Prenatal diagnosis of fetuses with 15q11.2 BP1-BP2 microdeletion in the Chinese population: a seven-year single-center retrospective study.

BACKGROUND: The 15q11.2 BP1-BP2 microdeletion syndrome is associated with developmental delays, language impairments, neurobehavioral disorders, and psychiatric complications. The aim of the present study was to provide prenatal and postnatal clinical data for 16 additional fetuses diagnosed with the 15q11.2 BP1-BP2 microdeletion syndrome in the Chinese population. METHODS: A total of 5,789 pregnancy women that underwent amniocentesis were enrolled in the present study. Both karyotype analysis and chromosomal microarray analysis (CMA) were conducted on these subjects to detect chromosomal abnormalities and copy number variants (CNVs). Whole exome sequencing (WES) was performed to investigate sequence variants in subjects with clinical abnormalities after birth. RESULTS: Sixteen fetuses with 15q11.2 BP1-BP2 microdeletion were identified in the present study, with a detection rate of 0.28% (16/5,789). The 15q11.2 BP1-BP2 microdeletion fragments ranged from 311.8 kb to 849.7 kb, encompassing the NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes. The follow-up results regarding pregnancy outcomes showed that five cases opted for pregnancy termination, while the remaining cases continued with their pregnancies. Subsequent postnatal follow-up indicated that only one case with the 15q11.2 BP1-BP2 microdeletion displayed neurodevelopmental disorders, demonstrating an incomplete penetrance rate of 9.09% (1/11). CONCLUSION: The majority of fetuses with the 15q11.2 microdeletion exhibit typical features during early childhood, indicating a low penetrance and mild impact. Nonetheless, pregnancies involving fetuses with the 15q11.2 microdeletion require thorough prenatal counseling. Additionally, enhanced supervision and extended postnatal monitoring are warranted for those who choose to proceed with their pregnancies.

The genome sequence of the Atlantic cod, Gadus morhua (Linnaeus, 1758).

We present a genome assembly from an individual male Gadus morhua (the Atlantic cod; Chordata; Actinopteri; Gadiformes; Gadidae). The genome sequence is 669.9 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules. Gene annotation of this assembly on Ensembl identified 23,515 protein coding genes.

The genome sequence of black poplar, Populus nigra subsp. betulifolia L., 1753 (Salicaceae).

We present a genome assembly from an individual Populus nigra subsp. betulifola (black poplar; Tracheophyta; Malpighiales; Salicaceae). The genome sequence is 413.2 megabases in span. Most of the assembly (99.73%) is scaffolded into 19 chromosomal pseudomolecules. Mitochondrial and plastid genomes were also assembled. Three mitochondrial assemblies have lengths of 281.85, 335.57 and 186.15 kilobases, and the plastid genome has a length of 156.37 kilobases.

The genome sequence of the Scarlet Tiger moth, Callimorpha dominula (Linnaeus, 1758).

We present a genome assembly from an individual male Callimorpha dominula (the Scarlet Tiger moth; Arthropoda; Insecta; Lepidoptera; Erebidae). The genome sequence is 658.1 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.45 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,234 protein coding genes.

The genome sequence of an ichneumonid wasp, Exephanes ischioxanthus (Gravenhorst, 1829).

We present a genome assembly from an individual male Exephanes ischioxanthus (an ichneumonid wasp; Arthropoda; Insecta; Hymenoptera; Ichneumonidae). The genome sequence is 284.0 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 19.43 kilobases in length.

The genome sequence of the European pine marten, Martes martes (Linnaeus, 1758).

We present a genome assembly from an individual male Martes martes (the European pine marten; Chordata; Mammalia; Carnivora; Mustelidae). The genome sequence is 2,484.6 megabases in span. Most of the assembly is scaffolded into 20 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.57 kilobases in length.

The genome sequence of the Green Silver-lines, Pseudoips prasinana (Linnaeus, 1758).

We present a genome assembly from an individual female Pseudoips prasinana (the Green Silver-lines; Arthropoda; Insecta; Lepidoptera; Nolidae). The genome sequence is 1,125.7 megabases in span. Most of the assembly is scaffolded into 33 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.23 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,065 protein coding genes.

The genome sequence of the marbled rockcod, Notothenia rossii Richardson, 1844.

We present a genome assembly from an individual Notothenia rossii (the marbled rockcod; Chordata; Actinopterygii; Perciformes; Nototheniidae). The genome sequence is 1,042.9 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 21.68 kilobases in length. Gene annotation of this assembly on Ensembl identified 24,432 protein coding genes.

The genome sequence of the Mauritius kestrel, Falco punctatus (Temminck, 1821).

We present a genome assembly from an individual male Falco punctatus (the Mauritius kestrel; Chordata; Aves; Falconiformes; Falconidae). The genome sequence is 1,279.3 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 17.34 kilobases in length.

The genome sequence of a segmented worm, Terebella lapidaria Linnaeus, 1767.

We present a genome assembly from an individual Terebella lapidaria (segmented worm; Annelida; Polychaeta; Terebellida; Terebellidae). The genome sequence spans 765.20 megabases. Most of the assembly is scaffolded into 16 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.97 kilobases in length.

