Inversion Carrier Research Articles

Molecular Cytogenetic Characterization of Rare but Repeatedly Observed Inversions in German Population

Introduction: The term inversion refers to an aberration caused by two breakage and fusion events found in one or both arms of a chromosome. The presence of such aberrations can but must not be associated with infertility or unbalanced products of conception. Normally, inversions are not associated with phenotypic alterations for the carrier. Despite the fact that most such inversions are de novo and unique, recurrent breakpoints have also been reported. Methods: Here two recurrent paracentric inversions in the long arm of chromosomes 11 and 12 and a pericentric one in chromosome 10 were studied in at least 10 unrelated (infertile) patients, each. Breakpoints were narrowed down by fluorescence in situ hybridization applying locus-specific bacterial artificial chromosome-derived probes. Results: Molecular cytogenetically identical breakpoints could be characterized for all three studied inversions. Pericentric inversion inv(10)(p11.21q21.2), previously reported to be of single origin and distributed mainly in Northern Europe, could be found to be present all over Germany, too. In the studied cases with paracentric inversion inv(11)(q21q23.3), recurrent breakpoints were found in all parts of Germany, as well; however, additional 2 cases with slightly different breakpoints were characterized besides. Most interestingly, inversion inv(12)(q14.1∼14.2q24.11∼24.13) had always the same recurrent breakpoints and presented an exclusive occurrence in North-Western part of Germany. Conclusion: Overall, (at least) three different cytogenetically detectable recurrent inversions were characterized here. This highlights that such events may be more frequent in human population than yet suggested. Accordingly, such events might even spread in (middle European) human population. Specific impact on reproduction and fitness of inversion carriers characterized here seems to be negligible. Nonetheless, such recurrent rearrangements need more attention as they may provide valuable information for genetic counseling in future.

Enhancing the Tunable Sensitivity of a Near-Ultraviolet to Visible to Near-Infrared Photo Irradiance Sensor Using an Indium Tin Oxide-Aluminum Oxide-Zirconia Aluminum Oxide-Silicon

This study focuses on enhancing the tunable sensitivity of a photo irradiance sensor (PIS) operating in the near-ultraviolet to visible to near-infrared (NUV-VIS-NIR) spectrum using an indium tin oxide-aluminum oxide-zirconia aluminum oxide-silicon oxide-silicon capacitor (hereafter IAZAOS). Unlike other PIS designs such as reverse-biased metal–insulator–semiconductor (MIS) and tunneling MIS, the IAZAOS PIS measures changes in inversion capacitance under strong forward bias with light irradiation. The IAZAOS PIS offers several key advantages over alternative designs. It exhibits high sensitivity, weak bias dependence, low dark current, tunable sensitivity, low power consumption, CMOS process compatibility, simple low-cost manufacturing, and good gate oxide reliability. Under 1 mW/cm2 irradiation at 1 kHz, the inversion carrier concentration reaches approximately 70% saturation. The resolution achieved is 10 nW/cm2 at 1 kHz, with a sensing range spanning from 10 nW/cm2 to 1 W/cm2 across frequencies from 1 kHz to 100 kHz. These performance characteristics surpass those reported for other PIS technologies. Furthermore, the IAZAOS PIS demonstrates a quantum efficiency of about 60% at 405 nm, which surpasses the quantum efficiency of general silicon-based p(i)n diodes. Post-deposition annealing techniques are employed to enhance the sensor’s performance. Dielectric annealing improves the ZrAlOx interface trap and permittivity properties, while conducting oxide annealing enhances indium tin oxide transmission and resistivity. The combination of these treatments results in a high-speed, high-sensitivity, high-resolution, and reliable NUV-VIS-NIR sensing capability for the IAZAOS capacitor-based PIS.

