Cytogenetic and Genome Research最新文献

{"title":"Transposable elements and sex chromosome evolution in Eulimnadia texana.","authors":"Chathumadavi Ediriweera, Stephen C Weeks","doi":"10.1159/000548721","DOIUrl":"https://doi.org/10.1159/000548721","url":null,"abstract":"<p><strong>Introduction: </strong>Sex chromosomes often evolve through suppressed recombination and accumulation of transposable elements (TEs) on the sex-limited chromosome, leading to divergence and eventual degeneration. The clam shrimp Eulimnadia texana possesses proto-sex chromosomes (Z and W) at an early evolutionary stage, providing a unique opportunity to examine the initial genomic changes underlying sex chromosome differentiation. Additionally, both sex chromosomes are expressed in homogametic ZZ and WW shrimp, allowing a regular expression of both sex chromosomes in homozygotes.</p><p><strong>Methods: </strong>We analyzed newly assembled ZZ (male) and previously published WW (hermaphrodite) genomes of E. texana. Sex-linked markers were mapped to identify the Z chromosome. TEs were annotated using a species-specific repeat library and RepeatMasker. The Z and W chromosomes were divided into bins and randomization tests compared TE accumulation between the sex chromosomes as well as between corresponding regions within these two chromosomes; the latter was focused on the putative sex-determining regions of both the Z and W. Kimura distance-based analyses were used to estimate TE age divergence.</p><p><strong>Results: </strong>The Z chromosome showed no significant TE enrichment relative to autosomes but was enriched for DNA transposons. The W chromosome exhibited significantly higher retrotransposon (LTR and LINE) accumulation. Only the sex-determining region of the W showed significantly elevated retrotransposon content compared to the Z. TE age landscapes indicated recent bursts of retrotransposon activity on the W.</p><p><strong>Conclusion: </strong>These findings support theoretical predictions that retrotransposons accumulate in non-recombining regions, while DNA transposons are associated with recombining chromosomes. The W chromosome of E. texana shows early signs of differentiation, with localized retrotransposon buildup, while the Z remains autosome-like. This study highlights E. texana as a valuable model for understanding the genomic mechanisms of early sex chromosome evolution.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-24"},"PeriodicalIF":1.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191317","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":"Molecular mechanisms of proliferative senescence and genomic instability in Werner syndrome and the WRN gene network.","authors":"Martin Poot","doi":"10.1159/000548500","DOIUrl":"https://doi.org/10.1159/000548500","url":null,"abstract":"<p><strong>Background: </strong>Ageing is a general, intrinsic and progressively deleterious process that affects all cells, tissues and organs albeit at different extent and rate in each individual. The complexity and universality of its phenotypic manifestations suggest a multifactorial origin. The autosomal recessive disorder Werner syndrome likely represents a segmental progeroid disorder since patients show several, but not all phenotypes of premature ageing.</p><p><strong>Summary: </strong>Proliferative senescence of diploid cells in culture provided a model system in which ageing can be studied experimentally. Cultures of cells from patients with Werner syndrome experienced an extreme form of proliferative senescence and a clonal succession of translocations, known as variegated translocation mosaicism. In addition, Werner syndrome cells showed spontaneous deletion formation and a prolongation of and arrest in the S phase of the cell cycle. The WRN protein harbors a helicase, an exonuclease and a RecQ interaction domain. With the latter the WRN protein may interact with NBS1, RPA, MRE11, TREX1, MUTYH, POT1, TRF1, FEN-1, PAPRP-1, p97/VCP, TRF2, DNA polymerase(beta), Ku76/80, EXO-1, NEIL1, and p53, which are key to DNA damage response pathways including canonical NHEJ, homologous recombination, base excision repair and telomere maintenance. The WRN exonuclease domain is a target of WRNIP1 binding, which links WRN to resolution of stalled replication due to collision with transcription and the ATM-mediated cell cycle checkpoint. . Patients with an incomplete complement of Werner syndrome phenotypes, called atypical Werner syndrome patients, were found to carry variants in LMNA, POLD1, SPRTN, MDM2, CTC1, SAMHD1.