Mammalian Genome最新文献

{"title":"Correction: Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease?","authors":"Julie Williams","doi":"10.1007/s00335-026-10247-y","DOIUrl":"https://doi.org/10.1007/s00335-026-10247-y","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive full-length transcriptome atlas across multiple organs of an Indian yak breed-Arunachali.","authors":"Martina Pukhrambam, Kishor U Tribhuvan, Atrayee Dutta, Vijay Paul, Avinash Pandey, Dinamani Medhi, Mokhtar Hussain, Shubham Loat, Vijai Pal Bhadana, Suresh Dabas, Joy Das, Vijay N Waghmare, A K Mohanty, Sujay Rakshit, Mihir Sarkar","doi":"10.1007/s00335-026-10251-2","DOIUrl":"10.1007/s00335-026-10251-2","url":null,"abstract":"<p><p>Yak (Bos grunniens) is a high-altitude adapted bovine species native to the Himalayan and Tibetan plateau, thriving at elevations above 3000 m from msl under hypobaric hypoxia. Despite its remarkable physiological adaptations, a complete transcriptomic understanding across multiple organs remains limited. In this study, full-length transcriptome sequencing of 22 tissues was performed using PacBio Iso-Seq, generating over 200,000 high-quality non-redundant RNA transcripts. This dataset significantly improves yak genome annotation and reveals widespread isoform diversity, including thousands of novel transcripts and 4,319 high-confidence lncRNAs. Enrichment of key hypoxia-related pathways such as HIF-1, PI3K-Akt, AMPK, and TGF-β was observed, along with tissue-specific expression patterns in vascular, immune, and reproductive systems. These results provide a valuable multi-organ transcriptomic resource and offer new insights into the genetic mechanisms supporting high-altitude adaptation in yak.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of AI-integrated genome editing and its challenges.","authors":"Matthew Tze Jian Wong, Nur Diyana Zulkifli, Thurgashini Ravichandran, Kalidasan Vasodavan, Osama Al-Shaibah, Galib Muhammad Shahriar Himel, Anusha Achuthan, Mohana Anita Anthonysamy, Kumitaa Theva Das","doi":"10.1007/s00335-026-10248-x","DOIUrl":"10.1007/s00335-026-10248-x","url":null,"abstract":"<p><p>Artificial Intelligence (AI) is poised to revolutionize the field of genome editing by enhancing precision, efficiency, and accessibility. AI-driven approaches are already improving the design of CRISPR-based systems by enabling more accurate identification of target sequences and predicting off-target effects. Machine learning (ML) algorithms can analyze vast genomic data, as well as identify patterns and mutations that might be overlooked by traditional methods. Taking together, utilizing AI/ML tools allow for the enhancement of every step in genome editing. Recent advances also demonstrated that AI-powered tools can facilitate the simulation and modeling of genetic modifications, predicting their effects on cellular behavior and phenotypes. This allows for a more rapid prediction of the genome editing effects, without the need for wet lab. Additionally, AI can accelerate drug discovery and therapeutic development by streamlining the identification of genetic targets and optimizing gene therapies. The integration of AI with genome editing promises to democratize access to cutting-edge technologies, enabling researchers to design and plan for complex genetic modifications with minimal technical expertise. Drawing from various examples, this paper dives into the advancements and applications of AI in genome editing, its limitations, as well as future directions and opportunities in this field.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of a complex chromosomal rearrangement in a novel mouse mutant by optical genome mapping.","authors":"Gretchen Holtgrefe, Patricia A Wight","doi":"10.1007/s00335-026-10241-4","DOIUrl":"10.1007/s00335-026-10241-4","url":null,"abstract":"<p><p>Here we highlight the utilities of optical genome mapping (OGM) in determining the genomic rearrangements present in a novel transgenic mouse line (Line 781), which expresses the bacterial lacZ reporter gene under control of the mouse myelin proteolipid protein (Plp1) promoter. Hemizygous transgenic mice from Line 781 present with a mutant phenotype (documented here) which entails small body size and paws and craniofacial aberrations that are 100% penetrant, whereas their non-transgenic littermates are phenotypically normal. OGM was used to determine that the transgene sits at the intersection of an unbalanced reciprocal translocation between chromosomes 1 and 2, with deletion of approximately 3.9 (chr1) and 1.8 (chr2) Mbp from the rearranged (derivative) chromosomes, thus resulting in a monosomy over these regions in the mutant genome. As well, OGM was able to determine the number of full-length copies of transgene that integrated and their orientation. Sanger sequencing of PCR products that span a junction were used to determine the chromosomal breakpoints and transgene integration site, precisely. The complex chromosomal rearrangements in Line 781 span 38 protein-coding genes that result in the transection of 1 gene from chr1 and deletion of 33 and 4 genes from chr1 and chr2, respectively. The resulting mutant phenotype is consistent with 1q24 deletion syndrome in humans having an interstitial deletion of the syntenic region in Chr1. Thus, our mouse mutant may serve as an animal model, in future studies, to explore the molecular and cellular basis of anomalies present in patients with 1q24 deletion syndrome.