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Purpose To assess the frequency and types of chromosomal abnormalities in 204 Ukrainian patients with non-obstructive azoospermia and oligozoospermia and 87 men with normozoospermia. Methods Cytogenetic studies were performed on peripheral blood lymphocyte samples of 164 men with oligozoospermia, 40 men with non-obstructive azoospermia and 87 men with normozoospermia attending infertility clinic. Results Chromosomal abnormalities were detected in 17 % of patients with sperm disorders: in 35 % of men with azoospermia and in 12.7 % of men with oligozoospermia. The frequency of chromosomal abnormalities in patients with sperm disorders was significantly higher, than in patients with normozoospermia ( P  = 0.0001). An increase in the incidence of chromosomal abnormalities with the decrease of sperm count was observed. Chromosomal abnormalities were detected in 1.1 % of patients with normozoospermia, 6.5 % of patients with mild oligozoospermia (sperm count 5–15 × 10 6 /ml), 18.4 % of patients with severe oligozoospermia (sperm count <5 × 10 6 /ml) and 35 % of patients with azoospermia. A significant increase in the frequency of chromosomal abnormalities in patients with severe oligozoospermia was observed when compared to mild oligozoospermia ( P  = 0.01). A statistically significant association ( P  = 0.02) of chromosomal abnormalities and sex chromosome abnormalities ( P  = 0.0001) with azoospermia when compared to oligozoospermia was observed. Conclusions Our results highlight the importance of cytogenetic studies in patients with oligozoospermia (both mild and severe) and non-obstructive azoospermia. The presence of chromosomal abnormalities influences significantly the fertility treatment protocols, as well as provides a definite diagnosis to couples suffering from infertility.

Muntjac deer have experienced drastic karyotype changes during their speciation, making it an ideal model for studying mechanisms and functional consequences of mammalian chromosome evolution. Here we generated chromosome-level genomes for Hydropotes inermis (2n = 70), Muntiacus reevesi (2n = 46), female and male M. crinifrons (2n = 8/9) and a contig-level genome for M. gongshanensis (2n = 8/9). These high-quality genomes combined with Hi-C data allowed us to reveal the evolution of 3D chromatin architectures during mammalian chromosome evolution. We find that the chromosome fusion events of muntjac species did not alter the A/B compartment structure and topologically associated domains near the fusion sites, but new chromatin interactions were gradually established across the fusion sites. The recently borne neo-Y chromosome of M. crinifrons , which underwent male-specific inversions, has dramatically restructured chromatin compartments, recapitulating the early evolution of canonical mammalian Y chromosomes. We also reveal that a complex structure containing unique centromeric satellite, truncated telomeric and palindrome repeats might have mediated muntjacs’ recurrent chromosome fusions. These results provide insights into the recurrent chromosome tandem fusion in muntjacs, early evolution of mammalian sex chromosomes, and reveal how chromosome rearrangements can reshape the 3D chromatin regulatory conformations during species evolution. Muntjac deer underwent rapid species radiation and dramatic chromosome fusions within a short period of time. Here the authors reveal that repeat sequences likely mediated illegitimate recombination to result in chromosome fusions and that 3D chromatin architecture around fusion sites have no significant change, while significant interactions across fusion sites were gradually established after speciation.

Although recent experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking. This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring. We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models. The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA). The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving [almost equal to]35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focalEGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome.

Mitchell, C. R., Azizova, T. V., Hande, M. P., Burak, L. E., Tsakok, J. M., Khokhryakov, V. F., Geard, C. R. and Brenner, D. J. Stable Intrachromosomal Biomarkers of Past Exposure to Densely Ionizing Radiation in Several Chromosomes of Exposed Individuals. Radiat. Res. 162, 257–263 (2004). A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence in human populations of a stable biomarker—intrachromosomal chromosome aberrations—of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, γ rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intrachromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of γ rays. Interchromosome aberration yields were similar in both the high plutonium and the high γ-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as α particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.

