Cytogenetic Research Articles

The complete sequence and comparative analysis of ape sex chromosomes

Apes possess two sex chromosomes—the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements—owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.

A new Senecio (Asteraceae) from the Anjaneri Hills of Nashik, India

A new species of Senecio (Asteraceae, Senecioneae), Senecio anjanericus is described and illustrated from the Anjaneri Hills of Nashik district, Maharashtra, India, based on morphological and cytogenetical studies. The species resembles Senecio bombayensis, but differs from it in small size of the ligules, presence of conspicuous foliose supplementary bracts and dense indumentum on stem. The somatic chromosome number was observed to be 2n = 2x = 20, with all the chromosomes exhibiting median region centromeres. A detailed morphological description, illustration and karyotypic features of the new species are provided.

Use of peptide nucleic acid probe to determine telomere dynamics in improving chromosome analysis in genetic toxicology studies

Genetic toxicology, strategically located at the intersection of genetics and toxicology, aims to demystify the complex interplay between exogenous agents and our genetic blueprint. Telomeres, the protective termini of chromosomes, play instrumental roles in cellular longevity and genetic stability. Traditionally karyotyping and fluorescence in situ hybridisation (FISH), have been indispensable tools for chromosomal analysis following exposure to genotoxic agents. However, their scope in discerning nuanced molecular dynamics is limited. Peptide Nucleic Acids (PNAs) are synthetic entities that embody characteristics of both proteins and nucleic acids and have emerged as potential game-changers. This perspective report comprehensively examines the vast potential of PNAs in genetic toxicology, with a specific emphasis on telomere research. PNAs' superior resolution and precision make them a favourable choice for genetic toxicological assessments. The integration of PNAs in contemporary analytical workflows heralds a promising evolution in genetic toxicology, potentially revolutionizing diagnostics, prognostics, and therapeutic avenues. In this timely review, we attempted to assess the limitations of current PNA-FISH methodology and recommend refinements.

Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential.

Human induced pluripotent stem cell (hiPSC) technology is a valuable tool for generating patient-specific stem cells, facilitating disease modeling, and investigating disease mechanisms. However, iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics. To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles (EVs) influence anomalous cell junction and differentiation potential. We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation. Chromosomal karyotype analysis, flow cytometry, and immunofluorescent staining were utilized for hiPSC identification. Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential. Additionally, EVs were isolated from the supernatant, and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation. The generated hiPSCs, both with and without a MERTK mutation, exhibited normal karyotype and expressed pluripotency markers; however, hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential, as confirmed by transcriptomic and proteomic profiling. Furthermore, hiPSC-derived EVs were involved in various biological processes, including cell junction and differentiation. HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential. Furthermore, hiPSC-derived EVs played a regulatory role in various biological processes, including cell junction and differentiation.

Genome-wide identification and analysis of the cotton ALDH gene family

BackgroundAldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehyde molecules into the corresponding carboxylic acid, regulate the balance of aldehydes and protect plants from the poisoning caused by excessive accumulation of aldehydes; however, this gene family has rarely been studied in cotton.ResultsIn the present study, genome-wide identification was performed, and a total of 114 ALDH family members were found in three cotton species, Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii. The ALDH genes were divided into six subgroups by evolutionary analysis. ALDH genes in the same subgroup showed similar gene structures and conserved motifs, but some genes showed significant differences, which may result in functional differences. Chromosomal location analysis and selective pressure analysis revealed that the ALDH gene family had experienced many fragment duplication events. Cis-acting element analysis revealed that this gene family may be involved in the response to various biotic and abiotic stresses. The RT‒qPCR results showed that the expression levels of some members of this gene family were significantly increased under salt stress conditions. Gohir.A11G040800 and Gohir.D06G046200 were subjected to virus-induced gene silencing (VIGS) experiments, and the sensitivity of the silenced plants to salt stress was significantly greater than that of the negative control plants, suggesting that Gohir.A11G040800 and Gohir.D06G046200 may be involved in the response of cotton to salt stress.ConclusionsIn total, 114 ALDH genes were identified in three Gossypium species by a series of bioinformatics analysis. Gene silencing of the ALDH genes of G. hirsutum revealed that ALDH plays an important role in the response of cotton to salt stress.

Genetic etiology of agenesis of the corpus callosum: a retrospective single-center cohort analysis of 114 fetuses.

The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined.

Shared chromosome 21q loss in a mixed subtype renal cell carcinoma: composite or collision tumor?

Clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC) are the two most frequentlyencountered subtypes of renal cell carcinoma (RCC). Rarely, these two entities are identified intermingled within thesame mass and have been labeled either collision tumors juxtaposed by random chance or composite tumors thathave arisen from a common tumorigenic precursor cell. Regarding this distinction, authors have commonly reliedupon macroscopic, histologic, and clinicopathologic findings, which may be prone to subjectivity. Objectivemolecular evidence has been lacking. We present a renal tumor showing a mixed CCRCC and PRCC withcorroborating histologic, immunophenotypic, chromosomal microarray analysis (CMA), and next-generationsequencing (NGS) analysis for the respective tumor components, including classic findings of chromosome 3p lossand VHL mutation within the CCRCC component and gain of chromosomes 7 and 17 within the PRCC component.Of novel interest, CMA revealed a shared loss of chromosome 21q in both components with no other identifiableshared or overlapping mutations. This report adds unique evidence supporting the possibility of a true compositerenal cell carcinoma composed of two commonly recognized subtypes. This finding may help to inform earlymolecular pathogenetic mechanism of RCC tumorigenesis.

Interrelationships and Taxonomic Status of some Species of &lt;I&gt;Solanum nigrum&lt;/I&gt; Complex

Biosystematic studies have been carried out on some species of the Solanum nigrum complex, viz., diploid S. nigrum, S. nadiflorum, tetraploid S. nigrum, S. luteum and S. villosum. A comparison of fruit colour and chromosome number of the taxa divides them into two groups. Diploid S. nigrum and S. nodiflorum have shiny bluish black fruits and n = 12 chromosomes. In tetraploid S. nigrum the fruits are orange red while in S. luteum and S. villosum the fruits are yellow and the chromosome number in all the three taxa is n = 24. Meiosis was normal in all the species. The close relationship between diploid S. nigrum and S. nodiflorum, and among the species tetraploid S. nigrum, S. luteumand villosum has been confirmed by cytogenetical studies and statistical comparison of mean values of morphological characters.In the light of the foregoing studies a taxonomic revision of the species studied is suggested.

A new look at genetic variability in pomegranate: Landscape genetics and structural equation modeling (SEM)

Pomegranate (Punica granatum L.) is an important horticultural plant in Iran and has been a food source since ancient times. Despite several genetic diversity studies conducted on these taxa, there are no reports on the landscape genetics of these important plants in Iran, nor is there any information on the effects of environmental, spatial, and climatic variables on the genetic structure of pomegranate. Therefore, this study used genetics, structural equation modeling (SEM), and species distribution modeling (SDM) approaches to explore the above-mentioned objectives. We used both cytogenetic and molecular analyses (SSR and SCoT markers) of several pomegranate samples along with environmental, spatial, and climatic variables. The redundancy analysis (RDA) analysis showed a significant positive association between terminal chiasmata with the longitudinal distribution of the pomegranate accession, while total chiasma number and interstitial chiasmata have an association with the altitude. The spatial PCA analysis indicated the role played by both global and local spatial variables in the cytogenetic variability like the univalent and terminal chiasmata formation. The Mantel test indicates that the cytogenetic difference in pomegranate plants is not related to their geographical distance, while the Moran I test result shows that geographical regions with similar spatial conditions affect the cytogenetic structuring of pomegranate plants in a similar way. SEM methods showed a strong negative association between bivalent formation and the environmental variables, while they showed both positive and negative associations between some of the environmental variables and different kinds of chiasmata. The sPCA analysis of molecular data showed a significant global, and local, spatial structuring of the molecular data and the genetic cline formation within the pomegranate accessions studied. Similarly, the spatial PCA analysis of climate variables, precipitation, and temperature revealed a significant structuring of genetic diversity and the formation of genetic clines by these factors. RDA analysis identified some of the loci that are significantly associated with temperature and precipitation. Therefore, both geographical/ or spatial variables and climate factors contribute to the genetic structure of the pomegranate accessions studied. SEM models based on genetic data revealed a positive association between environmental and climate variables with genetic diversity parameters and SSR-SCoT molecular loci studied. Climate change is unlikely to hurt pomegranate growing areas due to the high genetic diversity of pomegranate plants and the diverse genetic lineages present in the country.

Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes.

Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by uncontrolled proliferation of myeloid precursor cells within bone marrow. Despite advances in understanding of its molecular underpinnings, AML remains a therapeutic challenge due to its high relapse rate and clonal evolution. In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented. Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse. Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.

