Chromosomal Variation Research Articles

Unraveling the mysteries of early embryonic arrest: genetic factors and molecular mechanisms.

Early embryonic arrest (EEA) is a critical impediment in assisted reproductive technology (ART), affecting 40% of infertile patients by halting the development of early embryos from the zygote to blastocyst stage, resulting in a lack of viable embryos for successful pregnancy. Despite its prevalence, the molecular mechanism underlying EEA remains elusive. This review synthesizes the latest research on the genetic and molecular factors contributing to EEA, with a focus on maternal, paternal, and embryonic factors. Maternal factors such as irregularities in follicular development and endometrial environment, along with mutations in genes like NLRP5, PADI6, KPNA7, IGF2, and TUBB8, have been implicated in EEA. Specifically, PATL2 mutations are hypothesized to disrupt the maternal-zygotic transition, impairing embryo development. Paternal contributions to EEA are linked to chromosomal variations, epigenetic modifications, and mutations in genes such as CFAP69, ACTL7A, and M1AP, which interfere with sperm development and lead to infertility. Aneuploidy may disrupt spindle assembly checkpoints and pathways including Wnt, MAPK, and Hippo signaling, thereby contributing to EEA. Additionally, key genes involved in embryonic genome activation-such as ZSCAN4, DUXB, DUXA, NANOGNB, DPPA4, GATA6, ARGFX, RBP7, and KLF5-alongside functional disruptions in epigenetic modifications, mitochondrial DNA, and small non-coding RNAs, play critical roles in the onset of EEA. This review provides a comprehensive understanding of the genetic and molecular underpinnings of EEA, offering a theoretical foundation for the diagnosis and potential therapeutic strategies aimed at improving pregnancy outcomes.

Chromosome-level genome assembly of the morabine grasshopper Vandiemenella viatica19

Morabine grasshoppers in the Vandiemenella viatica species group, which show karyotype diversity, have been studied for their ecological distribution and speciation in relation to their genetic and chromosomal diversity. They are good models for studying sex chromosome evolution as “old” and newly emerged sex chromosomes co-exist within the group. Here we present a reference genome for the viatica19 chromosomal race, that possesses the ancestral karyotype within the group. Using PacBio HiFi and Hi-C sequencing, we generated a chromosome-level assembly of 4.09 Gb in span, scaffold N50 of 429 Mb, and complete BUSCO score of 98.1%, containing 10 pseudo-chromosomes. We provide Illumina datasets of males and females, used to identify the X chromosome. The assembly contains 19,034 predicted protein-coding genes, and a total of 75.21% of repetitive DNA sequences. By leveraging HiFi reads, we mapped the genome-wide distribution of methylated bases (5mC and 6 mA). This comprehensive assembly offers a robust reference for morabine grasshoppers and supports further research into speciation and sex chromosome diversification within the group and its related species.

Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death

BackgroundNeuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective.Materials and MethodsThe Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors.ResultUsing scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB.ConclusionThe results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

Genome Sequencing of Lentinula edodes Revealed a Genomic Variant Block Associated with a Thermo-Tolerant Trait in Fruit Body Formation.

The formation of multicellular fruiting bodies in basidiomycete mushrooms is a crucial developmental process for sexual reproduction and subsequent spore development. Temperature is one of the most critical factors influencing the phase transition for mushroom reproduction. During the domestication of mushrooms, traits related to fruiting bodies have significantly impacted agricultural adaptation and human preferences. Recent research has demonstrated that chromosomal variations, such as structural variants (SVs) and variant blocks (VBs), play crucial roles in agronomic traits and evolutionary processes. However, the lack of high-quality genomic information and important trait data have hindered comprehensive identification and characterization in Lentinula edodes breeding processes. In this study, the genomes of two monokaryotic L. edodes strains, characterized by thermo-tolerance and thermo-sensitivity during fruiting body formation, were reassembled at the chromosomal level. Comparative genomic studies of four thermo-tolerant and thermo-sensitive monokaryotic L. edodes strains identified a 0.56 Mbp variant block on chromosome 9. Genes associated with DNA repair or cellular response to DNA damage stimulus were enriched in this variant block. Finally, we developed eight CAPS markers from the variant block to discriminate the thermo-tolerant traits in L. edodes cultivars. Our findings show that the identified variant block is highly correlated with the thermo-tolerant trait for fruiting body formation and that alleles present in this block may have been artificially selected during L. edodes domestication.

