Unexpected Variation Research Articles

An unexpected variation of occipital and ascending pharyngeal arteries: clinical implications

PurposeThe eight typical External Carotid Artery (ECA) branches are the superior thyroid artery, ascending pharyngeal artery, lingual artery, facial artery, occipital artery, posterior auricular artery, maxillary artery, and superficial temporal artery. The Internal Carotid Artery (ICA) has no branches in the cervical region before entering the carotid canal. We identified a variant of the Occipital Artery (OA) and Ascending Pharyngeal Artery (APA) originating in the cervical portion of the ICA and wish to explore the clinical implications this variation may have.MethodsBetween August and December 2023, 28 formaldehyde donors were dissected in the anatomy course for first-year medical and physician assistant students at the Creighton University School of Medicine, Phoenix campus.ResultsIn one donor, dissection of the right common carotid artery (CCA) revealed a variation of the ECA branches. Two branches were found on the proximal portion of the ICA. After tracing the branches cranially, we identified these as the OA and APA. These two arteries typically originate from the ECA. The bifurcation angle was observed to be nearly 180 degrees. This variation was only observed on the right side.ConclusionAs the prevalence of this variation has only been described in one study, reporting at 0.14%, documentation and education of this anatomy aids surgeons and interventional radiologists in head and neck procedures. Exploring the paths of these ectopic arteries promotes informed decision making and risk stratification for carotid endarterectomy, arterial embolization, bypass procedures, and arterial harvesting. Furthermore, performing thorough imaging such as CT angiograms on patients preoperatively provides better foresight to minimize complications.

Parasitic plants show striking convergence in host preference across angiosperm lineages.

The host specificity of a parasite underpins its ecology, distribution, invasive potential and adaptability, yet for most parasitic plants host ranges are poorly understood. We examine host-parasite relationships across lineages to infer how host specificity may have influenced the evolution of parasitism in plants. Host preference data for all plant holoparasite species were manually collected from literature and herbarium specimens, then analysed to investigate and visualise host diversity and specificity. We reveal a disproportionality in host preference across host lineages: the Asteraceae contains 10% of angiosperm diversity but is infected by 31% of parasite species; meanwhile Monocots comprise 23% but are infected by just 3.2%. Furthermore, we observe striking convergence in host preference: Asteraceae, Euphorbiaceae and Fabaceae are infected by six, five and four independent parasite lineages, respectively. We also demonstrate considerable variation in the degree of host specificity among closely related parasite species; a result that does not reflect the expectation of holoparasites - especially endoparasites - as host specialists. The marked pattern of convergence in preference across disparate lineages points to a common pathway in the evolution of parasitism of eudicots in preference to monocots, which may have in turn have been driven by a divergence in host root and vascular architecture. The unexpected variation in host specificity among closely related species suggests that even apparent generalists may comprise cryptic host-specific taxa. This highlights the value of host preference as an additional consideration in parasitic plant taxonomy. Together, our data point to a complex interplay between ecological and physiological factors driving the evolution of host-parasite interactions. Moreover, they emphasize how little is known about the ecology of most holoparasitic plants, a group of organisms that are especially vulnerable at a time of unprecedented biodiversity loss and extinction.

Cryo-EM structures of the Spo11 core complex bound to DNA.

DNA double-strand breaks that initiate meiotic recombination are formed by the topoisomerase-relative enzyme Spo11, supported by conserved auxiliary factors. Because high-resolution structural data have not been available, many questions remain about the architecture of Spo11 and its partners and how they engage with DNA. We report cryo-electron microscopy structures at up to 3.3-Å resolution of DNA-bound core complexes of Saccharomyces cerevisiae Spo11 with Rec102, Rec104 and Ski8. In these structures, monomeric core complexes make extensive contacts with the DNA backbone and with the recessed 3'-OH and first 5' overhanging nucleotide, establishing the molecular determinants of DNA end-binding specificity and providing insight into DNA cleavage preferences in vivo. The structures of individual subunits and their interfaces, supported by functional data in yeast, provide insight into the role of metal ions in DNA binding and uncover unexpected structural variation in homologs of the Top6BL component of the core complex.

