Cytogenetic and Genome Research最新文献

Introduction: X chromosomal structural changes involving PHEX result in X-linked hypophosphatemia (XLH). However, their underlying mechanisms were poorly determined. Moreover, X chromosome inactivation (XCI) statuses in female patients with XLH remain to be studied.

Case presentation: We conducted systematic genomic analyses for a woman with XLH and detected a 3.2 Mb tandem duplication at Xp22.33, a 1.9 Mb tandem duplication at Xp22.31, and a 0.8 Mb deletion involving PHEX at Xp22.11 on the paternally derived chromosome. The fusion junctions contained templated insertions and short nucleotide additions indicative of non-homologous end joining (NHEJ) or alternative NHEJ. The patient had random XCI.

Conclusion: This study provides evidence that PHEX haploinsufficiency leads to typical XLH in women with random XCI and that a 5.9 Mb rearrangement on Xp22 permits random XCI. Our results, together with previous findings, imply that clustered structural changes due to NHEJ/alternative NHEJ are a unique type of human genomic rearrangements.

Introduction: Congenital cardiac defects are defined in cases with the deletion of the short arm of chromosome 5 and the duplication of the long arm of chromosome 4. Septal defects and patent ductus arteriosus are among the most common defects reported in the literature.

Case presentation: We reported on a case with a complex congenital cardiac defect, dysmorphic facial features, cat-like cry, hypotonia, hyporeflexia, weak swallowing and sucking, limb anomalies, and bilateral undescended testicles. A chromosomal microarray (CMA) revealed a duplication of chromosome 4q26q35.2 and a deletion of chromosome 5p15.33p14.3, originating from the balanced maternal translocation 46,XX,t(4;5)(q27;pter). Our patient showed clinical characteristics compatible with both deletion of 5p and duplication of 4q.

Conclusion: We reported a case with a rare chromosomal rearrangement. Similarities and differences between the cases in the literature are discussed. CMA is important to detect multiple copy number variations and genes may be involved. Studies are needed to investigate the genetic and/or epigenetic causes resulting in the clinical findings seen in the combination of deletion of chromosome 5p and duplication of chromosome 4q.

Introduction: Thamnophilidae (typical antbirds) are a diverse family of insectivorous passerine birds restricted to neotropical forests, encompassing 237 species, of which only 5 have been studied cytogenetically.

Methods: To investigate the chromosomal evolution of this group, we applied classical and molecular cytogenetic techniques, including conventional staining, C-banding, and fluorescence in situ hybridization with probes for repetitive telomeric sequences (TTAGGG)₅ and 18S rDNA, in two representative species: Thamnophilus caerulescens and Thamnophilus ruficapillus.

Results: The karyotypes of T. caerulescens and T. ruficapillus comprise 80 and 82 chromosomes, respectively. In addition to a possible fission in T. ruficapillus, morphological differences suggest the occurrence of pericentric inversions in the chromosomes of this species. The patterns of constitutive heterochromatin differed between the species: both showed centromeric markings and heterochromatin on the W chromosome, but T. ruficapillus also exhibited interstitial markings on seven chromosomal pairs. Both species presented interstitial telomeric sequences (ITSs) in the first seven pairs, which corresponded to constitutive heterochromatin in T. ruficapillus. The 18S rDNA probe hybridized to a single pair of microchromosomes in T. caerulescens and two pairs in T. ruficapillus.

Conclusion: This study revealed novel patterns of constitutive heterochromatin in T. ruficapillus and ITSs in both species, which have not been previously observed in Passeriformes. The correspondence between constitutive heterochromatin and ITSs in T. ruficapillus suggests that these sequences are composed of repetitive DNA highly similar to telomeric sequences and/or are remnants of pericentric inversions, whereas in T. caerulescens, other mechanisms seem to be involved. The differences in observed patterns highlight distinct chromosomal evolution between these species, emphasizing the diversity within the family Thamnophilidae and the genus Thamnophilus, in contrast to the conserved patterns typically observed in the class Aves.

Background: 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.

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Introduction: Pericentric inversions (PEIs) are rare intrachromosomal balanced structural abnormalities. To achieve complete synapsis and recombination during meiosis, the pairing of normal and inverted chromosomes requires the formation of an inversion loop. A crossover within this inversion loop leads to the production of two complementary recombinant chromosomes, which may contain both duplicated and deleted segments, including regions distal to the inversion. The clinical relevance of inverted chromosomes is significant, as they can result in the generation of recombinant gametes that may lead to early miscarriages, stillbirths, or congenital abnormalities in the progeny of carriers. The empirical frequencies of recombinant spermatozoa in men heterozygous for inv(19)(p13.3q12) were estimated. Additionally, the presence of the interchromosomal effects (ICEs) on chromosomes 13, 18, 21, X, and Y was evaluated.