</p><p><strong>Key messages: </strong>These findings broaden the genotypic landscape and the phenotypic spectrum of Werner syndrome. In this review potential molecular mechanisms underlying genomic instability in Werner syndrome, including chromothripsis due to asynchronous S phase traverse and telomere crises followed by bridge fusion breakage cycles are discussed. The participation of WRN in multiple gene networks is consistent with the multifactorial nature of ageing in general.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-32"},"PeriodicalIF":1.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091363","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":"Karyoevolutionary processes in Atlantic damselfishes of the genus Stegastes (Pomacentridae).","authors":"Marsílio S P Rocha, Gideão W W F Costa, Marcelo B Cioffi, Luiz A C Bertollo, Vanessa C S Oliveira, Karlla D J Amorim, Wagner F Molina","doi":"10.1159/000548331","DOIUrl":"https://doi.org/10.1159/000548331","url":null,"abstract":"<p><strong>Background: </strong>The damselfishes, an extremely diverse group of herbivorous fish, stands out as an important and ubiquitous ecological component of coral reefs. In the Western South Atlantic, the genus Stegastes is the most representative, whose evolutionary paths and taxonomic status of insular endemic species have been better evaluated. To clarify the karyotypic evolution involved in the diversification of this group, cytogenetic analyses were performed in four nominal species (S. variabilis and S. fuscus, distributed in Brazilian coastal regions; S. rocasensis and S. sanctipauli, from Rocas Atoll and São Paulo and São Pedro Archipelago) and one subspecies (S. fuscus trindadensis, from Trindade and Martim Vaz Archipelago).</p><p><strong>Results: </strong>Classical cytogenetic protocols and fluorescence in situ hybridization (FISH) with 18S and 5S rDNA probes, were used for comparative analyses. All species had 2n=48 chromosomes, with high FN values ranging from 88 to 92. Stegastes rocasensis and S. sanctipauli shared identical cytogenetic patterns, while S. f. trindadensis revealed a syntenic arrangement of 18S and 5S rDNA sites not found in S. fuscus from the Brazilian coast.</p><p><strong>Conclusion: </strong>The karyotypic evolution of Stegastes was predominantly driven by multiple pericentric inversions (and/or centromere shifts), resulting in changes in the internal organization of chromosomes. Stegastes rocasensis and S. sanctipauli have similar cytogenetical patterns, as well as S. fuscus and S. f. trindadensis indicating incipient evolutionary differentiation in insular species. Mapping other repetitive DNA sequences provided an exceptional opportunity to clarify chromosomal changes and their association with the evolutionary diversification of Stegastes species.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005926","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":"Characterization of DMRT1 variants for testis determination and differentiation in emu.","authors":"Yuki Kimura, Miki Okuno, Luisa Matiz-Ceron, Shusei Mizushima, Shoichiro Mitsukawa, Yutaka Suzuki, Takehiko Itoh, Asato Kuroiwa","doi":"10.1159/000548251","DOIUrl":"https://doi.org/10.1159/000548251","url":null,"abstract":"<p><strong>Introduction: </strong>DMRT1 on the Z chromosome is a conserved male sex-determining gene in birds. In chickens, a representative model species of Neognathae, the function of DMRT1 has been well characterized. In contrast, Palaeognathae species such as the emu possess less differentiated sex chromosomes and thus provide a valuable system for investigating avian sex determination, yet molecular studies remain limited. We investigated the timing of sex determination and the expression of key genes involved in gonadal differentiation in emu, and further characterized DMRT1 variants.</p><p><strong>Methods: </strong>Sex determination stage was identified by anatomical comparison of male and female embryonic gonads. Expression of seven genes (DMRT1, AMH, SOX9, NR5A1, FOXL2, CYP19A1, and RSPO1) was examined by mRNA-seq and RT-PCR. DMRT1 splicing variants were predicted by in silico analysis and 3' RACE was used to identify alternative polyadenylation (APA) variants.