Elimination of physiological senescent cutaneous cells in a novel p16-dependent senolytic mouse model impacts lipid metabolism in skin aging.

The evidence of the correlation between cellular senescence and aging has increased in research with animal models. These models have been intentionally generated to target and regulate cellular senescent cells with the promoter activity of p16Ink4a or p19Arf, genes that are highly expressed in aging cells. However, the senolytic efficiency in various organs and cells from these models represents unexpected variation and diversity in some cases. We have generated a novel knock-in model, p16tdT-hDTR mice, which possess tdTomato and human diphtheria toxin receptor (hDTR) downstream of Cdkn2a, an endogenous p16Ink4a gene. We successfully demonstrated that p16-derived tdTomato and hDTR expressions are observed in these mouse embryo fibroblasts and following treatment with diphtheria toxin (DT) eliminates those cells. Furthermore, we demonstrated the efficacy of eliminating p16-positive cells in vivo, and also observed a tendency to decrease their cutaneous SA-β-gal activity after subcutaneous DT injection into p16tdT-hDTR mice. In particular, comprehensive gene expression analysis in skin revealed that upregulated genes related to lipid metabolisms with aging exhibited remarkable expressions under the senolysis. These results clearly unveiled p16-positive senescent cells contribute to age-related changes in skin.

Dynamic analysis of the tethered satellite system considering uncertain but bounded parameters

Dynamic analysis of the tethered satellite system (TSS) can provide a fundamental guideline to the evaluation of performance and robust design of the system examined. Uncertainties inherited with the parameters would induce unexpected variation of the response and deteriorate the reliability of the system. In this work, the effect of uncertain mass of the satellites on the deployment and retrieval dynamics of the TSS is investigated. First the interval mode is employed to take the variation of mass of satellite into account in the processes of deployment and retrieval. Then, the Chebyshev interval method is used to obtain the lower and upper response bounds of the TSS. To achieve a smooth and reliable implementation of deployment and retrieval, the nonlinear programming based on the Gauss pseudo-spectral method is adopted to obtain optimal trajectory of tether velocity. Numerical results show that the uncertainties of mass of the satellites have a distinct influence on the response of tether tension in the processes of deployment and retrieval.

Unexpected variation in outcomes following total (procto)colectomies for ulcerative colitis in New South Wales, Australia: a population-based 19-year linked-data study.

Total (procto)colectomy for ulcerative colitis (UC) is associated with significant morbidity, which is increased in the emergency setting. This study aimed to evaluate the outcomes following total (procto)colectomies at a population level within New South Wales (NSW), Australia, and identify case mix and hospital factors associated with these outcomes. A retrospective data linkage study of patients undergoing total (procto)colectomy for UC in NSW over a 19-year period (2001-2020) was performed. The primary outcome was 90-day mortality. The influence of hospital level factors (including annual volume) and patient demographic variables on outcomes was assessed using logistic regression. Temporal trends in annual volume and evidence for centralization were assessed. In all, 1418 patients (mean 47.0 years [SD 18.7], 58.7% male) underwent total (procto)colectomy during the study period. The overall 90-day mortality rate was 3.2% (emergency 8.6% and elective 0.8%). After adjusting for confounding, increasing age at total (procto)colectomy, higher comorbidity burden, public health insurance (Medicare) status, emergency operation and living outside a major city were significantly associated with increased mortality. Hospital volume was significantly associated with mortality at a univariate level, but this did not persist on multivariate modelling. Outcomes of UC patients undergoing total (procto)colectomy in NSW Australia are comparable to international experience. Whilst higher mortality rates are observed in low volume and public hospitals, this appears attributable to case mix and acuity rather than surgical volume alone. However, as inflammatory bowel disease surgery is not centralized in Australia, only one NSW hospital performed >10 UC total (procto)colectomies annually. Variation in mortality according to insurance status and across regional/remote areas may indicate inequality in the availability of specialist inflammatory bowel disease treatment, which warrants further research.

Transcriptional profiling of retinal astrocytes identifies a specific marker and points to functional specialization.

Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the "classical" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.

