Chromosome Structure Research Articles

The relationship of maternal polymorphisms of genes related to meiosis and DNA damage repair with fetal chromosomal stability.

To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality. This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot. All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were<35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25-0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27-0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31-20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42-0.91), p=0.02]. For thefetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually). For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women.

Circuit Optimization Using a Generalized Modification of the Genetic Algorithm

The solution to the problem of circuit optimization is obtained on the basis of a combination of a genetic algorithm (GA) and the idea of generalized optimization, developed earlier for the deterministic case. It is shown that such a GA modification allows one to overcome premature convergence to local minima and to increase the minimization accuracy by several orders of magnitude. In this case, GA forms a set of populations determined by the fitness function, given in different way, depending on the strategy chosen within the framework of the idea of generalized optimization. The way of setting fitness functions as well as the length and structure of chromosomes, are determined by a control vector artificially introduced within the framework of generalized optimization. This vector determines the number of independent variables of the optimization problem and the method for calculating the fitness function. It allows you to build compound strategies that significantly increase the accuracy of the resulting solution. This, in turn, makes it possible to reduce the number of generations required during the operation of the GA and minimize the processor time for solving the problem of circuit optimization. © 2023 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.

TCP Transcription Factors in Pineapple: Genome-Wide Characterization and Expression Profile Analysis during Flower and Fruit Development

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors contain specific a basic helix–loop–helix structure, which is a significant factor in the regulation of plant growth and development. TCP has been studied in several species, but no pineapple TCP has been reported to date. Whether they are involved in the development of the flower and fruit in the pineapple remains unclear. In this study, nine non-redundant pineapple TCPs (AcTCPs) were identified. Chromosomal localization, phylogenetics, gene structure, motifs, multiple-sequence alignment, and covariance on AcTCP family members were analyzed. Analysis of promoter cis-acting elements illustrated that the AcTCP gene may be mainly co-regulated by light signal and multiple hormone signals. Analysis of expression characteristics showed a significant increase in AcTCP5 expression at 12 h after ethylene treatment, and significantly higher levels of AcTCP8 and AcTCP9 expression in the pistil than in other floral organs. Meanwhile, the AcTCP4, AcTCP5, AcTCP6, AcTCP7, and AcTCP9 expression levels were downregulated at later stages of fruit development. Transcription factors that may interact with TCP protein in the regulation of flower and fruit development are screened by the protein interaction prediction network, AcTCP5 interacts with AcSPL16, and AcTCP8 interacts with AcFT5 and AcFT6 proteins, verified by Y2H experiments. These findings provide a basis for further exploration of the molecular mechanisms and function of the AcTCP gene in flower and fruit development.

Long-read sequencing reveals the complex structure of extra dic(21;21) chromosome and its biological effects

Complex congenital chromosome abnormalities are rare but often cause severe symptoms. However, the structures and biological impacts of such abnormalities have seldomly been analyzed at the molecular level. Previously, we reported a Japanese female patient with severe developmental defects. The patient had an extra dicentric chromosome 21 (chr21) consisting of two partial chr21 copies fused together within their long arms along with two centromeres and many copy number changes. In this study, we performed whole-genome, transcriptional, and DNA methylation analyses, coupled with novel bioinformatic approaches, to reveal the complex structure of the extra chromosome and its transcriptional and epigenetic changes. Long-read sequencing accurately identified the structures of junctions related to the copy number changes in extra chr21 and suggested the mechanism of the structural changes. Our transcriptome analysis showed the overexpression of genes in extra chr21. Additionally, an allele-specific DNA methylation analysis of the long-read sequencing data suggested that the centromeric region of extra chr21 was hypermethylated, a property associated with the inactivation of one centromere in the extra chromosome. Our comprehensive analysis provides insights into the molecular mechanism underlying the generation of the extra chromosome and its pathogenic roles.