The most common type of karyotype abnormality detected in infertile subjects is represented by Klinefelter’s syndrome, and the most frequent non-chromosomal alteration is represented by Y chromosome long arm microdeletions. Here we report our experience and a review of the literature on sperm sex chromosome aneuploidies in these two conditions. Non mosaic 47,XXY Klinefelter patients (12 subjects) show a significantly lower percentage of normal Y-bearing sperm and slightly higher percentage of normal X-bearing sperm. Consistent with the hypothesis that 47,XXY germ cells may undergo and complete meiosis, aneuploidy rate for XX- and XY-disomies is also increased with respect to controls, whereas the percentage of YY-disomies is normal. Aneuploidy rates in men with mosaic 47,XXY/46,XY (11 subjects) are lower than those observed in men with non-mosaic Klinefelter’s syndrome, and only the frequency of XY-disomic sperm is significantly higher with respect to controls. Although the great majority of children born by intracytoplasmic sperm injection from Klinefelter subjects are chromosomally normal, the risk of producing offspring with chromosome aneuploidies is significant. Men with Y chromosome microdeletions (14 subjects) showed a reduction of normal Y-bearing sperm, and an increase in nullisomic and XY-disomic sperm, suggesting an instability of the deleted Y chromosome causing its loss in germ cells, and meiotic alterations leading to XY non-disjunction. Intracytoplasmic injection of sperm from Y-deleted men will therefore transmit the deletion to male children, and therefore the spermatogenic impairment, but raises also concerns of generating 45,X and 47,XXY embryos.    

Introduction In women with a regular cycle, reliable last menstrual period (LMP), and accurate crown–rump length (CRL) estimation, discrepancies in estimated date of delivery (EDD) may indicate impaired fetal growth and increased risk of morbidity. This study examines whether discrepancies between EDD based on LMP (EDDLMP) and CRL (EDDCRL) are associated with chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. Material and Methods A Danish nationwide register‐based cohort study including all singleton pregnancies with both CRL and LMP registered between 2008 and 2018. Exclusion criteria were uncertain LMP, irregular menstrual cycle, EDD discrepancies >±28 days, assisted reproductive technology, and missing outcome data. The cohort was stratified into seven groups according to EDDLMP‐EDDCRL discrepancy. Negative discrepancies indicated smaller‐than‐expected CRL, positive discrepancies indicated larger‐than‐expected CRL, and ±3 days served as reference. Outcomes included chromosomal aberrations, major structural malformations, pregnancy loss, termination of pregnancy, fetal growth restriction, preterm birth, and obstetric complications (preeclampsia, preterm pre‐labour rupture of membranes, placenta previa, and placental abruption). Prevalence with 95% confidence intervals and adjusted odds ratios (aOR) were calculated. Results A total of 262 329 pregnancies were included; 16% had smaller and 21% had larger CRL than expected from LMP. Negative discrepancies were significantly associated with increased risk of chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. In the −8 to −14 days group, 1.28% had a chromosomal abnormality (aOR 2.77 [95% CI 2.30–3.31]), and risk remained elevated among pregnancies at low combined first‐trimester screening risk (aOR 1.95 [1.55–2.43]). For triploidy and trisomy 18, 91% and 59% of cases, respectively, had discrepancies of <−3 days. In the −8 to −14 days group, adverse pregnancy outcome occurred in 11.0% (aOR 1.49 [1.40–1.59]), and 6.5% had obstetric complications, mainly preeclampsia (aOR 1.19 [1.10–1.29]). Conversely, positive discrepancies were associated with reduced risk of chromosomal abnormalities (aOR 0.67 [0.44–0.96]) and adverse pregnancy outcomes (aOR 0.77 [0.69–0.86]) in the +8 to +14 days group. Conclusions A smaller than expected CRL was strongly associated with chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. Incorporating EDD discrepancies into risk algorithms for genetic disease, growth restriction, and preeclampsia may improve prediction and warrants further study. A smaller than expected crown–rump length (CRL) relative to last menstrual period was strongly associated with increased risk of chromosomal abnormalities, adverse pregnancy outcomes, and obstetric complications. Conversely, a larger than expected CRL was associated with a reduced risk of these outcomes.

