，delisei拥有79个生物合成基因簇（bgc），超过了在近缘物种中通常观察到的50至65个簇，反映了扩大的生物合成库可能是增强天然产物多样性的基础。这些结果提高了我们对地衣共生的认识，并为今后的研究提供了宝贵的基因组资源。

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引用次数: 0

High-throughput characterization of 5886 HER2 variants identifies 112 new in cellulo gain-of-function mutations 5886个HER2变异体的高通量特性鉴定出112个新的细胞功能获得突变。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-02 DOI: 10.1016/j.ygeno.2025.111118

Christopher J. Giacoletto , Liz J. Valente , Lancer Brown , Sara Patterson , Rewatee Gokhale , Susan M. Mockus , Wayne W. Grody , Hong-Wen Deng , Jerome I. Rotter , Martin R. Schiller

ERBB2 (HER2) is a well-studied oncogene with several driver mutations apart from the well-known amplification defect in some breast cancers. We used the GigaAssay to test the functional effect of HER2 missense mutations on its receptor tyrosine kinase function. The GigaAssay is a modular high-throughput one-pot assay system for simultaneously measuring molecular function of thousands of genetic variants at very high accuracy. The activities of 5886 mutations were classified, significantly more mutants than previously reported. These variants include 112 new in cellulo, as well as 10 known and 9 new in vivo gain-of-function (GOF) mutations. Many of the GOFs spatially cluster in sequence and structure, supporting the activation mechanisms of heterodimerization with EGFR and release of kinase inhibition by the juxtamembrane domain. Retrospective analysis of patient outcomes from the Genomic Data Commons predicts survival with the newly identified HER2 GOF variants is better than with previously-identified GOFs, which likely represented the most severe variants.

ERBB2 （HER2）是一种被充分研究的癌基因，除了在一些乳腺癌中众所周知的扩增缺陷外，还具有几种驱动突变。我们使用GigaAssay检测HER2错义突变对其受体酪氨酸激酶功能的功能影响。GigaAssay是一种模块化的高通量单锅分析系统，可同时测量数千种遗传变异的分子功能，准确度非常高。对5886个突变的活性进行了分类，明显多于以往报道的突变体。这些变异包括112个新的细胞突变，以及10个已知的和9个新的体内功能获得（GOF）突变。许多gof在序列和结构上在空间上聚集，支持EGFR异源二聚化的激活机制和近膜结构域释放激酶抑制。来自基因组数据共享（Genomic Data Commons）的患者预后回顾性分析预测，新发现的HER2 GOF变异患者的生存率高于先前发现的GOF，后者可能代表了最严重的变异。

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引用次数: 0

Differential m6A methylation landscapes in breast and leg muscles of Zhijin white geese: Epigenetic insights into muscle development 织金白鹅胸肌和腿肌m6A甲基化的差异：肌肉发育的表观遗传学见解。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-10-01 DOI: 10.1016/j.ygeno.2025.111130

Zhonglong Zhao , Hong Yang , Yong Zhang , Shijun Li , Zhaobi Ai , Runqian Yang , Yixing Ou , Tian Wang , Li Ye , Chang Shu

Muscle growth is a crucial economic trait in poultry, influenced by a combination of environmental, nutritional, and genetic factors. N⁶-methyladenosine (m6A) modification, the most abundant form of RNA modification, has been identified in various poultry tissues. However, the m6A modification profiles during goose muscle development remain poorly understood. In this study, we characterized m6A modification profiles in breast (n = 5) and leg (n = 5) muscles of Zhijin white geese using MeRIP-seq and RNA-seq. Samples were collected from healthy 6-month-old male geese of similar body weight after euthanasia. Compared to breast muscles, leg muscles exhibited significant differences in muscle fiber morphology (cross-sectional area, diameter, and density), intramuscular fat content, and overall m6A levels (P < 0.001). Leg muscles exhibited upregulation of m6A regulators (including ALKBH5, METTL14, METTL16, and ZC3H13) (P < 0.05) and showed predominant m6A peaks in coding sequences (CDS) and 3′UTRs, with conserved RRACH motifs. Compared with breast muscles, 78 differentially methylated genes (DMGs) were identified by MeRIP-seq, including 43 hyper-methylated and 35 hypo-methylated genes in leg muscles. Integrated analysis with RNA-seq revealed 11 overlapping DMGs, comprising 7 hypo-methylated and 4 hyper-methylated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DMGs were significantly enriched in neuroactive ligand–receptor interaction, glycosaminoglycan biosynthesis, and regulation of actin cytoskeleton. Furthermore, we identified LGI1, CDK18, and LPAR2 from the significantly enriched pathways as potential candidate genes influencing muscle development. This study provides a theoretical foundation for further investigation into the regulatory role of m6A modification in goose muscle development.