</p><p><strong>Results: </strong>The gonadal differentiation occurred at HH25-28 based on gonadal morphology. Gene expression analysis revealed emu-specific patterns not observed in chickens. Notably, RSPO1 was highly expressed in females at HH24-25, preceding DMRT1 expression in males at HH28-29, suggesting ovarian differentiation begins earlier. We identified three splicing variants and four APA variants of DMRT1, with variant 1 predominant during gonadal development.</p><p><strong>Conclusion: </strong>These findings suggest that while molecular sex differentiation mechanisms are largely conserved between Palaeognathae and Neognathae, they differ in parts. In particular, early RSPO1 expression may initiate ovarian differentiation prior to testis determination by DMRT1. The presence of emu-specific DMRT1 variants further indicates possible species-specific mechanisms in testis development.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-26"},"PeriodicalIF":1.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946244","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":"<italic>Zea mays</italic> Meiotic Spindle Ultrastructure Reveals Kinetochore-Microtubule Interface and Embedded Membrane Components.","authors":"Subin Myong, Jenna K Cosby, Brianna N Padilla, David M Opozda, Jacob D Kahn, Naima Akter, Eileen T O Apos Toole, Natalie J Nannas","doi":"10.1159/000547002","DOIUrl":"10.1159/000547002","url":null,"abstract":"<p><strong>Introduction: </strong>Spindles are microtubules-based machines whose primary function is to accurately segregate chromosomes in both mitotic and meiotic cell division. The structure of spindles is critical for their function; errors in morphology or attachment to chromosomes lead to aneuploidy, potentially resulting in disease, infertility, and lethality. Electron microscopy studies have yielded fine-detail spindle ultrastructures in many plant and animal species, but no studies have investigated the spindle of Zea mays, a critical crop, and cytogenetic model system.</p><p><strong>Methods: </strong>Here we use electron tomography (ET), reconstruction, and modeling to obtain three-dimensional, nanometer-resolution of the Z. mays meiotic spindle. Structures such as microtubules, kinetochores, vesicles, membrane channels, and nuclear envelope were modeled through a partial spindle reconstruction, and confirmed using immunostaining and live fluorescence microscopy.</p><p><strong>Results: </strong>ET revealed that maize spindles contain 8-18 kinetochore microtubules (kMTs) per kinetochore, which are approximately 776 nm in diameter and 316 nm in depth. Small ∼37 nm vesicles were identified, as well as larger (∼5 µm long, 800 nm wide) membrane structures with channels that allow spindle microtubules to pass through. These membrane channels stain positively for the ER-marker protein disulfide isomerase. Imaging of prophase meiotic cells revealed a cross-hatch microtubule arrangement in the perinuclear ring on the external surface of the nuclear envelope, which also contained type II nuclear grooves with transnuclear microtubules passing from the nucleus to the cytoplasm.</p><p><strong>Conclusions: </strong>Z. mays meiotic spindles are similar to animal counterparts with a comparable number of kMTs and pre-spindle transnuclear microtubules but also plant-specific features such as Golgi-derived vesicles to assist cell plate formation, internal ER membrane channels, and a perinuclear microtubule ring that aids spindle assembly. Maize kinetochores have an electron-diffuse ball in cup morphology that is comparable in size to Drosophila kinetochores and larger than mammalian kinetochores.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-17"},"PeriodicalIF":1.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741617","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":"Chromosomal and Cellular Insights into Sexual Reproduction and Evolution: A Special Issue Honoring Professor Oxana L. Kolomiets.","authors":"Sergey Matveevsky, Vladimir Trifonov","doi":"10.1159/000547507","DOIUrl":"10.1159/000547507","url":null,"abstract":"","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-4"},"PeriodicalIF":1.