Method for stabilizing the detection efficiency of grazing angle incidence boron-lined neutron detectors

Boron-lined gaseous neutron detectors intrinsically suffer from the “self-absorption” effect and hence their neutron detection efficiencies might be nonconstant, when the threshold of them undergoes unexpected variation. To address this problem, we propose a maximum likelihood estimation-based threshold determining method, via which the pulse height spectra acquired under different high voltages could be rescaled to the same abscissa axis of deposited energies. Monte Carlo simulations were conducted to study the relationship between the precision of the threshold determination and the counting statistics, as well as the energy deposition spectrum, indicating that the grazing angle incidence neutron detector can achieve a fairly small relative standard variation for a spectrum with a modest total neutron counts. A prototype grazing angle incidence neutron detector has been constructed and tested under high voltages ranging from 500 V to 950 V. The experimental results show that, with the maximum likelihood estimation-based method, the threshold's relative standard deviations are less than 10% even with a total neutron counts as low as 100. As a result, the maximum relative variance of the counting plateau curve is 4.8% in the region of [500 V, 900 V] when the detector operates at a grazing angle of 1.8°. The results presented in this study indicate that combining the grazing angle incidence and the maximum likelihood estimation-based threshold determining method would be a promising way to achieve stable neutron detection efficiency for neutron detectors with the boron layer as the neutron convertor.

Variation of Activation Volume as an Indicator of the Difference in Clusterization Phenomenon Induced by H-Bonding and F-Π Stacking Interactions in Enantiomers and a Racemate of Flurbiprofen.

In this paper, X-ray diffraction (XRD), differential scanning calorimetry (DSC), broadband dielectric (BDS), and Fourier transform infrared (FTIR) spectroscopy supported by molecular dynamics (MD) simulations and quantum chemical computations were applied to investigate the structural and thermal properties, molecular dynamics, and H-bonding pattern of R-, S-, and RS-flurbiprofen (FLP). Experimental data indicated various spatial molecular arrangements in crystalline forms of examined systems, which seemed to disappear in the liquid state. Surprisingly, deeper analysis of high-pressure dielectric data revealed unexpected variation in the activation volume of pure enantiomers and a racemate. MD simulations showed that it is an effect of the clusterization phenomenon and a higher population of small associates in the former samples. Moreover, theoretical consideration exposed the particular role of unspecific F-Π interactions as a driving force underlying local molecular arrangements of molecules in the liquid and the crystal lattice of R-, S-, and RS-FLP.

Discovery of a Biotin Synthase That Utilizes an Auxiliary 4Fe-5S Cluster for Sulfur Insertion.

Biotin synthase (BioB) is a member of the Radical SAM superfamily of enzymes that catalyzes the terminal step of biotin (vitamin B7) biosynthesis, in which it inserts a sulfur atom in desthiobiotin to form a thiolane ring. How BioB accomplishes this difficult reaction has been the subject of much controversy, mainly around the source of the sulfur atom. However, it is now widely accepted that the sulfur atom inserted to form biotin stems from the sacrifice of the auxiliary 2Fe-2S cluster of BioB. Here, we bioinformatically explore the diversity of BioBs available in sequence databases and find an unexpected variation in the coordination of the auxiliary iron-sulfur cluster. After in vitro characterization, including the determination of biotin formation and representative crystal structures, we report a new type of BioB utilized by virtually all obligate anaerobic organisms. Instead of a 2Fe-2S cluster, this novel type of BioB utilizes an auxiliary 4Fe-5S cluster. Interestingly, this auxiliary 4Fe-5S cluster contains a ligated sulfide that we propose is used for biotin formation. We have termed this novel type of BioB, Type II BioB, with the E. coli 2Fe-2S cluster sacrificial BioB representing Type I. This surprisingly ubiquitous Type II BioB has implications for our understanding of the function and evolution of Fe-S clusters in enzyme catalysis, highlighting the difference in strategies between the anaerobic and aerobic world.