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

BackgroundThe 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.MethodsA 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.ResultsSixteen 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).ConclusionThe 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.

Age-dependent genetic architectures of chicken body weight explored by multidimensional GWAS and molQTL analyses

Chicken body weight (BW) is a critical trait in breeding. Although genetic variants associated with BW have been investigated by genome-wide association studies (GWAS), the contributions of causal variants and their molecular mechanisms remain largely unclear in chickens. In this study, we construct a comprehensive genetic atlas of chicken BW by integrative analysis of 30 age points and 5 quantitative trait loci (QTL) across 27 tissues. We find that chicken growth is a cumulative non-linear process, which can be divided into three distinct stages. Our GWAS analysis reveals that BW-related genetic variations show ordered patterns in these three stages. Genetic variations in chromosome 1 may regulate the overall growth process, likely by modulating the hypothalamus-specific expression of SLC25A30 and retina-specific expression of NEK3. Moreover, genetic variations in chromosome 4 and chromosome 27 may play dominant roles in regulating BW during Stage Ⅱ (8–22 weeks) and Stage Ⅲ (23–72 weeks), respectively. In summary, our study presents a comprehensive genetic atlas regulating developmental stage-specific changes in chicken BW, thus providing important resources for genomic selection in breeding programs.

Genetic Aspects Of Autism Spectrum Disorder

Autism spectrum disorder is a clinically and etiologically heterogeneous group, affecting 1 in 59 children. The etiopathogenesis of these, basically, neurodevelopment disorders, has been the subject of research by numerous researchers for more than two decades, and involves complex genetic, environmental, and epigenetic mechanisms. Hundreds of genes have been identified that contribute to serious deficits in communication, social relations and patient behavior. So the main objective of the paper is to explain the way in which genetic modifiers and epigenetic changes have a key role in modulating the phenotypic spectrum of patients with autism spectrum disorder. The systematic review of literature is based on a review of the available scientific papers. Following PRISMA’s instructions, a systematic review of published papers in the period from 2016 to 2024 was performed. Our study included literature published in the MEDLINE/PubMed database in which the following keywords were used during the search: “autismspectrum disorder”, “pervasive developmental disorder”, “risk factors”, “genetics”, “phenotypic spectrumof ASD”, “genes”, “epigenetic mechanisms”. Тhe obtained results show that the genetic factor increases the risk for development of autism spectrum disorder. More genes have been identified that are involved in the development of autism spectrum disorder, such as: ADNP, ANK2, CHD2, CNTN4, DSCAM, etc. In addition to genetic variants, there is also evidence of de novo gene variants. At the same time, chromosomal deletions or duplications were found in patients, such as the following: 15q11.2, BP1-BP2, 16p11.2 and 15q13.3. Copy number variations are submicroscopic, structural variants in chromosomes that include duplications, deletions, translocations, and inversions, sometimes stretching several kilo bases. Many genes may be affected with these changes, but not all are necessarily drivers of disease. Epigenetic mechanisms, DNA methylation and chemical histone modification are mechanisms that affect gene expression without changing the primary structure of genes. Genetic research so far has enabled us to consider autism spectrum disorder from a different angle, and understand its etiopathogenesis as a complex interaction between genes and environmental factors as a predisposition for its occurrence

Genetics of female and male infertility.

Infertility is defined as the inability to conceive within one year of unprotected intercourse, and the causes are equally distributed between both sexes. Genetics play a crucial role in couple infertility and respective diagnostic testing should follow available guidelines. Appropriate tiered genetic analyses require comprehensive physical examination of both partners in an infertile couple. A wide range of chromosomal and monogenic variants can be the underlying genetic cause of infertility in both women and men. Accurate clinical phenotyping, together with identification of the genetic origin, helps to recommend the proper treatment and to counsel couples on the success rates and potential risks for offspring.

Characterization of 19 novel gene mutation sites associated with autosome-dominant polycystic kidney disease

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

HLA Alleles Associate with Insulin Autoimmune Syndrome.

In recent years, there have been hundreds of reports on insulin autoimmune syndrome (IAS) globally; however, fewer than a hundred patients have undergone genetic testing. Our objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302.