Ultrastructure and fractal property of chromosomes in close-to-native yeast nuclei visualized using X-ray laser diffraction

Genome compaction and activity in the nucleus depend on spatiotemporal changes in the organization of chromatins in chromosomes. However, the direct imaging of the chromosome structures in the nuclei has been difficult and challenging. Herein, we directly visualized the structure of chromosomes in frozen-hydrated nuclei of budding yeast in the interphase using X-ray laser diffraction. The reconstructed projection electron density maps revealed inhomogeneous distributions of chromosomes, such as a 300 nm assembly and fibrous substructures in the elliptic-circular shaped nuclei of approximately 800 nm. In addition, from the diffraction patterns, we confirmed the absence of regular arrangements of chromosomes and chromatins with 400–20 nm spacing, and demonstrated that chromosomes were composed of self-similarly assembled substructural domains with an average radius of gyration of 58 nm and smooth surfaces. Based on these analyses, we constructed putative models to discuss the organization of 16 chromosomes, carrying DNA of 4.1 mm in 800 nm ellipsoid of the nucleus at the interphase. We anticipate the structural parameters on the fractal property of chromosomes and the experimental images to be a starting point for constructing more sophisticated 3D structural models of the nucleus.

CYTOGENETIC VARIABILITY OF THE HUTSUL BREED OF HORSES

Goal. Study of features of karyotypic variability of Hutsul horses. Methods. Cytogenetic analysis, micronucleus test. Results. The average rate of genomic disorders (aneuploidy) was 10.8%, with a range of values of this variability of 8.8%–11.1% in animals of the LLC "Krai Neba" and the National Nature Park "Hutsulshchyna" with a statistically insignificant difference between the mean values. The multiple increase in the number of chromosomes, polyploidy, was in the range of 1.1%–2.0%, which does not exceed the species of this variability. The magnitude of the asynchronous divergence of the centromeric regions of the chromosomes was 2.0%–6.0%, which corresponds to the spontaneous level for horses as a whole (2.2%–9.1%). Structural chromosome abnormalities (chromosomal breaks) in the horses of the Krai Neba LLC farm were not detected, and in the animals of the Hutsulshchyna National Nature Park they were 1.1%. The range of variability of lymphocytes with a micronucleus for animals of two farms was 4.0–4.2‰. The number of dinuclear lymphocytes (6.2‰) exceeded the mitotic index (4.3‰) with an insignificant difference in the average values, which indicates the absence of radionuclide contamination of the territory. Conclusions. The average number of aneuploid cells – 10.8%, polyploid – 1.4%, asynchronous divergence of the centromeric regions of chromosomes – 3.9% and the proportion of chromosomal breaks – 1.1%. The proportion of lymphocytes with a micronucleus – 4.0–4.2–4, dinuclear lymphocytes – 6.2‰ and the mitotic index – 4.3‰, which indicates the stability of the karyotype of the studied horses.

Polyploidy Phenomenon as a Cause of Early Miscarriages in Abortion Materials.

Chromosomal abnormalities are an important cause of especially early miscarriages. The aim of this study was to analyze the chromosomal aberrations and determine the frequencies of numerical and structural chromosome abnormalities in spontaneous abortion materials. This was a prospective research and ninety two abortion samples obtained from women who had one or more miscarriages were included in the study. Conventional karyotype analysis was performed on each sample to identify possible chromosomal abnormalities. By karyotype analysis, 11 polyploidy cases, (9 triploids and 2 tetraploids), 8 trisomies (one of which was mosaic), 2 monosomies (monosomy X), 1 isochromosome, 1 Xq deletion, and 4 translocations were detected in abortion materials. Isochromosome and Xq deletion cases were also mosaic. In addition, five polymorphic variants were revealed. We found higher paternal age in polyploidy cases. The most common anomaly we found in abortion materials was polyploidy. This was followed by aneuploidy (trisomy and monosomy). Polyploidy (triploidy or tetraploidy) emerged as an important cause in cases of spontaneous abortion. Paternal age may be associated with polyploidy especially triploidy.

Identification of Shaker Potassium Channel Family Members in Gossypium hirsutum L. and Characterization of GhKAT1aD.