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel biological function-based method for mining core genes in rare disease with limited cases.","authors":"Yongqiang Gong, Kailong Zhao, Xicheng Wang, Xi Peng, Yin Liu","doi":"10.1007/s00335-026-10249-w","DOIUrl":"10.1007/s00335-026-10249-w","url":null,"abstract":"<p><p>Conventional high - throughput sequencing data analysis methods, relying on large cohorts, are unsuitable for rare diseases with few cases and poor at explaining gene biological functions. This study proposes a biological-function-based method for mining core genes under limited-sample conditions. Using colorectal cancer (CRC) and its rare subtype signet-ring cell carcinoma (SRCC) as examples, differential expression analysis was performed separately for each SRCC sample against CRC samples. Shared genes obtained through progressive intersections were defined as the initial core gene set (List 1). Non-core genes were subjected to functional enrichment analysis, and pathway-associated genes were integrated to construct the non-core gene set. Two independent SRCC samples were subsequently used for secondary mining to obtain the final biologically significant core gene set (List 2). In addition, RankProd (RP), Robust Rank Aggregation (RRA), and an external mucinous adenocarcinoma dataset (GSE281917) were used for validation. First-round mining identified 246 core genes in SRCC, while secondary mining generated 66 and 65 biologically significant core genes from two validation samples with a high degree of overlap. RP identified 1,850 candidate genes and RRA identified 601 candidate genes, among which 64 genes overlapped with the 65 genes identified by this method. In the external mucinous adenocarcinoma dataset, first-round mining identified 144 core genes, while secondary mining generated 122 and 119 core genes with high overlap between validation samples. This method enables the identification of biologically significant core genes in rare diseases under limited-sample conditions, improves the biological interpretability of gene-mining results, demonstrates stable performance in both SRCC and external mucinous adenocarcinoma datasets, and provides a reliable experimental basis for the advancement of precision medicine in rare disease research.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide characterization of genetic diversity and breed discrimination markers in Tharparkar cattle.","authors":"Anal Bose, Nishu Bharia, Sonali Sonejita Nayak, Divya Rajawat, Pallavi Hembrom, Vijay Kumar, Sita Ram Gupta, Manjit Panigrahi","doi":"10.1007/s00335-026-10244-1","DOIUrl":"10.1007/s00335-026-10244-1","url":null,"abstract":"<p><p>Tharparkar, an indigenous milch breed from India, is known for producing high-quality milk and being able to thrive in dry and desert settings. This breed is very important for the livelihoods of rural communities. This work aimed to assess genetic diversity using double digest Restriction site-Associated DNA (ddRAD) sequencing and to identify breed-specific single nucleotide polymorphisms (SNPs) for the creation of an ultra-low-density SNP panel derived from five significant indigenous breeds of India. We genotyped 48 animals from the Livestock Research Station (LRS) in Beechwal under RAJUVAS, Bikaner (Rajasthan). After careful filtering, we got 121,554 high-quality biallelic SNPs. The population exhibited an average minor allele frequency of 0.249 ± 0.117, with the mean expected and observed heterozygosity values of 0.347 ± 0.103 and 0.291 ± 0.078, respectively. The genomic inbreeding coefficients calculated by several methodologies (F_HOM, F_UNI, F_GRM and F_ROH) varied from 0.106 to 0.125, signifying a low to moderate degree of inbreeding. The prevalence of short runs of homozygosity (0-2 Mb) indicates minimal recent inbreeding, with inbreeding mostly resulting from ancient common ancestry, perhaps due to genetic drift or founder effects. The effective population size in recent generations was approximated at 82.6. To find informative SNPs that are distinctive to each breed, we used pre-selection statistics using the TRES (Toolbox for Ranking and Evaluation of SNPs) tool. Then, we used the MAF-LD approach on a reference dataset of 260 individuals from five different Indian cow breeds. This method found 309 SNPs in 260 individuals from the reference set and 77 unique SNPs that were only found in Tharparkar. These SNPs could differentiate Tharparkar apart from other breeds in both the reference and validation datasets. These results give us important information about the genetic diversity of Tharparkar cattle, show how useful ddRAD sequencing is for detecting breed-specific SNPs and stress the necessity for targeted conservation initiatives to ensure the breed's sustainability.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell therapy for age-related macular degeneration.","authors":"Affan Shaikh, Martin F Pera","doi":"10.1007/s00335-026-10242-3","DOIUrl":"10.1007/s00335-026-10242-3","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. The disease is caused by deterioration of the retinal pigment epithelium (RPE), a tissue that plays critical roles in the support of the photoreceptors. Cell therapies to replace damaged RPE in the non-exudative form of AMD have been under development for several decades. We review the progress of cell therapy to date and highlight some promising future directions for research in this area.