Labor supply responses to rainfall shocks

AbstractAgricultural production in developing countries is heavily rainfall dependent. Any unexpected variation in rainfall can affect the welfare of households. Using unit record data from India, this paper shows that households can insure against agricultural productivity (rainfall) shocks. Evidence suggests that they do so by varying the time allocation of individual members to different activities, particularly to regular wage work and human capital accumulation. There is a gender‐differentiated aspect to this response. Rainfall shocks adversely affect women's human capital accumulation. While there is no evidence that households use participation in NREGS to insure against rainfall shocks, the availability of NREGS helps reduce the impact of rainfall shocks on human capital accumulation.

Liver transplant recipients with polycystic liver disease have longer waiting times but better long-term clinical outcomes than those with liver disease due to other causes: A retrospective cross-sectional study.

Liver transplantation is the only curative option for patients with polycystic liver disease (PLD). In the United Kingdom, these patients are listed on the variant syndrome list due to their preserved liver function reflected in the United Kingdom End-stage Liver Disease (UKELD) score. The transplantation and survival rates for this patient group in the UK have not been previously reported. A retrospective cross-sectional analysis of patients receiving liver transplantation between 2010 and 2017 was performed using the NHS blood and transplantation database. This database contains the demographic, clinical parameters, indication for transplantation and follow-up of all patients in UK-based transplant centres. Basic statistics was performed using SPSS version 27. 5412 recipients received elective liver allografts in the study period. 1.6% (100) of recipients had PLD as their primary indication for transplantation with 60 receiving liver only allografts and 40 receiving combined liver-kidney allografts. PLD patients had a >3-fold longer mean waiting time for transplantation compared to non-PLD patients, 508 days v 154 days respectively. PLD patients receiving combined liver-kidney allografts had a longer waiting time than those receiving a liver only allograft, 610 days v 438 days respectively. There were comparable patient survival rates for people with PLD and non-PLD primary indications at 30 days (94.0% vs 97.6%) and 1 year (92.0% vs 93.2%) but improved survival rates at 5 years (81.3% vs 76.5%). There were also comparable allograft survival rates for people with PLD and non-PLD primary indications at 30 days (93.9% vs 95.3%) and 1 year (91.9% vs 91.2%) but improved survival rates at 5 years (82.5% vs 77.3%). Transplant centre-level analysis identified variation in the proportion of liver transplantations for people with PLD as their primary listed indication. Patients with PLD wait significantly longer for liver transplantation compared to other indications. However, transplanted PLD patients demonstrate better longer-term patient and liver allograft survival rates compared to transplanted non-PLD patients. The unexpected variation between individual UK centres transplanting for PLD deserves further study.

Thermal tolerance of giant salmonfly nymphs (Pteronarcys californica) varies across populations in a regulated river.

Warming of aquatic ecosystems is transforming the distribution, phenology and growth of the organisms dependent upon these ecosystems. Aquatic insects such as stoneflies are especially vulnerable to warming because the aquatic nymph stage of their life cycle depends on cool, well-oxygenated, flowing water habitat. We tracked thermal effects on available aerobic capacity of the aquatic nymph stage of an iconic and vulnerable stonefly species, the giant salmonfly (Pteronarcys californica), to compare habitat thermal regime measurements for two salmonfly populations from habitats separated by a gradient in summer weekly maximum temperatures. Contrary to expectations, the thermal optima range of the warmer habitat population was cooler than for the cooler habitat population. We posit that this unexpected interpopulation variation in thermal response is more strongly driven by diel and seasonal thermal variability than by the highest summer temperatures experienced within respective habitats. Additionally, we show that summer daily maximum temperatures could result in periodic limits in available aerobic capacity to support work of the warmer habitat nymphs and may be the mechanism underlying reduced abundance relative to the upstream cooler habitat population. Our findings provide insight into potential thermal and metabolic mechanisms that could regulate the success of ecological and culturally important aquatic insect species experiencing global change. We conclude that thermal regimes and thermal variation, not just mean and maximum temperatures, are critical drivers of aquatic insect responses to water temperatures.