A Surface Potential Model for Metal-Oxide-Semiconductor Transistors Operating near the Threshold Voltage

Device physics and accurate transistor modeling are necessary to reduce the operating voltage near the threshold for power-constrained circuits. Conventional device modeling for metal-oxide-semiconductor (MOS) transistors focuses on operations in either strong or weak inversion regimes, and the electrostatics at gate biases near the threshold voltage is rarely studied. This research proposed an analytical model to describe the distribution of the surface potential along the channel for near-threshold operation. Numerical device simulations were also performed to investigate the electrostatics near the threshold voltage. The numerical simulation with constant carrier mobility showed an overshoot in the transconductance due to decay of the lateral electric field with gate bias. The decay of the lateral electric field was predicted by the proposed analytical surface potential model which considered widening the channel length with flooding of the inversion carriers in the channel and gate overlap regions. The channel length widening effect saturated as the gate bias further increased. Therefore, evident transconductance overshoot was observed near the threshold voltage in short-channel devices.

(Invited) Physical Understanding of HfZrO2/Si FeFET Memory and Its AI Applications

Si-friendly HfO2-based FeFETs have been well recognized as a technology booster for future integrated memory applications, which are expected to enhance the energy efficiency of AI computation. In this paper, we present our recent studies on the understanding of the coupling between polarization, inversion-layer charges, and carrier traps in HfZrO2 (HZO)/Si FeFET memory. Discrimination of polarization, inversion carriers, and trapped carriers is realized by combining P-V, quasi-split C-V, and Hall measurements of FeFETs. Polarization and electron/hole-trap interactions significantly affect the performance and characteristics of HZO/Si FeFETs. A large number of electron traps can enhance polarization and the memory window of n-FeFETs, while there are almost no hole traps, leading to the smaller memory window of p-FeFETs. We have also proposed a new scheme of physical reservoir computing with parallel data processing for speech recognition by using HZO/Si FeFETs. A high classification accuracy of 95.9 % has been experimentally demonstrated in the task to classify the audio waveforms of ‘0’ to ‘9’ spoken digits.

Higher chromosomal abnormality rate in blastocysts from a subset of patients with pericentric inversion (Inv) 1 variant

The purpose of this study was to evaluate the incidence of unbalanced chromosome rearrangement in blastocyst-stage embryos from carriers of pericentric inversion of chromosome 1 (PEI-1). A total of 98 embryos from 22 PEI-1 carriers were tested for unbalanced rearrangements, originating from inversion carriers, and overall aneuploidy. Logistic regression analysis indicated that the ratio of inverted segment size to chromosome length was a statistically significant risk factor for unbalanced chromosome rearrangement from PEI-1 carriers (p = 0.003). The optimal cut-off values to predict the risk of unbalanced chromosome rearrangement was 36%, with the incidence being 2.0% in the <36% group and 32.7% in the ≥36% group. The unbalanced embryo rate was 24.4% in male carriers compared to 12.3% in female carriers. Inter-chromosomal effect analysis was performed using 98 blastocysts from PEI-1 carriers and 116 blastocysts from age-matched controls. PEI-1 carriers had similar sporadic aneuploidy rates compared to those of age-matched controls at 32.7 vs. 31.9%, respectively. In conclusion, the risk of unbalanced chromosome rearrangement is affected by inverted segment size in PEI-1 carriers.

The Limit Tuning Effects Exerted by the Mechanically Induced Artificial Potential Barriers on the I-V Characteristics of Piezoelectric PN Junctions.

A mechanically induced artificial potential barrier (MIAPB) in piezoelectric semiconductor devices is set up under the action of a pair of tensile/compressive mechanical loadings. Three factors, namely, the barrier height, width and position, affect the nature and extent of interaction between the MIAPB and the contact barrier, and the tuning characteristics (generated under conditions of the artificial barrier) of the piezoelectric PN junctions were studied. The influence of these factors resulted in variations in the interaction intensities, superposition effects, carrier inversion degrees and carrier redistribution ranges. Subsequently, the limit tuning effects exerted by the tensile/compressive-mode MIAPB on the PN junctions were studied. The inconsistency between the left and right end of the tensile-mode MIAPB under conditions of the offset loading state proves that the maximum tuning effect is generated when both sides of the interface are symmetrically loaded. The range of carrier redistribution and the over-inversion of local carriers, affected by the width and height of MIAPB, result in a second competitive mechanism. The carrier redistribution range and the carrier inversion degree require that the compressive-mode MIAPB be sufficiently wide. The interaction intensities and the superposition effects, affected by the position and height of the MIAPB, contribute to the second competing mechanism. We logically clarify the relationship between multiple competition and find that the emergence of multiple competitive mechanisms proves the existence of the limit tuning effect of MIAPB on the I-V properties of PN junctions. The results reported herein provide a platform for understanding the mechanical tuning laws governing the functions of piezoelectric PN junctions and piezoelectric devices.