K+ channels of the Shaker family have been shown to play crucial roles in K+ uptake and transport. Cotton (Gossypium hirsutum) is an important cash crop. In this study, the 24 Shaker family genes were identified in cotton. Phylogenetic analysis suggests that they were assigned to five clusters. Additionally, their chromosomal location, conserved motifs and gene structure were analyzed. The promoter of cotton Shaker K+ channel genes comprises drought-, low-temperature-, phytohormone-response elements, etc. As indicated by qRT-PCR (quantitative real-time PCR), cotton Shaker K+ channel genes responded to low K+ and NaCl, and especially dehydration stress, at the transcript level. Moreover, one of the Shaker K+ channel genes, GhKAT1aD, was characterized. This gene is localized in the plasma membrane and is predicted to contain six transmembrane segments. It restored the growth of the yeast mutant strain defective in K+ uptake, and silencing GhKAT1a via VIGS (virus-induced gene silencing) resulted in more severe symptoms of K+ deficiency in cotton leaves as well as a lower net K+ uptake rate. The results of this study showed the overall picture of the cotton Shaker K+ channel family regarding bioinformatics as well as the function of one of its members, which provide clues for future investigations of cotton K+ transport and molecular insights for breeding K+-efficient cotton varieties.

Meiotic behavior of two grapevine somatic mutants with ornamental potential

‘Niagara Steck’ and ‘Niagara Variegada’ are two grapevine varieties that arose spontaneously as somatic mutants of ‘Niagara Rosada’. Berries characterize ‘Niagara Steck’ at young stages exhibiting a remarkable brown reticulated structure on the epidermis which develops into a brown-bronze russet-like structure as the berries ripe. The mature berries have strongly acidic flesh. ‘Niagara Variegada’ shows notable variegation in leaves and berries. Meiotic studies were carried out to ascertain if the mutant phenotypes could be related to any change in chromosome number, structure or other irregularity. Floral buds of both varieties at different developmental stages were collected and fixed for cytological analyses. Chromosome counts at diakinesis/metaphase I showed n=19 bivalents for both varieties. Univalent, trivalent, tetravalent chromosomes or chain configuration were not recorded ruling out the possibility of any alteration in the chromosome number or structure in both mutant varieties. However, low percentages of meiotic irregularities were recorded such as chromosome stickiness, laggards, non-oriented chromosomes, precocious chromosome segregation, tetrads with one microcyte, microspore fusion, and tetrad degeneration. The total percentage of abnormalities was higher in ‘Niagara Variegada’ (19.68%) than in ‘Niagara Steck’ (14.40%) which may have contributed to a lower percentage of pollen fertility (79.80%) when compared to ‘Steck’ (90.74%). The aforementioned varieties can be propagated by hardwood cuttings and constitute an interesting option for ornamentation of home backyards, patios, and gardens with the advantage that ‘Niagara Variegada’ bearing sweet edible berries.

Identification of VPS34-PI(3)P-FEN1-mediated DNA repair pathway as a potential drug target to overcome chemoresistance

Intrinsic or acquired chemoresistance represents a major obstacle in cancer treatment. Multiple mechanisms can contribute to cancer cells' resistance to chemotherapy. Among them, an aberrantly strengthened DNA repair mechanism is responsible for a large proportion of drug resistance to alkylating agents and radiation therapy. In cancer cells, damping overactivated DNA repair system can overcome survival advantages conferred by chromosomal translocations or mutations and lead to cytostatic effects or cytotoxic. Therefore, selectively targeting DNA repair system in cancer cells holds promise for overcoming chemoresistance.In this study, we revealed that the endonuclease Flap Endonuclease 1 (FEN1), essential for DNA replication and repair, directly interacts with phosphatidylinositol 3-phosphate [PI(3)P], and FEN1-R378 is the primary PI(3)P-binding site. PI(3)P-binding deficient FEN1 mutant (FEN1-R378A) cells exhibited abnormal chromosomal structures and were hypersensitized to DNA damage. The PI(3)P-mediated FEN1 functionality was essential for repairing DNA damages caused by multiple mechanisms. Furthermore, VPS34, the major PI(3)P synthesizing enzyme, was negatively associated with patients' survival in various cancer types, and VPS34 inhibitors significantly sensitized chemoresistant cancer cells to genotoxic agents.These findings open up an avenue for counteracting chemoresistance by targeting VPS34-PI(3)P-mediated DNA repair pathway, and call for assessing the efficacy of this strategy in patients suffering from chemoresistance-mediated cancer recurrence in clinical trials.