The genome sequence of the Mournful Wasp, Pemphredon lugubris (Fabricius, 1793).

We present a genome assembly from an individual male Pemphredon lugubris (the Mournful Wasp; Arthropoda; Insecta; Hymenoptera; Crabronidae). The genome sequence is 328.1 megabases in span. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.88 kilobases in length. Gene annotation of this assembly on Ensembl identified 10,335 protein coding genes.

Exploring the human genomic landscape: patterns of common homozygosity regions in a large middle eastern cohort.

Regions of Homozygosity (ROH) typically reflect normal demographic history of a human population, but may also relate to cryptic consanguinity, and, additionally, have been associated with specific medical conditions. The objective of this study was to investigate the location, size, and prevalence of common ROH segments in a Middle Eastern cohort. This retrospective study included 13 483 samples collected from all Chromosomal Microarray analyses (CMA) performed using Single Nucleotide Polymorphism (SNP) arrays at the genetic clinical laboratory of Rabin Medical Center between 2017-2023 (primary data set). An additional replication cohort including 100 842 samples from another SNP array platform, obtained from Maccabi Health Organization, was analyzed. Common ROH locations were defined as those ROH locations involving 1% or more of the samples. A total of 66 710 ROH segments, involving 13 035 samples (96.7%) were identified in the primary data set. Of the 4069 cytogenetic ROH locations, 68 were identified as common. The prevalence of non-common ROH was relatively high in affected individuals, and for acrocentric chromosomes, chromosomes associated with common trisomies, and non-imprinted chromosomes. In addition, differences in common ROH locations were observed between the primary and the replication cohorts. Our findings highlight the need for population-specific guidelines in determining ROH reporting cutoffs, considering factors such as population-specific prevalence and testing platform differences. Future research with larger, varied cohorts is essential to advance understanding of ROH's associations with medical conditions and to improve clinical practices accordingly.

Exploring the link between chromosomal polymorphisms and reproductive abnormalities.

OBJECTIVE: This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. METHODS: We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. RESULTS: Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. CONCLUSION: Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

The genome sequence of the particolored bat, Vespertilio murinus Linnaeus, 1758.

We present a genome assembly from an individual male Vespertilio murinus (the particolored bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 1,925.6 megabases in span. Most of the assembly is scaffolded into 20 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.96 kilobases in length.

The genome sequence of the Elephant Hawk-moth, Deilephila elpenor (Linnaeus, 1758).

We present a genome assembly from an individual female Deilephila elpenor (the Elephant Hawk-moth; Arthropoda; Insecta; Lepidoptera; Sphingidae). The genome sequence is 414.1 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.37 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,748 protein coding genes.

The genome sequence of Rhynchonycteris naso, Peters, 1867 (Chiroptera, Emballonuridae, Rhynchonycteris).

We present a reference genome assembly from an individual male Rhynchonycteris naso (Chordata; Mammalia; Chiroptera; Emballonuridae). The genome sequence is 2.46 Gb in span. The majority of the assembly is scaffolded into 22 chromosomal pseudomolecules, with the Y sex chromosome assembled.

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10's multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment.

Low-pass whole genome sequencing of circulating tumor cells to evaluate chromosomal instability in triple-negative breast cancer.

Chromosomal Instability (CIN) is a common and evolving feature in breast cancer. Large-scale Transitions (LSTs), defined as chromosomal breakages leading to gains or losses of at least 10 Mb, have recently emerged as a metric of CIN due to their standardized definition across platforms. Herein, we report the feasibility of using low-pass Whole Genome Sequencing to assess LSTs, copy number alterations (CNAs) and their relationship in individual circulating tumor cells (CTCs) of triple-negative breast cancer (TNBC) patients. Initial assessment of LSTs in breast cancer cell lines consistently showed wide-ranging values (median 22, range 4-33, mean 21), indicating heterogeneous CIN. Subsequent analysis of CTCs revealed LST values (median 3, range 0-18, mean 5), particularly low during treatment, suggesting temporal changes in CIN levels. CNAs averaged 30 (range 5-49), with loss being predominant. As expected, CTCs with higher LSTs values exhibited increased CNAs. A CNA-based classifier of individual patient-derived CTCs, developed using machine learning, identified genes associated with both DNA proliferation and repair, such as RB1, MYC, and EXO1, as significant predictors of CIN. The model demonstrated a high predictive accuracy with an Area Under the Curve (AUC) of 0.89. Overall, these findings suggest that sequencing CTCs holds the potential to facilitate CIN evaluation and provide insights into its dynamic nature over time, with potential implications for monitoring TNBC progression through iterative assessments.

Chromosomal instability: a key driver in glioma pathogenesis and progression.

Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN's role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN's impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN's role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN's effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.

The genome sequence of a drosophilid fruit fly, Drosophila limbata von Roser 1840.

We present a genome assembly from an individual male Drosophila limbata (drosophilid fruit fly; Arthropoda; Insecta; Diptera; Drosophilidae). The genome sequence is 233.5 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.09 kilobases in length.