Innovative all-in-one exome sequencing strategy for diagnostic genetic testing in male infertility: Validation and 10-month experience.

Current guidelines indicate that patients with extreme oligozoospermia or azoospermia should be tested for chromosomal imbalances, azoospermia factor (AZF) deletions and/or CFTR variants. For other sperm abnormalities, no genetic diagnostics are recommended. To determine whether exome sequencing (ES) with combined copy number variant (CNV) and single nucleotide variant (SNV) analysis is a reliable first-tier method to replace current methods (validation study), and to evaluate the diagnostic yield after 10 months of implementation (evaluation study). In the validation study, ES was performed on DNA of patients already diagnosed with AZF deletions (n=17), (non-)mosaic sex chromosomal aneuploidies or structural chromosomal anomalies (n=37), CFTR variants (n=26), or variants in known infertility genes (n=4), and 90 controls. The data were analyzed using our standard diagnostic pipeline, with a bioinformatic filter for 130 male infertility genes. In the evaluation study, results of 292 clinical exomes were included. All previously reported variants in the validation cohort, including clinically relevant Y-chromosomal microdeletions, were correctly identified and reliably detected. In the evaluation study, we identified one or more clinically relevant genetic anomalies in 67 of 292 of all cases (22.9%): these included aberrations that could have been detected with current methods in 30 of 67 patients (10.2% of total), (possible) (mono)genetic causes in the male infertility gene panel in 28 of 67 patients (9.6%), and carriership of cystic fibrosis in nine of 67 patients (3.1%). ES is a reliable first-tier method to detect the most common genetic causes of male infertility and, as additional genetic causes can be detected, in our evaluation cohort the diagnostic yield almost doubled (10.2%-19.8%, excluding CF carriers). A genetic diagnosis provides answers on the cause of infertility and helps the professionals in the counseling for treatment, possible co-morbidities and risk for offspring and/or family members. Karyotyping will still remain necessary for detecting balanced translocations or low-grade chromosomal mosaicism.

PmrB Y358N, E123D amino acid substitutions are not associated with colistin resistance but with phylogeny in Escherichia coli.

Colistin is a critical last-resort treatment for extensively drug-resistant Gram-negative infections in humans. Therefore, accurate identification of the genetic mechanisms of resistance to this antimicrobial is crucial to effectively monitor and mitigate the spread of resistance. Examining over 16,000 whole-genome sequenced Escherichia coli isolates, this study identifies that PmrB E123D and Y358N amino acid substitutions previously associated with colistin resistance in E. coli are strongly associated with phylogroup and are alone not sufficient to confer a colistin-resistant phenotype. This is a critical clarification, as both substitutions are identified as putative mechanisms of colistin resistance in many publications and a common bioinformatic tool. Given the potential spurious nature of initial associations of these substitutions with colistin resistance, this study's findings emphasize the importance of appropriate experimental design and consideration of relevant biological factors such as phylogroup when ascribing causal mechanisms of resistance to chromosomal variations.

Research Priorities of Individuals and Families with Sex Chromosome Aneuploidies.

Sex chromosome aneuploidies (SCAs) are chromosomal variations that result from an atypical number of X and/or Y chromosomes. Combined, SCAs affect ~1/400 live births, including individuals with Klinefelter syndrome (47,XXY), Turner syndrome (45,X and variants), Double Y syndrome (47,XYY), Trisomy X (47,XXX), and rarer tetrasomies and pentasomies. Individuals with SCAs experience a wide variety of physical health, mental health, and healthcare experiences that differ from the standard population. To understand the priorities of the SCA community we surveyed participants in two large SCA registries, the Inspiring New Science in Guiding Healthcare in Turner Syndrome (INSIGHTS) Registry and the Generating Advancements in Longitudinal Analysis in X and Y Variations (GALAXY) Registry. 303/629 (48.1% response rate) individuals from 13 sites across the United States responded to the survey, including 251 caregivers and 52 self-advocates, with a range of ages from 3 weeks to 73 years old and represented SCAs including Turner syndrome, XXX, XXY, XYY, XXYY, and combined rare tetrasomies and pentasomies. Results demonstrate the priorities for physical health and emotional/behavioral health identified by the SCA community, as well as preferred types of research. All SCA subtypes indicated intervention studies as the top priority, emphasizing the need for researchers to focus on clinical treatments in response to priorities of the SCA community.