Do chromosomal inversion carriers really need preimplantation genetic testing?

This study aimed to evaluate the rates of euploidy, aneuploidy, and mosaicism in preimplantation genetic testing for structural rearrangements (PGT-SR) cycles from chromosomal inversion carriers. In addition, this work also focused on assessing the impact of some contributors on the incidence of parental originating aneuploidy and mosaicism. This retrospective review enrolled chromosomal inversion carrier couples of whom the females were under 38years old undergoing PGT-SR at a single academic reproductive center. Subgroups were divided according to the gender of carriers, the inversion type, and the semen parameters of male carriers (male factor infertility (MF) or non-MF). Patient demographics, cycle characteristics, and PGT-SR outcomes were compared among subgroups. A total of 71 PGT-SR cycles from 57 inversion carrier couples were included for analysis. Among the 283 blastocysts, 48.4% were identified as euploidy, 27.9% as aneuploidy, and the remaining 23.7% as mosaicism. Only 32.9% of aneuploid embryos and 1.5% of mosaic embryos involved the parental inversion chromosomes. Notably, the female inversion carriers seemed to produce more parental originating aneuploid embryos than male inversion carriers (45.5% vs 23.9%, p = 0.044). The type of inversion and sperm parameters of male chromosomal inversion carriers did not affect the ploidy status of embryos. The incidence of parental originating aneuploidy in inversion carrier couples is lower than expected. For male chromosomal inversion carriers with normal sperm condition whose female partners are under 38years old, natural conception combined with prenatal diagnosis could be provided as an option during fertility counseling.

Compressive Strained Si1-XGex Channel for High Performance Gate-All-Around Nanosheet Transistors

As scaling of conventional FinFET architecture to achieve target transistor density and performance becomes more complex and difficult, it is essential to attain a next generation transistor architecture. Horizontal Gate-All-Around (hGAA) nanosheet (NS) devices have attracted attention as a candidate to replace FinFETs at the 5nm technology node and beyond due to their excellent electrostatics and short channel control. Compared to scaled FinFET, stacked GAA NS offers circuit performance improvements with increased effective width per active footprint while also enabling gate length scaling. Exploring performance improvement techniques, such as channel strain engineering, is important for next generation CMOS technologies. It is difficult, however, to effectively induce strain into the channel region using source/drain stressors in scaled GAA NS structures due to reduction of the stressor (embedded SiGe in source/drain region) volume as transistor dimension shrinks. In addition, strain relaxation of source/drain stressors caused by introduction of crystalline defects decreases effectiveness to induce strain into the channel region. This is more pronounced by the fact that achieving superior epitaxial growth is more difficult on the GAA NS device structure due to the presence of inner spacer dielectric. Therefore, we proposed a stacked GAA NS pFET device with compressively strained SiGe channel. The SiGe channel NS devices were fabricated using Si NS channel trimming by selective isotropic dry etch and selective SiGe epitaxial growth techniques after the Si NS channel release (Fig. 1). This is the preferable scheme in terms of strain retention in the SiGe channel NS region since there are no patterning processes that cause strain relaxation during downstream processing.To investigate the device characteristics of SiGe NS devices, we fabricated strained Si1-xGex (x = 0.2, 0.25, 0.3, and 0.35) channel NS pFET and investigated the crystallinity and strain in the channel region. Fig. 2 contains cross-sectional TEM images across the gate after Si0.7Ge0.3 channel formation. We observed no visible crystalline defects in the 4 nm-thick Si0.7Ge0.3 layer grown on the 2 nm-thick trimmed Si NS, indicating superior crystallinity of Si0.7Ge0.3 layer. To investigate strain in the nanoscale strained SiGe NS channel structures, Precession Electron Diffraction (PED) characterization was performed to evaluate lattice deformation of the stacked SiGe NS channel with 4 nm-thick Si0.7Ge0.3 epitaxial growth. Lattice deformation values are defined as the difference between in-plane lattice constants and the Si lattice constant, normalized by the Si lattice constant. Fig. 3 shows in-plane lattice deformation contour maps in the region of the stacked SiGe NS channel obtained from both X-cut (across the gate) and Y-cut (along the gate) for the SiGe NS structure with sheet width of 20 nm. The in-plane lattice deformation values were extracted from the middle of the SiGe NS channel as shown in Fig. 4. Preservation of half the amount of strain along the channel direction ([110]) was confirmed whereas strain along the NS width direction ([1-10]) was found to be almost fully relaxed due to elastic relaxation. This results in the Si0.7Ge0.3 channel being uniaxially stressed. The compressive stress along the channel direction estimated from the [110] lattice deformation is ~1 GPa.Normalized hole mobility in the representative Si1-xGex channel NS pFET as a function of inversion carrier density (Ninv) is shown in Fig. 5. The hole mobility of Si1-xGex channel (x = 0.35) with Si cap is almost 100% higher than that of Si NS channel. The mobility benefit of Si1-xGex channel is attributed to reduced effective hole mass along the transport direction caused by a high compressive strain in the Si1-xGex channel.The technique demonstrated in this study for forming compressively strained SiGe channel NS has great potential to improve pFET device performance for next generation of CMOS logic in GAA Nanosheet technology. Figure 1