Chromosomal aberration analysis: Novel noninvasive techniques for early-stage cancer screening

ObjectiveChromosome breakage is a catastrophic event that leads to the progressive development and progression of cancer. In order to analyze the changes of peripheral blood microenvironment of tumor patients, to explore the indicators of non-specific non-invasive tumor early screening. This paper presents a new idea of whether the gene sequence near the DNA damage break point is the gene sequence that controls the unrestricted growth of normal cells. MethodsThe chromosomal aberrations of peripheral blood lymphocytes were analysed in 60 healthy adult and 49 cancer patients before radiotherapy. ResultsThe detection rate of chromosomal aberrations was high in tumor patients, and “dicentric + translocations” of chromosomes were detected in 36 patients (73.47 %). The chi-square test showed statistically significant differences (P < 0.01), and chromosome adhesion and dissolution were observed. Conclusions“Dicentric + Translocation” chromosome can be used as a nonspecific early screening indicator for cancer. This is worthy of further study. This index can be used to determine the genetic basis of various cancers at the gene level to modify the base sequence and prevent the occurrence of cancer. It is worthy of further study, and it can provide a new method for gene therapy of tumors.

Chromosomal Variations and Clinical Features of Acute Lymphoblastic Leukemia in the North Indian Population: A Cross-Sectional Study.

The key prognostic markers in acute lymphoblastic leukemia (ALL) include age, leukocyte count upon diagnosis, immunophenotype, and chromosomal abnormalities. Furthermore, there was a correlation between cytogenetic anomalies and specific immunologic phenotypes of ALL, which in turn had varied outcomes. The objective of this study was to examine the occurrence of cytogenetic abnormalities in individuals diagnosed with acute lymphoblastic leukemia. The study employed a cross-sectional design to investigate genetic evaluation and clinical features in 147 ALL patients between March 2021 and August 2022. Demographic data (like age and sex), clinical manifestations, and hematological parameters were collected. Cytogenetic analysis (G-banding) was performed to identify chromosomal abnormalities. The mean±SD and analysis of variance (ANOVA) were usedtoassess associations and differences among variables usingSPSS Version 24 (IBM Corp., Armonk, NY, USA). The study shows male n=85 andfemale n=62 in ALL patients, with prevalent clinical manifestations: fever n=100 (68.03%), pallor n=123 (83.67%), and lymphadenopathy n=65 (44.22%).Thehematologicalparameters like hemoglobin (Hb) (6.14±2.5 g/dl),total leukocyte count (TLC)(1.7±1.05 cell/mm3), and platelet count (1.2±0.11 lac/mm3) show a significant variation (P<0.05) in patients aged 30-50 years.In addition,chromosomal abnormalities, particularly 46, XX, t(9;22), were prevalent, emphasizing the genetic heterogeneity of ALL. The study shows a male predominance with ALL, prevalent clinical manifestations, and significant hematological parameter variations in the 30-50 age group. Chromosomal abnormalities, notably 46, XX, t(9;22), underscore the genetic complexity of the disease, which necessitates tailored therapeutic interventions informed by genetic profiles.

Prenatal Screening and Diagnosis: Time for a Paradigm Shift.

Recent advances in genetics and imaging have ushered substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that health care providers caring for pregnant individuals should reexamine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 years were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screenings will fail to detect between 5 and 20% of Down syndrome, in most situations, noninvasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies and, therefore, in settings with adequately trained personnel and resources, should be used more frequently. This opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities. KEY POINTS: · Noninvasive prenatal testing with cell-free DNA should be available to all pregnant individuals.. · Chromosomal microarray should be available to all pregnant individuals undergoing amniocentesis.. · Patients >35 years with low-risk screening are not at "high risk" for chromosomal abnormalities..

Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging.

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.

Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth

BackgroundThe absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES).ResultsUsing SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions.ConclusionsHere we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Clinical Features and Treatment Outcome of Pediatric Acute Promyelocytic Leukemia in Combined Military Hospital, Dhaka

Background: Acute promyelocytic leukemia (APML) is a relatively rare blood disease in children that is highly curable with current treatment strategies. It is a distinct type of AML characterized by chromosomal translocations involving the retinoid acid receptor (RAR-A) gene on chromosome 17. It accounts for 20-25% of all AML cases. The aim of this study was to describe the diagnostic features of pediatric APL and the result with ATRA and ATO based protocol. Methods: It was a descriptive type of cross-sectional study with purposively selected 10 newly diagnosed APML patients treated in the Pediatric Oncology unit of the Department of Pediatrics in CMH Dhaka during the period of 2018 to 2022. Diagnosis of all patients were done by aspirating bone marrow morphology and cytogenetic t(15:17) or t(11:17) transcript. Informed written consent was taken from parents. Data were collected by semi-structured questionnaire and analyzed by Statistical Package for Social Sciences (SPSS version 25). Results: Among 10 respondents median age was 4.2 years with female predominant (60%). Most common clinical presentations at diagnosis were fever (100%), bleeding manifestations (100%), Hepatomegaly (90%) bony tenderness (90%), splenomegaly (70%), and lymphadenopathy (70%). Almost all the patients had low Hb &amp; low platelet count &amp; WBC were variable. Cytogenetic analysis revealed 90% had PML/RARA positive &amp; 30% had FLT3/ITD positive. All of these patients were treated with trans-retinoic acid (ATRA) based treatment, which led to 80% cases ATRA syndrome. Other common toxicities noticed febrile neutropenia (50%), severe headache (30%), hyperpigmented skin (10%), pseudotumor cerebri (10%) and others. There were 10% relapse cases, which later proceeded to relapse protocol and were in remission. The remaining 90% of patients were alive and in remission until the last day of follow-up. Conclusion: With ATRA-based treatment overall survival is good achieved remission and only 10% of patients developed relapse. Bangladesh Armed Forces Med J Vol 56 No (2) December 2023, pp 1-9