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728573","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":"Fluorescence <italic>in situ</italic> Hybridization Analysis Can Reveal Subtle Chromosomal Rearrangements in Pericentromeric Regions of Acrocentric Chromosomes in Patients with Reproductive Failure.","authors":"Yusuf Bahap, Mehmet Ali Ergun, Esra Tug, Thomas Liehr, Meral Yirmibes Karaoguz","doi":"10.1159/000547638","DOIUrl":"10.1159/000547638","url":null,"abstract":"<p><strong>Introduction: </strong>Infertility and recurrent pregnancy loss are serious health problems often associated with genetic abnormalities such as chromosomal rearrangements. Although conventional cytogenetics plays a crucial role in this kind of diagnostics, it fails to detect submicroscopic changes, especially in the pericentromeric regions of acrocentric chromosomes, which are potentially prone to rearrangement. To overcome this limitation, this study aimed to identify such subtle changes that can lead to reproductive disorders using fluorescence in situ hybridization (FISH) technique and newly developed fluorescence probes that specifically target these regions.</p><p><strong>Methods: </strong>The study group consisted of 50 couples who, despite having unprotected sexual intercourse, had been unable to conceive for more than a year or had suffered two or more miscarriages and had been unable to carry a pregnancy to term. After exclusion of cytogenetically visible chromosomal alterations, patients were subjected to FISH analysis with three newly designed probe sets that stain the centromere and pericentromere regions of acrocentric chromosomes 13 and 21 (SET-I), 14 and 22 (SET-II), and 15 (SET-III).</p><p><strong>Results: </strong>FISH analysis of SET-II and SET-III probes revealed a cryptic reciprocal translocation between chromosomes 15 and 22 in a 33-year-old male. His female cousin was also found to be a carrier of the same translocation and had a dysmorphic child due to adjacent II missegregation.</p><p><strong>Conclusion: </strong>Subtle chromosomal changes, such as reciprocal translocations in our patients, may be one of the underlying causes of unbalanced gametes in reproductive disorders. The use of three newly designed FISH probe sets may need to be considered to offer comprehensive prenatal and preimplantation genetic testing to couples with reproductive failure.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728574","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":"Genomic Imprinting: Insights into Diverse Epigenetic Regulatory Mechanisms.","authors":"Gaurav Kumar Pandey, Rajiva Raman","doi":"10.1159/000547555","DOIUrl":"10.1159/000547555","url":null,"abstract":"<p><strong>Background: </strong>Genomic imprinting is a well-known phenomenon in which certain genes are expressed in a sex-of-the-parent-specific manner, resulting in mono-allelic expression.</p><p><strong>Summary: </strong>Over the years, the diversity of mechanisms observed in imprinted gene clusters has provided a valuable model system for exploring the complexities of epigenetics, which can be extended to other cellular and disease models. This review examines these different mechanisms throughout early embryonic development and offers insights into the interactions among key players such as DNA methylation, histone modifications, and non-coding RNAs, as well as their regulatory impact on gene expression.</p><p><strong>Key message: </strong>Genomic imprinting, although being a classical genetic concept, has emerged as a model system for understanding diverse epigenetic regulatory mechanisms. This review offers an overview of such regulatory mechanisms that have been learnt over the years through studies on imprinted clusters.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-18"},"PeriodicalIF":1.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689425","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":"Meiotic Arrest and Synaptonemal Complex Failure in Infertile Men with Y Chromosome Microdeletions.","authors":"Vyacheslav B Chernykh, Elizaveta E Bragina, Lyubov F Kurilo, Maria A Pankratenkova, Anna A Kashintsova, Mikhail Yu Gabliya, Igor V Vinogradov, Irina I Vityazeva, Sergey V Bogolyubov, Victor E Spangenberg, Oxana L Kolomiets","doi":"10.1159/000547448","DOIUrl":"10.1159/000547448","url":null,"abstract":"<p><strong>Background: </strong>The Y chromosome microdeletions are common genetic cause of male infertility. Mechanisms of impaired spermatogenesis and meiosis, as well as phenotypic variability, have not been sufficiently studied.</p><p><strong>Objective: </strong>The paper provides results of the spermatogenesis and meiotic study based on the analysis of synaptonemal complex (SC) in the spermatocyte nuclei in infertile men with Y chromosome microdeletions.