Homoeologous evolution of the allotetraploid genome of Poa annua L.

BackgroundPoa annua (annual bluegrass) is an allotetraploid turfgrass, an agronomically significant weed, and one of the most widely dispersed plant species on earth. Here, we report the chromosome-scale genome assemblies of P. annua’s diploid progenitors, P. infirma and P. supina, and use multi-omic analyses spanning all three species to better understand P. annua’s evolutionary novelty.ResultsWe find that the diploids diverged from their common ancestor 5.5 – 6.3 million years ago and hybridized to form P. annua ≤ 50,000 years ago. The diploid genomes are similar in chromosome structure and most notably distinguished by the divergent evolutionary histories of their transposable elements, leading to a 1.7 × difference in genome size. In allotetraploid P. annua, we find biased movement of retrotransposons from the larger (A) subgenome to the smaller (B) subgenome. We show that P. annua’s B subgenome is preferentially accumulating genes and that its genes are more highly expressed. Whole-genome resequencing of several additional P. annua accessions revealed large-scale chromosomal rearrangements characterized by extensive TE-downsizing and evidence to support the Genome Balance Hypothesis.ConclusionsThe divergent evolutions of the diploid progenitors played a central role in conferring onto P. annua its remarkable phenotypic plasticity. We find that plant genes (guided by selection and drift) and transposable elements (mostly guided by host immunity) each respond to polyploidy in unique ways and that P. annua uses whole-genome duplication to purge highly parasitized heterochromatic sequences. The findings and genomic resources presented here will enable the development of homoeolog-specific markers for accelerated weed science and turfgrass breeding.

Haplotype-specific chromosome painting provides insights into the chromosomal characteristics in self-duplicating autotetraploid sugarcane

Whole genome duplication (WGD) has long been recognized as an important driving force in plant evolution and diversification. Cytogenetic studies on allopolyploids formed by synthetic and natural WGD have reported small and large-scale changes, including structural and numerical chromosome rearrangements. However, the high similarity of homologous copies makes it difficult to find robust DNA probes for investigating whether each homologous copy undergoes chromosomal aberrations after whole-genome doubling in autopolyploid. In this study, we discovered and characterized a spontaneously doubling autotetraploid sugarcane AP85–441, which provided an opportunity for studying the evolutionary fate of chromosomes in autopolyploids after WGD. Then, a set of haplotype-specific oligo-fluorescence in situ hybridization (FISH) probes was developed based on the autotetraploid sugarcane AP85–441 genome. These probes can be used to unambiguously identify chromosome 8 homologous copies 8A, 8B, 8C, and 8D in a cell. Interestingly, a haplotype genome assembly error (approximately 12.26 Mb) was found between 8A and 8C homologous copies by haplotype-specific oligo-FISH. The haplotype-resolved karyotype was also established for the first time. By comparative FISH assay, no chromosomal aberrations were observed between AP85–441 and spontaneously doubled AP85–441 at the cytogenetic level, which suggested that the duplication of each homologous chromosome copy was strictly regulated in autotetraploid sugarcane following WGD. This study successfully applied the haplotype-specific FISH technology to autotetraploid sugarcane for the first time, and further application may bring us deep insights into the genetic mechanism of 2 n + n chromosome transmission associated with accelerated the restoration of a high sugar content in sugarcane breeding.