Compact drain current modeling of planar InGaAs quantum well MOSFET

In this article, we propose a physics-based compact drain current model of planar InGaAs channel-based quantum well MOS transistor. The effects of essential physical phenomenon such as quantum confinement, multiple sub-band energies, wavefunctions and perturbations in sub-band energies are considered in the model by deriving the time-independent Schroedinger wave equation. The potential and inversion carrier profiles are obtained through direct solution of Schroedinger and Poisson equations inside the device. The proposed model also considers other important physical aspects such as band non-parabolicity, velocity overshoot and threshold voltage roll-off. The model is thus physics-based and does not include any empirical fitting parameter. Professional numerical simulator data for a variety of bias voltages and channel thicknesses have been used to validate the expected outcomes of our model. A reasonable agreement between the transistor characteristics as predicted by our model and that available experimentally is obtained, thus justifying the accuracy of our model.

P-549 Paraclinical and spermogram evaluation of infertile males with balanced chromosomal rearrangements referred to Royan institute from 2009-2021

Abstract Study question Whether balanced chromosomal rearrangements are associated with altered semen parameters/increased DNA Fragmentation Index (DFI), are the common breakpoints related to male infertility in patients ? Summary answer Balanced chromosomal rearrangements is associated with abnormal semen parameters and increased DFI in carriers. Chromosomes 9,1,3 showed the highest incidence of chromosomal rearrangement What is known already Among many factors, balanced chromosomal rearrangements are thought to be one of the major genetic factors influencing male infertility which can cause disorders related to spermogram, DNA fragmentation, increased risk of miscarriage and ART failure. Finding common chromosomal breakpoints in infertile men carrying balanced chromosomal translocations is significant since these patients usually possess normal clinical features. Numerous studies have been performed on the various chromosome translocations. However, there has not been any report on the common breakpoints in balanced chromosomal abnormalities related to male infertility in Iran. Study design, size, duration This cross-sectional study performed on 25000 patients’ files admitted to the Royan institute during the period 2009- 2021.Infertile men carrying balanced chromosomal rearrangements were included as case group. Sperm parameters, DFI and common chromosomal break points were evaluated Participants/materials, setting, methods 25000 files of patients were reviewed. 252 infertile men carrying balanced chromosomal rearrangements and 252 men with normal karyotype were included (case and control group, respectively). Sperm concentration, motility (CASA), sperm morphology (Papanicolaou Staining),DFI (SCSA) and cytogenetic analysis of peripheral blood lymphocytes (G-banding) were evaluated. Numerical chromosomal abnormalities, deletions, marker chromosomes, alcohol or drug addiction, smoking, chemotherapy and radiation, varicocele and exposure to environmental pollution were excluded. The common chromosomal breakpoints in translocations were investigated. Main results and the role of chance Sperm concentration, total motility and normal morphology were significantly lower in balanced chromosomal rearrangements carriers compared to control group(p &amp;lt; 0.05). DFI in patient was significantly higher in comparison to control group(p &amp;lt; 0.05). Among different kind of chromosomal rearrangement carriers’, sperm concentration and total motility were lower in Robertsonian translocation carriers comparing to the Reciprocal translocation and inversion ones. The reciprocal translocation and inversion carriers did not differ regarding to sperm concentration and total motility. Meanwhile, normal morphology was lower in the translocation compared to inversion carriers. No difference was observed in DFI among carriers of balanced chromosomal rearrangements. Among case group, inversion accounted for the largest share, followed by Reciprocal, Robertsonian translocation and insertion. Group C had the highest frequency in reciprocal translocation, inversion and insertion among the chromosomal groups. The highest balanced translocation prevalence was related to three chromosomes 9,3, and1. 9q12,1p36,3p11 were the most frequent breakpoints among them. Chromosome 9 had the largest contribution to inversions,22 to reciprocal translocations and14 to Robertsonian translocations. In the Robertsonian translocation, group D showed the highest frequency. Interestingly, patients carrying normal variations such as pericentric inversion of chromosome 9showed a significant alteration in sperm parameters, therefore normal variations showed a possible relationship to infertility. Limitations, reasons for caution In order to achieve stronger statistical results on DFI, a larger sample size would be more helpful. Wider implications of the findings The results may be useful to identify the most common breakpoints and consequently genes related to male infertility and can suggest appropriate molecular mechanism for their infertility. Trial registration number not applicable