Methods: Fluorescence in situ hybridization (FISH) was performed on sperm nuclei using DNA probes for the subtelomeric regions of the short (p) and long (q) arms of chromosome 19, the centromeric regions of chromosome 18, X, and Y as well as DNA probes for the regions 13q14 and 21q22.

Results: The inverted segment on chromosome 19 measures 31.5 Mb, which represents 53.3% of the total length of the affected chromosome. FISH analysis of 2,923 sperm nuclei revealed no detection of recombinant chromosomes. ICE on chromosomes 13, 18, 21, X, and Y were not observed.

Conclusion: Empirical data have been obtained for the first time regarding the frequency of gametes containing recombinant chromosomes, as well as the absence of ICEs on chromosomes 13, 18, 21, X, and Y during the meiotic segregation of the PEI of chromosome 19, inv(19)(q13.3q12). It was demonstrated that the extremely low risk of recombinant chromosome formation, falling below the detectable threshold (with 95% confidence intervals), is associated with inv(19)(p13.3q12). We hypothesize that the meiotic behavior of PEIs is influenced not only by the relative size of the inverted segment but also by the morphological characteristics of the affected chromosome. Further studies are needed to explore the factors that influence the meiotic behavior of PEIs.

Introduction: The Phasianidae family belongs to Galliformes, which is basal to other Neognathae. Despite the availability of chromosome-level genome assemblies for many Phasianidae species, the karyotypes for some species remain poorly investigated.

Methods: In this study, we described karyotypes using classical, differential, and molecular cytogenetic (BAC-FISH) methods. To compare chromosome-level genomes of 10 Galliformes species dot-plot analysis was performed.

Results: We provide the first comprehensive description of the karyotype of two Tetraonini species: the western capercaillie (Tetrao urogallus, 2n = 78) and the hazel grouse (Tetrastes bonasia, 2n = 80). We mapped chicken BAC clones (CHORI-261) with known coordinates to the chromosomes of the western capercaillie and Japanese quail (Coturnix japonica, 2n = 78) to anchor physical chromosomes to chromosome-level assemblies. Finally, we performed dot-plot comparisons of ten available chromosome-level genome assemblies to identify inter- and intrachromosomal rearrangements in Galliformes.

Conclusion: We show that the centromeric fusion of orthologs of GGA6 and GGA8 is shared by all analyzed species in the tetraonid clade: T. urogallus, T. bonasia, and Lagopus muta. We identified linage-specific intrachromosomal rearrangements on chromosomes orthologs to chicken Z (Phasianinae and Tetraoninae), 7 and 12 (Phasianinae and Tetraoninae), 5 and 13 (Perdicinae), 22 (Alectoris). Our study shows that analysis of the genomes of several closely related species allows us to identify chromosomal rearrangements characteristic of individual evolutionary lines.

The International Standing Committee on Human Cytogenomic Nomenclature (ISCN SC) considered feedback from the cytogenomics community to provide a more user friendly and organized presentation of general rules, improved example descriptions, more representative examples, and additional abbreviations. The ISCN 2024 edition represents one of the most significant reviews. Nomenclature for describing the findings of genomic mapping has been included for the first time. A key achievement of the Committee in preparing the ISCN 2024 is the provision of standardized nomenclature to ensure consistency in the ISCN description of findings irrespective of the cytogenomic technology used. This report highlights the main changes in the ISCN 2024 compared to previous editions and is a guide to assist in the transition to its implementation as the current nomenclature for describing cytogenomic findings.

Introduction: Meiotic recombination is one of the major sources of genetic diversity. Understanding the cytogenetic basis for recombination rate alterations is essential to explain the patterns of variation observed between different groups of species. Common degu (Octodon degus) is a South American rodent of the speciose and highly chromosomal variable Ctenohystrica clade, on which relatively few cytogenetic studies have been carried out. It has a mostly bi-armed karyotype, making it an interesting model for cytogenetic research.

Methods: Using immunolocalization of key meiotic proteins and electron microscopy in pachytene spermatocytes, we determined the frequency and distribution of recombination events along a number of chromosome bivalents and the characteristics of sex chromosome synapsis.

Results: Recombination rate of common degu was the highest among the Hystricognathi species studied. In contrast to most mammals, no pronounced recombination peaks near the telomeres were observed in degu. We detected late recombination nodules in the pericentromeric regions of some bivalents, which is a highly extraordinary pattern due to the centromere effect. Within the heterochromatic blocks located on the chromosome arms and marked by H3K9me3, one of the major constitutive heterochromatin marks, we observed a significant decrease in recombination frequency. We describe for the first time the bridge between X and Y in the late pachytene stage in common degu and the absence of late MLH1-dependent recombination nodules in the sex bivalent.

Conclusion: We can assume that the absence of H3K9me3 signaling at centromeres is unrelated to the presence of MLH1 near the centromere. Findings on potential achiasmatic meiosis in common degu were discussed in relation to sex chromosome evolution.