P-736 Balanced cryptic chromosomal rearrangement carriers detection by optical genome mapping (OGM)

Abstract Study question To evaluate diagnosis value of optical genome mapping (OGM) for potential preimplantation genetic testing in chromosomal structural rearrangement (PGT-SR) patients with cryptic chromosomal rearrangement. Summary answer OGM is an efficient method for cryptic chromosomal rearrangement detection. However, SVs near telomere and centromere regions could hardly be reported with this method. What is known already About 5∼10% infertility or sterility people carry balanced chromosomal structural variations (SVs) with high risks of miscarriage and birth defects resulting from imbalanced gametes when producing fetus. However, some balanced cryptic SVs with specific location or small fragments cannot be detected by traditional cytogenetic techniques like G-banding testing or CNV-seq. Currently, several optimized techniques are able to detect typically cryptic structural abnormality. OGM, the molecular genetic detection technique relying on new principle in recent years, have overcome the shortcomings of former techniques and are potentially capable to detect both routine and cryptic SVs well. Study design, size, duration From 2019 to 2022, 12 couples in The First Affiliated Hospital of Sun Yat-sen University and The First People’s Hospital of Yunnan Province with history of offspring birth defect, recurrent unexplained recurrent miscarriage or unexpected copy number variation in embryos from previous PGT cycles were included for diagnosis or re-analysis. Participants/materials, setting, methods Peripheral blood lymphocytes from these patients were collected and detected by OGM or traditional karyotype analysis(G-400 banding), FISH, CNV-seq, third generation sequencing(Nanopore). The results of traditional genetic test and OGM were compared to evaluate the accuracy of OGM detection of chromosomal structure vatiation. Main results and the role of chance In the 11 couples bearing adverse pregnancy or childbirth defect with normal karyotype by G-banding, OGM discovered novel chromosome translocations or inversion in 9 couples (81.81%). In 1 couple with t(4:17)(q12;p13) diagnosed by G-banding, OGM detect an additional chromosomal translocation of t(17;19)(q12;p13), which produced the repeated CNVs in chromosome19 observed in embryos from two previous PGT cycles. For small fragment translocation, terminal translocation and inversion, OGM is able to detected balanced structure abnormal of 500kbs. The OGM diagnosis were confirmed by FISH or third generation sequencing (Nanopore) or embryo mutation. The breaking position reported by OGM and Nanopore were comparable. In sum, OGM reported further information of balanced SVs in 83.33% (10/12) potential patients with duplication and depletion in embryos or abortus. Limitations, reasons for caution Due to the limitation of principle, the structural abnormalities of some special locations (centromere, secondary constriction, etc.) cannot be detected. OGM has high sensitivity and many mutations, which requires examiners to have strong ability to analyze results and genetic counseling. The price of OGM also limits the promotion and application. Wider implications of the findings OGM can provide more precious result for SVs, and PGT-SR can definitely improve the outcome of certain population with cryptic chromosomal rearrangements. The shortcoming of OGM has not been overcame yet, so it is suggested as auxiliary method beside conventional G-binding in certain circumstances in ART population. Trial registration number Not applicable

Genome-wide identification and comparative in-silico characterization of β-galactosidase (GH-35) in ascomycetes and its role in germ tube development of Aspergillus fumigatus via RNA-seq analysis.

β-galactosidase (Lactase), an enzyme belonging to the glycoside hydrolase family causing the hydrolysis and trans-glycosylation of β-D-galactosides, has a vital role in dairy industries. The current investigation emphasizes on in-silico identification and comparative analysis of different fungal lactases present in Aspergillus fumigatus, Aspergillus oryzae, Botrytis cinerea, and Fusarium fujikuroi. Prediction of motifs and domains, chromosomal positioning, gene structure, gene ontology, sub-cellular localization and protein modeling were performed using different bioinformatics tools to have an insight into the structural and functional characteristics of β-galactosidases. Evolutionary and homology relationships were established by phylogenetic and synteny analyses. A total of 14 β-gal genes (GH-35) were identified in these species. Identified lactases, having 5 domains, were predicted to be stable, acidic, non-polar and extracellularly localized with roles in polysaccharide catabolic process. Results showed variable exonic/intronic ratios of the gene structures which were randomly positioned on chromosomes. Moreover, synteny blocks and close evolutionary relationships were observed between Aspergillus fumigatus and Aspergillus oryzae. Structural insights allowed the prediction of best protein models based on the higher ERRAT and Q-MEAN values. And RNA-sequencing analysis, performed on A. fumigatus, elucidated the role of β-gal in germ tube development. This study would pave the way for efficient fungal lactase production as it identified β-gal genes and predicted their various features and also it would provide a road-way to further the understanding of A. fumigatus pathogenicity via the expression insights of β-gal in germ tube development.