A Threshold Voltage Definition Based on a Standardized Charge Versus Voltage Relationship

Threshold voltage defined by a band bending of twice the substrate intrinsic-to-Fermi level difference has been widely accepted. However, there are shortcomings with this analytical definition. Since the inversion condition is governed by the substrate Fermi level (i.e., majority carrier density per volume), inversion carrier density per area at threshold inadequately depends on substrate doping and temperature. Another problem is that the definition is not applicable to fully depleted thin body devices, such as FinFETs and silicon-on-insulator FETs, widely used today. To solve these problems, a new definition of threshold voltage is proposed, which is based on a standardized charge versus voltage relationship of ideal metal-oxide-semiconductor capacitors. Threshold voltage is specified by a threshold inversion carrier density per area, which is a simple function of gate oxide capacitance and thermal voltage. Dependence of the proposed threshold voltage on substrate doping, body thickness, and temperature for both bulk and double-gate FETs is discussed using semi-classical analytical equations.

Pericentric inversion of chromosome 6 and male fertility problems.

As a significant chromosomal structural abnormality, chromosomal inversion is closely related to male infertility. For inversion carriers, the interchromosomal effect explains male infertility, but its specific mechanism remains unclear. Additionally, inversion carriers with different chromosomes have different clinical manifestations. Therefore, genetic counseling is difficult in clinical practice. Herein, four male carriers of pericentric inversion in chromosome 6 have been described. Two patients showed asthenospermia, one showed azoospermia, and the wife of the remaining patient had recurrent miscarriages. Through a literature search, the association between the breakpoint of pericentric inversion in chromosome 6 and male fertility problems are also discussed in this study. Overall, important genes related to asthenospermia in chromosome 6p21 were found, which may be related to the clinical phenotype. These results suggest that physicians should focus on the breakpoints of inversion in genetic counseling.

Bias dependent physics-based model of low-frequency noise for nanowire type gate-all-around MOSFETs

In this study, the bias dependence of low-frequency noise (LFN) in nanowire type gate-all-around (GAA) MOSFETs was physically modeled. In the model, the inversion carrier density distribution was considered based on the potential in the channel that changes according to the bias. The developed model was verified with measurement data of the fabricated device. The model could help circuit designers to optimize noise performance in analog/RF applications when designing integrated circuits using nanowire-type GAA MOSFETs.

A mathematical model for predicting the number of transferable blastocysts in next-generation sequencing-based preimplantation genetic testing.