Microcephaly and Its Related Syndromes: Classification, Genetic, Clinical, and Rehabilitative Considerations

AbstractMicrocephaly, a form of cortical cortex malformation, results from abnormal cellular production and proliferation, identified when the occipital frontal head circumference (OFC) falls two or more standard deviations (SDs) below the expected average for age, gender, and population. Severity is classified based on SD: mild (OFC &lt; 2 SD) or severe (OFC &lt; 3 SD). While microcephaly can lead to developmental delay, intellectual disability, epilepsy, and cerebral palsy, not all cases exhibit these issues. Classified as primary/congenital or secondary/postnatal, microcephaly can stem from genetic or acquired factors in both types. Congenital microcephaly origins vary, while secondary microcephaly is characterized by normal OFC at birth, followed by a decrease within the first year, often associated with progressive cognitive and motor impairments. Primary hereditary microcephaly (MCPH), or microcephaly vera, is genetically diverse, with 28 related genes (MCPH1 to MCPH28) encoding proteins linked to centrosomes and progenitor cell mitosis in the brain ventricle's neuroepithelium. Defects in deoxyribonucleic acid (DNA) repair pathways (e.g., NBN, FANCA, ATR, ATM genes) can lead to microcephaly by impairing DNA repair. Enzyme deficiencies in metabolic pathways may also contribute, causing toxic metabolite accumulation or essential metabolite loss (microcephaly of metabolic origin). Acquired congenital microcephaly may result from ischemic or infectious processes, drugs, radiation, maternal diseases during pregnancy, with damage influenced by fetal genetics, environmental interactions, developmental stage, and exposure intensity/duration. Diagnostic workup includes electroencephalogram, ophthalmological, auditory, magnetic resonance imaging, metabolic, echocardiogram, and infection screening tests, alongside genetic evaluations like cytogenetic studies, fluorescence in situ hybridization, comparative genomic microarray-hybridization, single-nucleotide microarray-polymorphism, and exome sequencing. Symptomatic treatment is available, and genetic counseling is crucial for affected families.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study

ObjectiveTo determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction.Study designA total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored.ResultsThe karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development.ConclusionsThis study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Combined cytogenetic and molecular methods for taxonomic verification and description of Brassica populations deriving from different origins

Agriculture faces great challenges to overcome global warming and improve system sustainability, requiring access to novel genetic diversity. So far, wild populations and local landraces remain poorly explored. This is notably the case for the two diploid species, Brassica oleracea L. (CC, 2n=2x=18) and B. rapa L. (AA, 2n=2x=20). In order to explore the genetic diversity in both species, we have collected populations in their centre of origin, the Mediterranean basin, on a large contrasting climatic and soil gradient from northern Europe to southern sub-Saharan regions. In these areas, we also collected 14 populations belonging to five B. oleracea closely related species. Our objective was to ensure the absence of species misidentification at the seedling stage among the populations collected and to describe thereafter their origins. We combined flow cytometry, sequencing of a species-specific chloroplast genomic region, as well as cytogenetic analyses in case of unexpected results for taxonomic verification. Out of the 112 B. oleracea and 154 B. rapa populations collected, 103 and 146, respectively, presented a good germination rate and eighteen populations were misidentified. The most frequent mistake was the confusion of these diploid species with B. napus. Additionally for B. rapa, two autotetraploid populations were observed. Habitats of the collected and confirmed wild populations and landraces are described in this study. The unique plant material described here will serve to investigate the genomic regions involved in adaptation to climate and microbiota within the framework of the H2020 Prima project ‘BrasExplor’.

Genetic analysis and assisted reproductive guidance for two infertile patients with rare small supernumerary marker chromosomes

To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC). Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47,XY,del(16)(p10p12),+mar[65]/46,XY,del(16)(p10p12)[6]/48,XY,del(16)(p10p12),+2mar[3].ish mar(Tel 16p-,Tel 16q-,CEP 16-,WCP 16+). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47,XX,+mar[37]/46,XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5:g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.