Understanding fatality patterns and sex ratios of Brazilian free-tailed bats (Tadarida brasiliensis) at wind energy facilities in western California and Texas

Background Operation of wind turbines has resulted in collision fatalities for several bat species, and one proven method to reduce these fatalities is to limit wind turbine blade rotation (i.e., curtail turbines) when fatalities are expected to be highest. Implementation of curtailment can potentially be optimized by targeting times when females are most at risk, as the proportion of females limits the growth and stability of many bat populations. The Brazilian free-tailed bat (Tadarida brasiliensis) is the most common bat fatality at wind energy facilities in California and Texas, and yet there are few available data on the sex ratios of the carcasses that are found. Understanding the sex ratios of fatalities in California and Texas could aid in planning population conservation strategies such as informed curtailment. Methods We used PCR to determine the sex of bat carcasses collected from wind energy facilities during post-construction monitoring (PCM) studies in California and Texas. In California, we received samples from two locations within the Altamont Pass Wind Resource Area in Alameda County: Golden Hills (GH) (n = 212) and Golden Hills North (GHN) (n = 312). In Texas, we received samples from three wind energy facilities: Los Mirasoles (LM) (Hidalgo County and Starr County) (n = 252), Los Vientos (LV) (Starr County) (n = 568), and Wind Farm A (WFA) (San Patricio County and Bee County) (n = 393). Results In California, the sex ratios of fatalities did not differ from 50:50, and the sex ratio remained stable over the survey years, but the seasonal timing of peak fatalities was inconsistent. In 2017 and 2018, fatalities peaked between September and October, whereas in 2019 and 2020 fatalities peaked between May and June. In Texas, sex ratios of fatalities varied between locations, with Los Vientos being female-skewed and Wind Farm A being male-skewed. The sex ratio of fatalities was also inconsistent over time. Lastly, for each location in Texas with multiple years studied, we observed a decrease in the proportion of female fatalities over time. Discussion We observed unexpected variation in the seasonal timing of peak fatalities in California and differences in the sex ratio of fatalities across time and facility location in Texas. In Texas, proximity to different roost types (bridge or cave) likely influenced the sex ratio of fatalities at wind energy facilities. Due to the inconsistencies in the timing of peak female fatalities, we were unable to determine an optimum curtailment period; however, there may be location-specific trends that warrant future investigation. More research should be done over the entirety of the bat active season to better understand these trends in Texas. In addition, standardization of PCM studies could assist future research efforts, enhance current monitoring efforts, and facilitate research on post-construction monitoring studies.

Quantile connectedness of oil price shocks with socially responsible investments

We use a new method to disentangle various sources of oil price shocks and find how these sources are connected to major global environmental, social, and governance (ESG) equity indices under extreme market movements using daily data from October 2007 to March 2022. Our quantile-based connectedness analysis shows that return connectedness considerably amplifies with the size of the shock for both positive and negative shocks, indicating that oil shocks spread more intensely during extreme market movements. We also find that oil shocks originating from unexpected variation in demand and risk substantially contribute to the variation in the ESG returns while supply shocks have relatively little effect when estimated at the median level but the contribution of all different types of shocks remain extremely high when analyzed at the tails. Our results indicate that socially responsible investments are prone to contagion and thus offer limited portfolio diversification benefits under extreme market movements. One clear implication of our study is that investors need to carefully design their risk management and diversification strategies to account for not only the source of the oil shocks but also the magnitude of the oil shock on their green equity investments. We also show that total dynamic connectedness significantly increased during the global financial crisis, European debt crisis, the Brexit episode and the recent COVID-19 outbreak.

Analysis of programmed frameshifting during translation of prfB in Flavobacterium johnsoniae.