To investigate the clinical factors that could be used predict the number of transferable blastocysts in preimplantation genetic testing (PGT) cycles based on next-generation sequencing (NGS) and formed form a mathematical model to predict the chance likelihood of obtaining one transferable blastocyst, which is helpful for genetic counseling. This retrospective study enrolled couples undergoing PGT cycles for chromosomal structural rearrangement (PGT-SR, n = 363, 202 with reciprocal translocation carriers, 131 with Robertsonian translocation carriers, 30 with inversion carriers), monogenic diseases (PGT-M, n = 47), and for Aneuploidies (PGT-A, n = 132) from January 2015 to October 2018. Stepwise multiple linear regression analysis was used to identify the factors relevant for obtaining at least one transferable blastocyst. The factors that predict the number of biopsied blastocysts were further analyzed. The transferable blastocyst rates were 29.94, 41.99, 49.09, 41.42, and 44.37% in the reciprocal translocation carrier, Robertsonian translocation carrier, inversion carrier, PGT-M, and PGT-A cycles, respectively. The number of transferable blastocysts in these cycles were 0.3004 × the number of biopsied blastocysts (NBB) - 0.0031, 0.4063 × NBB + 0.0460, 0.5762 × NBB - 0.3128, 0.3611 × NBB + 0.1910, and 0.4831 × NBB - 0.0970, respectively. Furthermore, the number of MII oocytes and female age were clinical predictors of NBB in reciprocal translocation and PGT-A couples, while the number of MII oocytes was the only clinical predictor in Robertsonian translocation carriers, inversion carriers, and PGT-M couples. The number of biopsied blastocysts was the only clinical predictor of the ability to obtain a transferable blastocyst in PGT cycles; therefore, for clinical practice, theoretically the minimum numbers of biopsied blastocysts is 4 in reciprocal translocation carrier and 3 in couples undergoing PGT for other reasons. The number of MII oocytes and female age were clinical predictors of the number of biopsied blastocysts. With the mathematical models in our study as a reference, in clinical practice, clinicians will be able to conduct a more targeted genetic consultation for different kinds of PGT patients.

EP365 - PRKX/PRKY-mediated Xp;Yp translocations: a significant contributor to SRY-positive 46,XX TDSD and potential risk of recurrence in common Yp inversion carriers

eP365 - PRKX/PRKY-mediated Xp;Yp translocations: a significant contributor to SRY-positive 46,XX TDSD and potential risk of recurrence in common Yp inversion carriers

Capacitance Analysis of Transient Behavior Improved Metal-Insulator-Semiconductor Tunnel Diodes With Ultra Thin Metal Surrounded Gate

The metal-insulator-semiconductor tunnel diodes with ultra thin metal surrounded gate (UTMSG) have been found to have improved transient current behaviour, and the improvement is proportional to the area of the surrounding gate. The resistance induced by the thin metal gate leads to delay of inversion carriers under the surrounding gate. At the same time, the UTMSG devices could read the capacitance under the surrounding gate only in inversion regime, but not in accumulation and depletion regime. This could be explained by a proposed small signal circuit model. The large resistance within the metal gate blocks the AC signal coming from the surrounding gate. On the other hand, the increased inversion carrier density introduces an inversion channel, which will let the AC signal pass through. The successful reproduction of the experimental observed unusual capacitance-voltage characteristics by TCAD simulation proves the proposed model as well. Detailed simulations are implemented by varying different parameters to give a further understanding of the UTMSG device. A rough estimation of the resistance of the inversion channel is also given. The calculation shows the consistency with the proposed small signal circuit model. The UTMSG device could experience a larger change of magnitude of capacitance and hence a larger capacitance window when switching from 1 V to -0.3 V, verified by simulation. The simulation has also shown that the edge thickened oxide will only slightly modulate the capacitance of the UTMSG devices.