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.","authors":"Louisa Snape, James N Sleigh","doi":"10.1007/s00335-026-10238-z","DOIUrl":"10.1007/s00335-026-10238-z","url":null,"abstract":"<p><p>Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy arising from mutations in diverse genes that principally disrupt axons and Schwann cells. As the most distal synaptic interface of motor neurons, the neuromuscular junction (NMJ) represents a plausible but underexplored site at which such disruptions may converge to confer selective peripheral neuropathy. This review synthesises current evidence for NMJ involvement in CMT, focusing on mammalian systems, and evaluates how localised synaptic pathology relates to distal nerve dysfunction across genetic models. We outline the organisation of the mammalian NMJ and experimental approaches used to assess its dysregulation, emphasising the distinction between structural and functional denervation. Appraisal of NMJ abnormalities reported across axonal and demyelinating CMT models reveals evidence for impaired synaptic maturation, transmission and conduction failure, often prior to subsequent structural denervation and axonal degeneration. Emerging patterns indicate well-studied axonal subtypes show early, length-dependent synaptic dysfunction, whereas demyelinating forms often exhibit secondary NMJ destabilisation with ineffective axonal sprouting and reinnervation attempts. We also address methodological and interpretive considerations in NMJ studies, and consider the translational relevance of NMJ disruption as a functional readout of pathology and potential therapeutic target. Collectively, this review clarifies the NMJ as an informative, active and selective site of vulnerability in CMT, while demonstrating both the need and relevance for additional investigation in mammalian systems.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copy number evolution of conserved noncoding RNA gene families across mammals.","authors":"Zewei Yang, Zixia Huang","doi":"10.1007/s00335-026-10243-2","DOIUrl":"10.1007/s00335-026-10243-2","url":null,"abstract":"<p><p>Noncoding RNAs (ncRNAs) play essential roles in mammalian gene regulation, yet their copy number evolution across mammals remains poorly characterised. Here, using high-confidence Covariate Models (CMs) from Rfam, we applied a unified INFERNAL-based framework to systematically predict copy numbers of 588 well-curated, conserved ncRNA gene families across 60 mammalian genomes. Phylogenetic correlation tests indicated that variation in ncRNA family number and total copy numbers is largely independent of genome size, scaffold number, or assembly completeness, indicating that lineage-specific evolutionary processes, rather than genome characteristics, primarily shape ncRNA copy number diversity. Using CAFE analysis, we inferred a burst of ncRNA expansions in the eutherian ancestor, predominantly involving snRNA and H/ACA snoRNA families. In contrast, estimates of phylogenetic signals (Pagel's λ) and evolutionary rates (σ²) revealed that many miRNA families exhibit lineage-specific copy number expansions. Analysis of highly variable ncRNA families further showed frequent overlap with transposable elements and distinct duplication strategies, including tandem clustering (e.g., mir-154 and SNORA116) and dispersed distributions with regional tandem duplications (e.g., 5S_rRNA). Collectively, these results provide a comparative overview of copy number variation among conserved ncRNA families in mammals. While individual predicted copies may include pseudogenised or TE-derived loci, our analyses reveal robust evolutionary patterns at the family level and provide a foundation for future studies of ncRNA duplication and diversification.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.","authors":"Naga Pradeep Rayana, Navdeep Gogna, Mark P Krebs, Gayle B Collin, Jürgen K Naggert, Patsy M Nishina","doi":"10.1007/s00335-026-10239-y","DOIUrl":"10.1007/s00335-026-10239-y","url":null,"abstract":"<p><p>Polyunsaturated fatty acids (PUFAs) are essential for photoreceptor (PR) development, structure and function, and their availability in the outer retina is predominantly mediated by the retinal pigment epithelium (RPE), a cellular monolayer juxtaposed to the PR outer segments. Because PRs lack enzymatic machinery to generate critical PUFA intermediates from dietary precursors, they rely on the RPE to coordinate multiple steps of PUFA uptake, metabolism and export. Consequently, disruption in any of these steps perturbs PR homeostasis and compromises overall retinal health. In this review, we summarize current evidence about the genes, proteins, molecular pathways, and pathological alterations that govern the regulation of PUFA metabolism in the RPE. Data from human genetic disorders, mouse models and in vitro studies is discussed to illustrate how disruption of PUFA pathways in the RPE leads to lipid imbalance and retinal degeneration, and to highlight how these findings illuminate molecular mechanisms underlying PUFA biology. We also identify critical gaps in knowledge and unresolved questions surrounding RPE-PR PUFA metabolism and propose that addressing these gaps will be essential for advancing therapeutic strategies for retinal disease.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}