Ribosomes of Bacteroidia fail to recognize Shine-Dalgarno (SD) sequences due to sequestration of the 3' tail of the 16S rRNA on the 30S platform. Yet in these organisms, the prfB gene typically contains the programmed +1 frameshift site with its characteristic SD sequence. Here, we investigate prfB autoregulation in Flavobacterium johnsoniae, a member of the Bacteroidia. We find that the efficiency of prfB frameshifting in F. johnsoniae is low (∼7%) relative to that in Escherichia coli (∼50%). Mutation or truncation of bS21 in F. johnsoniae increases frameshifting substantially, suggesting that anti-SD (ASD) sequestration is responsible for the reduced efficiency. The frameshift site of certain Flavobacteriales, such as Winogradskyella psychrotolerans, has no SD. In F. johnsoniae, this W. psychrotolerans sequence supports frameshifting as well as the native sequence, and mutation of bS21 causes no enhancement. These data suggest that prfB frameshifting normally occurs without SD-ASD pairing, at least under optimal laboratory growth conditions. Chromosomal mutations that remove the frameshift or ablate the SD confer subtle growth defects in the presence of paraquat or streptomycin, respectively, indicating that both the autoregulatory mechanism and the SD element contribute to F. johnsoniae cell fitness. Analysis of prfB frameshift sites across 2686 representative bacteria shows loss of the SD sequence in many clades, with no obvious relationship to genome-wide SD usage. These data reveal unexpected variation in the mechanism of frameshifting and identify another group of organisms, the Verrucomicrobiales, that globally lack SD sequences.

Information distance: Conceptual development and empirical tests of a novel measure of cross-national distance

Socio-political risks (SPRs) are important drivers of firm-level risk. Beyond unexpected variation in socio-political environments over time, the difference between home and host country socio-political contexts induces risk as it increases the difficulty to understand a foreign environment. This risk is specifically important for internationally active firms, as they need to gather and interpret information stemming from different socio-political environments to manage their international operations. However, existing literature lacks both concept and measure to capture such information asymmetry. In this paper, we explain how cross-national distance is related to SPRs through information asymmetry, and develop a reflective measure of cross-national distance based on information theory, signal analysis, and financial market information. Conceptual and empirical evaluations and applications of the concept and measure proposed provide support for our approach.

Intragenomic rDNA variation - the product of concerted evolution, mutation, or something in between?

The classical model of concerted evolution states that hundreds to thousands of ribosomal DNA (rDNA) units undergo homogenization, making the multiple copies of the individual units more uniform across the genome than would be expected given mutation frequencies and gene redundancy. While the universality of this over 50-year-old model has been confirmed in a range of organisms, advanced high throughput sequencing techniques have also revealed that rDNA homogenization in many organisms is partial and, in rare cases, even apparently failing. The potential underpinning processes leading to unexpected intragenomic variation have been discussed in a number of studies, but a comprehensive understanding remains to be determined. In this work, we summarize information on variation or polymorphisms in rDNAs across a wide range of taxa amongst animals, fungi, plants, and protists. We discuss the definition and description of concerted evolution and describe whether incomplete concerted evolution of rDNAs predominantly affects coding or non-coding regions of rDNA units and if it leads to the formation of pseudogenes or not. We also discuss the factors contributing to rDNA variation, such as interspecific hybridization, meiotic cycles, rDNA expression status, genome size, and the activity of effector genes involved in genetic recombination, epigenetic modifications, and DNA editing. Finally, we argue that a combination of approaches is needed to target genetic and epigenetic phenomena influencing incomplete concerted evolution, to give a comprehensive understanding of the evolution and functional consequences of intragenomic variation in rDNA.

Potent and uniform fetal hemoglobin induction via base editing.

Inducing fetal hemoglobin (HbF) in red blood cells can alleviate β-thalassemia and sickle cell disease. We compared five strategies in CD34+ hematopoietic stem and progenitor cells, using either Cas9 nuclease or adenine base editors. The most potent modification was adenine base editor generation of γ-globin -175A>G. Homozygous -175A>G edited erythroid colonies expressed 81 ± 7% HbF versus 17 ± 11% in unedited controls, whereas HbF levels were lower and more variable for two Cas9 strategies targeting a BCL11A binding motif in the γ-globin promoter or a BCL11A erythroid enhancer. The -175A>G base edit also induced HbF more potently than a Cas9 approach in red blood cells generated after transplantation of CD34+ hematopoietic stem and progenitor cells into mice. Our data suggest a strategy for potent, uniform induction of HbF and provide insights into γ-globin gene regulation. More generally, we demonstrate that diverse indels generated by Cas9 can cause unexpected phenotypic variation that can be circumvented by base editing.

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

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