Genomic insights into prenatal diagnosis of congenital heart defects: value of CNV-seq and WES in clinical practice.

This study aimed to assess the efficiency of CNV-seq and WES in detecting genetic cause of congenital heart disease (CHDs) in prenatal diagnoses and to compare CNV detection rate between isolated and non-isolated CHD cases. We conducted a retrospective study of 118 Chinese fetuses diagnosed with CHD by prenatal ultrasound. Participants underwent CNV-seq and, if necessary, WES to detect chromosomal and single nucleotide variations. The overall detection rate for pathogenic or likely pathogenic chromosomal abnormalities was 16.9%, including 7.6% aneuploidies and 9.3% pathogenic/likely pathogenic copy number variations (CNVs), predominantly 22q11.2 deletion syndrome (54.4%). The sensitivity and specificity of CNV-Seq for detecting P/Lp CNVs were 95% and 100%, respectively. CNV-Seq offered a 6.7% improvement in detecting chromosomal abnormalities over karyotyping. WES further identified significant single nucleotide and small indel variations contributing to CHD in genes such as TMEM67, PLD1, ANKRD11, and PNKP, enhancing diagnostic yield by 14.8% in cases negative for CNVs. Non-isolated CHD cases exhibited higher rates of detectable chromosomal abnormalities compared to isolated cases (32.4% vs. 9.9%, p = 0.005), underlining the genetic complexity of these conditions. The combined use of CNV-seq and WES provides a comprehensive approach to prenatal genetic testing for CHDs, unveiling significant genetic cause that could impact clinical management and parental decision-making. This study supports the integration of these advanced genomic technologies in routine prenatal diagnostics to increase detection diagnostic yields of causal genetic variants associated with CHDs.

Genetic analysis of a child with mos 46,X,psu idic(X)(q21.3)[40]/45,X[3]

To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia. A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively. The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46,X,psu idic(X)(q21.3)[40]/mos 45,X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45,X karyotype and the location of the breaking point. 46,X,psu idic(X)(q21.3)/45,X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.

Integrating Genetic and Cytogenetic Data: A Diversity Study of Astyanax and Psalidodon (Characidae) Species from the Paraná River Basin.

Astyanax is one of the most specious fish groups in the Neotropical region, with many cryptic species, which represents a challenge for correct identification through traditional taxonomic methods. Psalidodon is a recently resurrected genus group of species previously belonging to Astyanax, specifically those with extensive chromosomal variation of the A. scabripinnis and fasciatus complexes. In the present study, the mitochondrial genes cytochrome c oxidase subunit 1 (COI), mitochondrial ATP synthase 6 and 8 (ATPase 6/8), and NADH dehydrogenase subunit 2 (ND2) were used in conjunction with chromosomal data to characterize molecularly and cytogenetically populations of Astyanax and Psalidodon from rivers and streams of the Ivaí River Basin (Paraná Basin). The results demonstrated the effectiveness of the integrative use of molecular and cytogenetic techniques, with the confirmation of at least three species for the sampled sites: A. lacustris, P. paranae, and P. fasciatus, which showed inter- and intrapopulation karyotype variations. In addition, extensive haplotypic variation can be observed for these species within the Ivaí River Basin and throughout the Paraná River Basin. The data demonstrate a hidden diversity among the species analyzed, enrich the ichthyofaunistic knowledge of small rivers and streams, and contribute to future conservation projects in these areas.

Distribution and molecular analysis of Subtilase cytotoxin gene (subAB) variants in Shiga toxin-producing Escherichia coli (STEC) isolated from different sources in Iran.