Investigation of the potential role of fusicoccin, a fungal phytotoxin, in mitigating salt stress in onion roots

Fusicoccin is a diterpene glycoside that plays an important role in the regulation of plant growth and development. Fusicoccin produced by Fusicoccum amydali fungus is known to affect plant growth positively with external applications due to its potential to stimulate the tolerance system of plants under stress conditions. In this study, it was aimed to reduce the negative effects of salt (0.15 M NaCl) stress on the germination and growth of onion (Allium cepa L.) bulbs by external fusicoccin (3 µM) application. For this purpose, the germination percentage, root length, root number, fresh weight, mitotic activity, micronucleus frequency, chromosomal abnormality, antioxidant enzyme activity, osmolyte accumulation, cell membrane damage and root anatomical structure were investigated in the current study. Salt stress caused a statistically significant difference (p < 0.05) in all examined parameters. External application of fusicoccin to onion bulbs germinated under salt stress conditions was found to be promising as a plant growth promoter and mitosis stimulator. In addition, fusicoccin application alleviated the harmful effects of salt stress on the chromosome structure and root anatomical structure and protected the cells from the cytotoxic and genotoxic effects of salt. Moreover, this application contributed to the fight against reactive oxygen species of onion plant and increased salt tolerance by regulating the accumulation of osmolyte substances such as proline and antioxidant enzymes such as superoxide dismutase and catalase, and by minimizing cell membrane damage in root cells. In conclusion, this study showed that exogenous application of 3 µM fusicoccin reduced the damage caused by oxidative stress in onion bulbs and served for healthy germination and growth.

Compositional Structure of the Genome: A Review.

As the genome carries the historical information of a species' biotic and environmental interactions, analyzing changes in genome structure over time by using powerful statistical physics methods (such as entropic segmentation algorithms, fluctuation analysis in DNA walks, or measures of compositional complexity) provides valuable insights into genome evolution. Nucleotide frequencies tend to vary along the DNA chain, resulting in a hierarchically patchy chromosome structure with heterogeneities at different length scales that range from a few nucleotides to tens of millions of them. Fluctuation analysis reveals that these compositional structures can be classified into three main categories: (1) short-range heterogeneities (below a few kilobase pairs (Kbp)) primarily attributed to the alternation of coding and noncoding regions, interspersed or tandem repeats densities, etc.; (2) isochores, spanning tens to hundreds of tens of Kbp; and (3) superstructures, reaching sizes of tens of megabase pairs (Mbp) or even larger. The obtained isochore and superstructure coordinates in the first complete T2T human sequence are now shared in a public database. In this way, interested researchers can use T2T isochore data, as well as the annotations for different genome elements, to check a specific hypothesis about genome structure. Similarly to other levels of biological organization, a hierarchical compositional structure is prevalent in the genome. Once the compositional structure of a genome is identified, various measures can be derived to quantify the heterogeneity of such structure. The distribution of segment G+C content has recently been proposed as a new genome signature that proves to be useful for comparing complete genomes. Another meaningful measure is the sequence compositional complexity (SCC), which has been used for genome structure comparisons. Lastly, we review the recent genome comparisons in species of the ancient phylum Cyanobacteria, conducted by phylogenetic regression of SCC against time, which have revealed positive trends towards higher genome complexity. These findings provide the first evidence for a driven progressive evolution of genome compositional structure.

QuarTeT: a telomere-to-telomere toolkit for gap-free genome assembly and centromeric repeat identification.