家禽肌肉生长是一项重要的经济性状，受包括环境、营养和遗传因素在内的多因素调控。n6 -甲基腺苷（m6A）修饰是最丰富的RNA修饰形式，已在各种家禽组织中被发现。然而，在鹅肌肉发育过程中m6A的修饰谱仍然知之甚少。本研究利用MeRIP-seq和RNA-seq对直金白鹅胸肌（n = 5）和腿肌（n = 5）的m6A修饰谱进行了分析。从安乐死后体重相近的6月龄健康雄鹅中采集样本。在肌纤维形态（横截面积、直径、密度）、肌内脂肪含量和m6A水平上，乳房和腿部肌肉之间存在显著差异(P

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引用次数: 0

Temporal shifts and cross-site relationships of oral, gut, and vaginal microbiota during the third trimester of pregnancy 妊娠晚期口腔、肠道和阴道微生物群的时间变化和跨部位关系。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-09-30 DOI: 10.1016/j.ygeno.2025.111123

Lulu Meng , Haishan Xie , Xia Duan , Xinyuan Liang , Xiaomei Tang , Huijuan Luo , Xiaomin Xiao , Zhe Li

Background

The maternal microbiome during pregnancy influences maternal and neonatal health, yet its dynamics and cross-site relationships in the third trimester remain unclear.

Methods

Oral, fecal, and vaginal samples were collected from 22 healthy pregnant women and analyzed using 16S rRNA gene sequencing.

Results

As pregnancy progressed, gut microbial richness significantly increased, while vaginal richness significantly declined. Source tracking showed that the majority of microbes originated from their respective niches, although low-level cross-site contributions were also observed. Correlation-based network analysis revealed complex associations among microbial communities across sites. The oral microbiome exhibited distinct relative contributions and network relationships to the gut and vaginal microbiomes. Moreover, some low-abundance genera (relative abundance <1 %) played a critical role in maintaining ecological balance compared to high-abundance genera.

Conclusions

This study demonstrates dynamic, site-specific microbial changes and highlights potential microbial connections across body sites during late pregnancy, offering new ecological insights relevant to maternal–fetal health.

背景：妊娠期间母体微生物组影响孕产妇和新生儿健康，但其在妊娠晚期的动态和跨位点关系尚不清楚。方法：采集22例健康孕妇的口腔、粪便和阴道样本，采用16S rRNA基因测序进行分析。结果：随着妊娠的进展，肠道微生物丰富度显著增加，阴道微生物丰富度显著下降。来源跟踪显示，大多数微生物起源于各自的生态位，尽管也观察到低水平的跨站点贡献。基于相关性的网络分析揭示了不同站点间微生物群落之间的复杂关联。口腔微生物组与肠道和阴道微生物组表现出明显的相对贡献和网络关系。结论：本研究显示了妊娠后期体内微生物的动态、位点特异性变化，并强调了妊娠后期身体各部位之间潜在的微生物联系，为母胎健康提供了新的生态学见解。

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引用次数: 0

Evaluation of gut microbial diversity and correlation in asymptomatic and symptomatic patients with hand, foot and mouth disease 手足口病无症状和有症状患者肠道微生物多样性及其相关性评估

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-09-30 DOI: 10.1016/j.ygeno.2025.111126

Hongwei Jin , Bin Feng , Wenxiao Gong, Xiaoliang Chen, Dongli Wang, Yan Li, Weijun Huang, Wenting Peng

•
With the proposal of the concept of “metagenomics” and the development of sequencing technology, 16S rRNA gene profiling has been widely applied in the survey of microbial diversity. This study explored the gut microbiota of children with hand, foot and mouth disease (HFMD). This study investigated the gut microbiota of 24 children with asymptomatic and symptomatic hand, foot, and mouth disease (HFMD) and 19 healthy controls using 16S rRNA sequencing. The gut microbiota, both in asymptomatic and symptomatic HFMD patients, was distinct from the controls, with the composition of gut microbiota in the HFMD cases represented a significant difference. The dysbiosis of gut microbiota of the HFMD cases included a reduction of butyrate-producing bacteria and an up-regulation of inflammation-inducing bacteria. These may have impaired the intestinal biological mucosal barrier and host immune functions, promoting the invasion of the enterovirus.

•随着“宏基因组学”概念的提出和测序技术的发展，16S rRNA基因图谱在微生物多样性调查中得到了广泛的应用。本研究探讨了儿童手足口病（HFMD）的肠道微生物群。本研究采用16S rRNA测序技术，对24例无症状和有症状手足口病（手足口病）患儿和19例健康对照者的肠道菌群进行了研究。无症状和有症状手足口病患者的肠道微生物群与对照组不同，手足口病患者肠道微生物群的组成具有显著差异。手足口病患者的肠道菌群失调包括产生丁酸盐的细菌减少和诱导炎症的细菌上调。这些可能破坏了肠道生物粘膜屏障和宿主免疫功能，促进了肠道病毒的入侵。

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引用次数: 0

Trem2-dependent Insl3 regulation via Dap12-Syk-PI3K pathway: A new pathogenic mechanism in cryptorchidism 通过Dap12-Syk-PI3K途径调控trem2依赖性Insl3：隐睾的一种新的致病机制

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-09-30 DOI: 10.1016/j.ygeno.2025.111120