</p><p><strong>Materials and methods: </strong>Examined cohort consisted of 9 male patients 27-32 years old with primary infertility with non-obstructive azoospermia. The patients had a 46,XY karyotype, complete (n = 4) and partial AZFc (n = 2) deletions, and complete AZFb (n = 2) and AZFb+c (n = 1) deletions. Semen analysis was performed and assessed according to the WHO guidelines (WHO, 2010). The AZF deletions were detected by multiplex PCR, analyzing Y-specific loci in accordance with the guidelines for molecular diagnosis of the Y chromosome microdeletions. Testicular biopsy was performed by with the TESE technique. Testicular tissue fragments were assessed under a light microscope for the presence of spermatocytes, spermatids, spermatozoa, atypical and degenerating germ cells in the suspension and analyzed by histopathology. Immunostaining was performed using antibodies to the SYCP3, γH2AFX, RAD51, and MLH1 proteins.</p><p><strong>Results: </strong>In 6 examined patients, spermatocytes were found at following stages of the prophase I of meiosis: leptotene - 32.3 ± 39.4 (0-100)%, zygotene - 17.4 ± 20.1 (0-63.6)%, pachytene - 48.6 ± 38.2 (0-100)%, diplotene - 1.8 ± 2.2 (0-5.6)%. Percentage of germ cells at these stages was very close between patients with AZFb, AZFb+c, and AZFc deletions. Meiotic arrest at the zygotene stage with atypical SCs and incomplete synapsis in all nuclei was found in patient with complete AZFb+c deletion. Complete meiotic arrest at early-mid-pachytene was characterized for complete AZFc and AZFb deletions. Azoospermic patients with partial AZFc (gr/gr) deletions had incomplete meiotic arrest at the mid-pachytene stage.</p><p><strong>Conclusion: </strong>Our own and literature data indicate more severe spermatogenesis and meiosis failures in patients with AZFb+c and AZFb deletions in comparison with AZFc deletions. Meiotic arrest at early-mid-pachytene was common, but some variability was found in the severity of spermatogenesis abnormalities in patients with complete AZFc deletions that requires further research.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"237-254"},"PeriodicalIF":1.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689426","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":"Fork Stalling and Template Switching in a Complex der(6)dn with Duplication of 6q24.3qter and 6p25.3: A Case Report.","authors":"Thania Alejandra Aguayo-Orozco, Ma Guadalupe Domínguez-Quezada, Horacio Rivera, Luis E Figuera, Eduardo Esparza-García, Luis Ángel Núñez-García, Elvira Garza-González, Carlos Córdova-Fletes","doi":"10.1159/000547454","DOIUrl":"10.1159/000547454","url":null,"abstract":"<p><strong>Introduction: </strong>Partial trisomy of the 6q24qter region is a rare chromosomal disorder characterized by variable clinical features and poorly understood mechanistic origins.</p><p><strong>Case presentation: </strong>We describe a de novo complex der(6) chromosome in a patient with features consistent with partial 6q trisomy syndrome, including congenital heart disease, growth restriction, developmental delay, and dysmorphic traits. Molecular Findings: Whole-genome sequencing (WGS) identified duplications of 1.5 Mb on 6p25.3 and 23.3 Mb on 6q24.3-qter. While the 6p duplication appears benign, the phenotype is likely driven by dosage-sensitive 6q genes (ARID1B, TAB2, QKI) and possible additive effects from other duplicated genes. No parental pericentric inversion was detected by classical or molecular cytogenetics, and WGS revealed no inversion-associated breakpoints. Instead, chimeric (q-/q+) and truncated reads at the 6q junction support a replication-based origin, such as reversed template switching. FISH confirmed direct insertion of the 6q segment into 6p25.3, without a del/dup pattern typical of inversion-derived recombinants. Notably, WGS detected no direct 6p-6q junction reads but identified chimeric 6p-15q-6q reads with 2-bp microhomologies, suggesting that chromosome 15 transiently mediated the rearrangement. Interspersed telomeric sequences and flanking Alu elements were also found at both breakpoints.</p><p><strong>Conclusion: </strong>Altogether, these findings support a model in which replication fork stalling and template switching - potentially facilitated by telomere dynamics and repetitive elements - led to the formation of a recombinant-like der(6) chromosome. This case highlights the mechanistic complexity of structural rearrangements and the role of replication-based errors in shaping human genomic variation.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658673","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}