The aim of present study was to assess the karyotypes of amniotic fluid cells and find the frequency of chromosomal abnormalities and their significance in clinical setting. A total of 15,401 pregnant women were assessed from March 2016 to May 2019, and 14,968 amniotic fluid samples were successfully cultured. These fetuses were grouped according to different indications including advanced maternal age, abnormal nuchal translucency (NT) values, positive first/second trimester screening results, high risk NIPT results, very low PAPP-A and free β-hCG multiples of the normal median (MoM) results, abnormal ultrasound findings or previous history of chromosomal abnormalities. Results indicated the presence of normal karyotype in 90.2% (13,497/14,968) of fetuses. Totally, 46.4% (6945/14,968) of fetuses were 46,XX and 43.8% (6552/14,968) had 46,XY chromosome pattern. A total of 1077 abnormal karyotypes were found among 14,968 fetuses, thus the rate of abnormal fetuses was calculated to be 7.2% (1072/14,968). Meanwhile, a total of 394 cases (2.8%) had a normal polymorphism in their karyotype. In other words, abnormal karyotypes were detected in one of 13.9 cases of patients underwent amniocentesis. Down syndrome, Edward’s syndrome, abnormal mosaicisms and Patau’s syndrome were detected in 4.4% (659/14,968), 0.57% (85/14,968), 0.49% (74/14,968) and 0.24% (36/14,968) of cases, respectively. Sex chromosomal abnormalities including Klinefelter syndrome, Turner syndrome and 47,XXX karyotype were detected in 64 cases (0.43%). In this article, the rates of chromosomal abnormalities are compared between different groups of patients based on the advanced maternal age, abnormal NT values, very low PAPP-A and free β-hCG MoMs results, and positive FTS results. The current investigation provides insight into the most appropriate indications for amniocentesis in Iran.

Livingston, G. K., Falk, R. B. and Schmid, E. Effect of Occupational Radiation Exposures on Chromosome Aberration Rates in Former Plutonium Workers. Radiat. Res. 166, 89–97 (2006). A fluorescence in situ hybridization (FISH) method was used to measure chromosome aberration rates in lymphocytes of 30 retired plutonium workers with combined internal and external radiation doses greater than 0.5 Sv along with 17 additional workers with predominantly external doses below 0.1 Sv. The former group was defined as high-dose and the latter as low-dose with respect to occupational radiation exposure. The two groups were compared to each other and also to 21 control subjects having no history of occupational radiation exposure. Radiation exposures to the high-dose group were primarily the result of internal depositions of plutonium and its radioactive decay products resulting from various work-related activities and accidents. The median external dose for the high-dose group was 280 mSv (range 10–730) compared to a median of 22 mSv (range 10–76) for the low-dose group. The median internal dose to the bone marrow for the high-dose group was 168 mSv (range 29–20,904) while that of the low-dose group was considered negligible. Over 200,000 metaphase cells were analyzed for chromosome aberrations by painting pairs 1, 4 and 12 in combination with a pancentromeric probe. Additionally, 136,000 binucleated lymphocytes were analyzed for micronuclei in parallel cultures to assess mitotic abnormalities arising from damaged chromosomes. The results showed that the frequency of structural aberrations affecting any of the painted chromosomes in the high-dose group correlated with the bone marrow dose but not with the external dose. In contrast, the frequency of micronuclei did not vary significantly between the study groups. The total translocation frequency per genome equivalent × 10−3 ± SE was 4.0 ± 0.6, 9.0 ± 1.1 and 17.0 ± 2.1 for the control, low-dose and high-dose groups, respectively. Statistical analysis of the data showed that the frequency of total translocations and S-cells correlated with the bone marrow dose, with P values of 0.005 and 0.004, respectively. In contrast, these two end points did not correlate with the external dose, with P values of 0.45 and 0.39, respectively. In conclusion, elevated rates of stable chromosome aberrations were found in lymphocytes of former workers decades after plutonium intakes, providing evidence that chronic irradiation of hematopoietic precursor cells in the bone marrow induces cytogenetically altered cells that persist in peripheral blood.