A high-quality genome is the basis for studies on functional, evolutionary, and comparative genomics. The majority of attention has been paid to the solution of complex chromosome structures and highly repetitive sequences, along with the emergence of a new 'telomere-to-telomere (T2T) assembly' era. However, the bioinformatic tools for the automatic construction and/or characterization of T2T genome are limited. Here, we developed a user-friendly web toolkit, quarTeT, which currently includes four modules: AssemblyMapper, GapFiller, TeloExplorer, and CentroMiner. First, AssemblyMapper is designed to assemble phased contigs into the chromosome-level genome by referring to a closely related genome. Then, GapFiller would endeavor to fill all unclosed gaps in a given genome with the aid of additional ultra-long sequences. Finally, TeloExplorer and CentroMiner are applied to identify candidate telomere and centromere as well as their localizations on each chromosome. These four modules can be used alone or in combination with each other for T2T genome assembly and characterization. As a case study, by adopting the entire modular functions of quarTeT, we have achieved the Actinidia chinensis genome assembly that is of a quality comparable to the reported genome Hongyang v4.0, which was assembled with the addition of manual handling. Further evaluation of CentroMiner by searching centromeres in Arabidopsis thaliana and Oryza sativa genomes showed that quarTeT is capable of identifying all the centromeric regions that have been previously detected by experimental methods. Collectively, quarTeT is an efficient toolkit for studies of large-scale T2T genomes and can be accessed at http://www.atcgn.com:8080/quarTeT/home.html without registration.

The composition dynamics of transposable elements in human blastocysts.

Transposable elements (TEs) are mobile DNA sequences that can replicate themselves and play significant roles in embryo development and chromosomal structure remodeling. In this study, we investigated the variation of TEs in blastocysts with different parental genetic backgrounds. We analyzed the proportions of 1137 TEs subfamilies from six classes at the DNA level using Bowtie2 and PopoolationTE2 in 196 blastocysts with abnormal parental chromosomal diseases. Our findings revealed that the parental karyotype was the dominant factor influencing TEs frequencies. Out of the 1116 subfamilies, different frequencies were observed in blastocysts with varying parental karyotypes. The development stage of blastocysts was the second most crucial factor influencing TEs proportions. A total of 614 subfamilies exhibited different proportions at distinct blastocyst stages. Notably, subfamily members belonging to the Alu family showed a high proportion at stage 6, while those from the LINE class exhibited a high proportion at stage 3 and a low proportion at stage 6. Moreover, the proportions of some TEs subfamilies also varied depending on blastocyst karyotype, inner cell mass status, and outer trophectoderm status. We found that 48 subfamilies displayed different proportions between balanced and unbalanced blastocysts. Additionally, 19 subfamilies demonstrated varying proportions among different inner cell mass scores, and 43 subfamilies exhibited different proportions among outer trophectoderm scores. This study suggests that the composition of TEs subfamilies may be influenced by various factors and undergoes dynamic modulation during embryo development.

Optical genome mapping analysis of a Chinese pedigree with a rare chromosome 17 paracentric inversion insertion

To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17. A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women's Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree. Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal. The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.

Large-scale phenogenomic analysis of human cancers uncovers frequent alterations affecting SMC5/6 complex components in breast cancer.

Cancer cells often experience large-scale alterations in genome architecture because of DNA damage and replication stress. Whether mutations in core regulators of chromosome structure can also lead to cancer-promoting loss in genome stability is not fully understood. To address this question, we conducted a systematic analysis of mutations affecting a global regulator of chromosome biology -the SMC5/6 complex- in cancer genomics cohorts. Analysis of 64959 cancer samples spanning 144 tissue types and 199 different cancer genome studies revealed that the SMC5/6 complex is frequently altered in breast cancer patients. Patient-derived mutations targeting this complex associate with strong phenotypic outcomes such as loss of ploidy control and reduced overall survival. Remarkably, the phenotypic impact of several patient mutations can be observed in a heterozygous context, hence providing an explanation for a prominent role of SMC5/6 mutations in breast cancer pathogenesis. Overall, our findings suggest that genes encoding global effectors of chromosome architecture can act as key contributors to cancer development in humans.