Subtilase exhibits strong cytotoxicity that was first described in O113:H21 strain in Australia as a plasmid- encoded cytotoxin (subAB1). Subsequently, chromosomal variants including subAB2-1, subAB2-2, and subAB2-3 were described. We aimed to investigate the presence of subAB genes in a collection of Shiga toxin-producing Escherichia coli (STEC) strains (n=101) isolated from different sources in Iran. A collection of 101 archived STEC strains isolated from cattle (n=50), goats (n=25), sheep (n=15), wild captive animals (n=8: persian fallow deer, n=3; caspian pony, n=1; Macaca mulatta, n=4), and humans (n=3) during 2007-2016 were analyzed for the detection of different genes encoding the Subtilase variants, plasmidic and chromosomal virulence genes, phylogroups and serogroups. Overall, 57 isolates (56.4%) carried at least one variant of subAB. Most strains from small ruminants including 93% of sheep and 96% of caprine isolates carried at least one chromosomally encoded variant (subAB-2-1 and/or subAb2-2). In contrast, 12 cattle isolates (24%) only harbored the plasmid encoded variant (subAB1). STEC strains from other sources, including deer, pony and humans were positive for subAB-2-1 and/or subAb2-2. Our results reveal the presence of potentially pathogenic genotypes among locus of enterocyte effacement (LEE)-negative isolates, and some host specificity related to Subtilase variants and other virulence markers that may aid in source tracking of STEC during outbreak investigations.

Metastatic Leiomyoma With Malignant Transformation Harboring RAB2A-PLAG1 Fusion-A Case Report and Review With Molecular Analysis.

Metastasizing leiomyoma is a rare condition characterized by the development of benign-appearing smooth muscle neoplasms at extrauterine sites in patients with a history of uterine leiomyoma. These lesions occur most commonly in the lung, with the abdominopelvic and mediastinal lymph nodes being other reported sites. Malignant transformation of metastasizing leiomyoma is extremely rare, with only a few cases described in the literature. We describe a case of metastasizing leiomyoma with malignant transformation in a middle-aged Asian lady, who developed pulmonary metastatic foci 12 years after surgical excision of the original uterine leiomyomata. Molecular analysis showed a common RAB2A-PLAG1 fusion gene and identical single nucleotide variants in both tumor foci, with significantly more pronounced segmental chromosomal copy number variations in one focus showing high-grade features. A comprehensive review of the literature lends support to the hypothesis that the original leiomyomata and the metastatic foci are clonally related, with high-grade features being associated with more complex genomic signatures.

Underground speciation: Unraveling the systematics and evolution of the highly diverse tuco-tucos (genus Ctenomys) with genomic data

Subterranean rodents of the genus Ctenomys (tuco-tucos) are endemic to South America and have experienced relatively recent radiation. There are about 67 recognized species that originated in approximately 1–2 MY. They stand out for their species richness, extraordinary chromosomal diversity, and wide range of habitat they occupy in the continent. Phylogenetic relationships among species of tuco-tucos have been challenging to resolve. Groups of closely-related species have been suggested, but their relationships must be resolved. This study estimates the phylogeny of the genus using massive sequencing, generating thousands of independent molecular markers obtained by RADseq, with a taxonomic sampling that includes 66% of the recognized species. The sequences obtained were mapped against the C. sociabilis genome, recovering up to 1,215 widely shared RAD loci with more than 19,000 polymorphic sites. Our new phylogenetic hypothesis corroborated the species groups previously proposed with cytochrome b gene sequences and provided a much greater resolution of the relationships among species groups. The frater group is sister to all other tuco-tucos, whereas some of the earlierliest proposals placed the sociabilis group as sister to all other tuco-tucos. Ctenomys leucodon, previously proposed as an independent lineage, is associated with the frater group with moderate statistical support. The magellanicus and mendocinus are sister groups in a major clade formed by the boliviensis, talarum, tucumanus, torquatus, and opimus groups. Ctenomys viperinus, included in the phylogeny for the first time, belongs to the tucumanus group. This multi-locus phylogenetic hypothesis provides insights into the historical biogeography of understanding this highly diverse genus.

Evolution and regulation of animal sex chromosomes.

Animal sex chromosomes typically carry the upstream sex-determining gene that triggers testis or ovary development and, in some species, are regulated by global dosage compensation in response to functional decay of the Y chromosome. Despite the importance of these pathways, they exhibit striking differences across species, raising fundamental questions regarding the mechanisms underlying their evolutionary turnover. Recent studies of non-model organisms, including insects, reptiles and teleosts, have yielded a broad view of the diversity of sex chromosomes that challenges established theories. Moreover, continued studies in model organisms with recently developed technologies have characterized the dynamics of sex determination and dosage compensation in three-dimensional nuclear space and at single-cell resolution. Here, we synthesize recent insights into sex chromosomes from a variety of species to review their evolutionary dynamics with respect to the canonical model, as well as their diverse mechanisms of regulation.