Functional differences in the hypothalamic-pituitary-gonadal axis are associated with alternative reproductive tactics based on an inversion polymorphism

The evolution of social behavior depends on genetic changes, yet, how genomic variation manifests itself in behavioral diversity is still largely unresolved. Chromosomal inversions can play a pivotal role in producing distinct behavioral phenotypes, in particular, when inversion genes are functionally associated with hormone synthesis and signaling. Male ruffs exhibit alternative reproductive tactics (ARTs) with an autosomal inversion determining two alternative morphs with clear behavioral and hormonal differences from the ancestral morph. We investigated hormonal and transcriptomic differences in the pituitary and gonads. Using a GnRH challenge, we found that the ability to synthesize testosterone in inversion carriers is severely constrained, whereas the synthesis of androstenedione, a testosterone precursor, is not. Inversion morphs were able to produce a transient increase in androstenedione following the GnRH injection, supporting the view that pituitary sensitivity to GnRH is comparable to that of the ancestral morph. We then performed gene expression analyses in a second set of untreated birds and found no evidence of alterations to pituitary sensitivity, gonadotropin production or gonad sensitivity to luteinizing hormone or follicle-stimulating hormone across morphs. Inversion morphs also showed reduced progesterone receptor expression in the pituitary. Strikingly, in the gonads, inversion morphs over-expressed STAR, a gene that is located outside of the inversion and responsible for providing the cholesterol substrate required for the synthesis of sex hormones. In conclusion, our results suggest that the gonads determine morph-specific differences in hormonal regulation.

Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population

BackgroundChromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion.MethodsA total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed.ResultsThere were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256).ConclusionsDue to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

Investigation of the interchromosomal effects in male carriers with structural chromosomal abnormalities using FISH.

The interchromosomal effect (ICE) refers to the uncertainty during meiosis where the rearrangement of the chromosomes affects the segregation of the chromosomes that are not involved in the structural chromosomal abnormalities. The aim of this study is to investigate the existence of ICE in the sperm nuclei of the males who have structural chromosomal abnormalities. Nine male individuals who are the carriers of the structural chromosomal abnormalities (patient group) and 14 male individuals who did not have any chromosomal abnormalities (control group) were diagnosed by the classical cytogenetic analysis. The aneuploidy of chromosomes 2, 3, 12, 13, 17, 18, 21, X, and Y in the sperm nuclei was investigated using the fluorescence in situ hybridization (FISH) method in these individuals. The patient group included 5 Robertsonian translocation (ROB) carriers, 3 reciprocal translocation (RCP) carriers, and 1 inversion carrier. A total of 51921 sperm nuclei were analyzed (19484 from the patient group and 32437 from the control group). While ICE was determined in 4 of 5 patients who were the carriers of ROB and an inversion carrier patient, it was not determined in the patient carrier of RCP. Our results suggest that there is ICE in the male carriers with a structural chromosomal abnormality, which appears to be translocation, breakpoint, chromosome, and patient dependent.

Генетический репродуктивный риск у носителей перицентрических инверсий

Перицентрические инверсии (ПИ) - это сбалансированные структурные хромосомные перестройки, частота которых в популяции варьирует от 0,12% до 0,7% [1]. Особенностью синапсиса и рекомбинации ПИ в мейозе является формирование инверсионной петли, единичный кроссинговер в которой может приводить к образованию рекомбинантных хромосом c дупликацией/делецией дистального по отношению к инверсии сегмента короткого плеча и делецией/дупликацией дистального сегмента длинного плеча соответственно. Клиническая значимость ПИ определяется риском формирования у носителя гамет (зигот) с хромосомным дисбалансом (ХД), приводящим к раннему спонтанному прерыванию беременности, мертворождению или рождению детей с пороками и/или аномалиями развития. Проведена оценка эмпирической частоты формирования сперматозоидов с рекомбинантными хромосомами, а также риска формирования гамет и выживаемости потенциальных зигот с ХД у четырех мужчин-носителей ПИ. Pericentric inversion are intrachromosomal balanced structural abnormalities. The frequency in the general population is ranged from about 0.12% to 0.7% [1]. To provide complete synapsis and recombination during meiosis pairing of the normal and inverted chromosomes requires the formation of inversion loop. One crossover within the inversion loop leads to the production of two complementary recombinant chromosomes with both duplicated and deleted chromosome segments including the regions distal to the inversion. The particular clinical relevance of inversion chromosomes is that they can set the stage for the generation of recombinant gametes that may lead to early miscarriages, stillbirth or congenital abnormalities. The estimation of empiric frequencies of recombinant spermatozoa, risk of abnormal gamete formation and potential zygote viability in four pericentric inversion carriers was performed.