Objective The aim of the present study was to advance the understanding of prenatal diagnostic strategies by systematically analyzing gestational age, duration of pregnancy, clinical indications for prenatal testing, and the prevalence of chromosomal abnormalities among pregnant women undergoing amniocentesis. Materials and methods This retrospective study involved 6,942 pregnant women with indications for amniocentesis who visited the Maternal and Child Health Hospital in Changzhi, Shanxi Province, between January 2018 and December 2023. Both the overall cohort and the subset of positive cases were stratified according to prenatal indications for amniocentesis into the following categories: advanced maternal age (AMA), abnormal maternal serum screening (MSS), noninvasive prenatal testing (NIPT)-positive, pathological ultrasound finding (PUF), parental chromosomal abnormality carrier (PCAC), and poor obstetric history (POH). The analysis encompassed the detection rate of chromosomal abnormalities via amniocentesis, the proportion and positive predictive value (PPV) of each indication group, the distribution of maternal age and gestational age, and the characteristic patterns of confirmed diagnostic findings. Statistical differences were evaluated via the nonparametric Mann–Whitney U test. Results A total of 6,942 samples were included in the study. Of these, 38 samples (0.55%) with completely lost data were excluded. Samples with partially missing data were retained, including 18 cases (0.26%) lacking maternal age information, 23 cases (0.33%) missing gestational age data, and 8 cases (0.12%) without documented indications for prenatal diagnosis. The distribution of valid data was as follows: maternal age was available for 6,886 cases, gestational age was available for 6,882 cases, and prenatal diagnostic indications were available for 6,896 cases. A total of 557 cases of fetal chromosomal abnormalities were diagnosed, with an overall positive rate of 8.07%. Among the 6,882 valid gestational weeks analyzed, the overall range was 15–37 weeks. Specifically, 70.83% fell within 15–20.6 weeks, and 27.08% fell within 21–27.6 weeks, with positivity rates of 6.93% and 10.18%, respectively. A statistically significant difference was observed between the overall and positive groups ( P  < 0.05). Among the 6,886 cases with valid maternal age data, the overall age range was 17–50 years, with no significant difference observed between the overall population and positive cases. When the patients were stratified into A1–A6 age groups, statistically significant differences were observed among all groups except A1 ( P  < 0.05). Among the 6,896 valid cases with recorded prenatal indications, the percentages of MSS, AMA, MSS plus NIPT, NIPT, PUF, POH, and PCAC cases were 51.75%, 30.40%, 0.53%, 4.48%, 7.93%, 2.83%, and 0.40%, respectively. The corresponding PPVs were 4.12%, 8.05%, 94.59%, 42.81%, 8.66%, 5.56%, and 32.14%, respectively. Among the 557 positive cases, chromosomal abnormalities were distributed as follows: aneuploidy (65.35%), structural abnormalities (26.57%), mosaicism (7.18%), and marker chromosomes (0.54%). Autosomal aneuploidy was most frequently represented by trisomy 21, whereas 47,XXY was the most common sex chromosome aneuploidy. Structural abnormalities were most frequently represented by the 17p12 microdeletion. Regarding diagnostic approaches, 27.65% of the cases utilized a single method, 66.96% employed two methods, and 5.39% used three or more methods. Among the single-method cases, Chromosomal Microarray Analysis (CMA) was the most frequently selected technique (14.18%). For cases involving two diagnostic methods, the distribution was as follows (in descending order): karyotype plus QF–PCR (33.21%), QF–PCR plus FISH (17.24%), karyotype plus CMA (10.05%), CMA plus QF–PCR (6.28%), and CNV–seq plus QF–PCR (0.18%). The final analysis revealed that across different age and gestational age subgroups, prenatal indications, diagnostic outcomes, and invasive procedures were most concentrated in the 25–29-year age group and 15–20.6-week gestational age cohort. However, no statistically significant differences were observed among the subgroups ( P  > 0.05). Conclusion This study establishes that a risk-stratified approach optimizes prenatal chromosomal diagnosis: combining maternal serum screening with NIPT enhances detection (PPV 94.59%), while karyotyping and CMA respectively address numerical and structural abnormalities. NIPT proves particularly valuable for advanced maternal age, whereas ultrasound anomalies necessitate CMA. Diagnostic yield remains significant across gestational ages, supporting tailored clinical pathways. These findings underscore the importance of integrating multiple modalities for comprehensive prenatal evaluation.