Songyi Ye , Chenyu Wu , Shuaijing Huang , Haowen Fan , Zhiqing Zhang , Jinling Chen , Wenliang Ge

Cryptorchidism, affecting 1 %–9 % of male neonates, represents one of the most prevalent congenital genitourinary anomalies. Studies highlighted Leydig cell derived insulin-like 3 (Insl3) as pivotal in the initial phase of testicular descent. However, the pathogenic mechanisms underlying decreased Insl3 remain poorly elucidated. Here, we showed that triggering receptor expressed on myeloid cells-2 (Trem2) acted as a central mediator in macrophage-Leydig cell communication, influencing testicular descent via Insl3 regulation. In boys with cryptorchidism, Trem2 in testes was markedly downregulated. 63.16 % of Trem2^−/− mice exhibited cryptorchidism and abnormal sperm motility and morphology, concomitant with decreased Leydig cells and Insl3. In vitro studies using human testicular cultures also revealed that Trem2 expression positively correlated with Insl3 expression. Mechanistically, ketoconazole elevated TNF-α due to suppression of the Trem2-Dap12-Syk-PI3K axis, ultimately disrupting total Leydig cell number and Insl3 expression. Collectively, these findings unveil Trem2 as a paracrine sentinel for Insl3-dependent testicular descent, thereby mitigating cryptorchidism.

隐睾，影响1 %-9 %的男性新生儿，是最普遍的先天性泌尿生殖系统异常之一。研究强调，间质细胞衍生的胰岛素样3 （Insl3）在睾丸下降的初始阶段起关键作用。然而，Insl3降低的致病机制尚不清楚。在这里，我们发现骨髓细胞上表达的触发受体-2 （Trem2）在巨噬细胞-间质细胞通讯中起中心介质作用，通过Insl3调节影响睾丸下降。在隐睾男孩中，睾丸中的Trem2明显下调。63.16 %的Trem2-/-小鼠出现隐睾、精子运动和形态异常，并伴有间质细胞和Insl3的减少。体外对人睾丸培养物的研究也显示Trem2的表达与Insl3的表达呈正相关。从机制上讲，酮康唑通过抑制Trem2-Dap12-Syk-PI3K轴而升高TNF-α，最终破坏间质细胞总数和Insl3表达。总的来说，这些发现揭示了Trem2作为insl3依赖性睾丸下降的旁分泌前哨，从而减轻了隐睾。

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引用次数: 0

Identifying and characterizing a novel APC promoter 1B deletion in a Chinese family with familial adenomatous polyposis 中国家族性腺瘤性息肉病家族中APC启动子1B缺失的鉴定和特征

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-09-30 DOI: 10.1016/j.ygeno.2025.111119

Huihan Ai , Hang Yang , Chai Luv , Guanglong Chen , Weijie Zhao , Zikun Wu , Shijun Xu , Jie Ma , Kangdong Liu , Zhi Li

Background

Typical cases of familial adenomatous polyposis (FAP) exhibit variants in the coding sequence of adenomatous polyposis coli (APC) gene coding sequence. Families without detectable APC variants can't benefit from genetic testing.

Methods

We investigated a FAP family with APC variant negativity using exome sequencing, genome sequencing. Quantitative real-time PCR, single nucleotide polymorphism analysis, sanger sequencing, and organoid drug sensitivity assays.

Results

We discovered a novel deletion spanning about 100 kb upstream of the APC transcription start site, covering the entire APC 1B promoter, in all affected members of the FAP family. The proband's blood RNA revealed the silencing of one APC allele, linked to this deletion. This deletion suppressed APC gene transcription. Additionally, this family exhibited unique extracolonic manifestations, and their response to FAP treatment drugs was similar to that of typical FAP cases. Despite this, conventional anticancer treatments led to favorable outcomes for the patients.

Conclusion

These findings indicated that APC exon variant-negative FAP patients may have deletions in the promoter region, particularly the 1B region. Their clinical features and treatment responses differ from other FAP cases, emphasizing the importance of personalized management strategies tailored to their variant profile.

背景：家族性腺瘤性息肉病（FAP）的典型病例表现为大肠腺瘤性息肉病（APC）基因编码序列的变异。没有检测到APC变异的家庭不能从基因检测中获益。方法：采用外显子组测序、全基因组测序对APC变异阴性的FAP家族进行研究。实时定量PCR、单核苷酸多态性分析、sanger测序和类器官药物敏感性分析。结果：在所有受影响的FAP家族成员中，我们发现了APC转录起始位点上游约100 kb的新缺失，覆盖了整个APC 1B启动子。先证者的血液RNA显示一个APC等位基因沉默，与这种缺失有关。这种缺失抑制了APC基因的转录。此外，该家族表现出独特的结肠外表现，其对FAP治疗药物的反应与典型FAP病例相似。尽管如此，传统的抗癌治疗对患者还是有良好的效果。结论：这些发现表明APC外显子变异阴性的FAP患者可能在启动子区域，特别是1B区域存在缺失。他们的临床特征和治疗反应与其他FAP病例不同，强调了针对其不同情况量身定制个性化管理策略的重要性。

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引用次数: 0