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Objective: Noninvasive prenatal testing (NIPT) has been introduced in prenatal genetics, recently. Even though it is connected with biological, technical, medical and ethical issues also reviewed here, it is meanwhile applied as a standard screening test. One of the obvious, but yet not further reviewed peculiarities of NIPT is that the reported false positives rates are variant, specifically in European, compared with Chinese publications. Materials and methods: Here the only 15 suited studies on >600,000 cases were identified in which at least average pregnancy age was reported for the time NIPT was done. Results and conclusion: It could be shown, that NIPT is done in China in later weeks of gestation, than in other countries. Besides, here for the first time it is highlighted that false positive NIPT results are less frequent, the earlier the screening is performed. Most likely this is related to two biological phenomena: loss of trisomic pregnancies and preferential survival of fetuses which underwent trisomic rescue, however, with major trisomic populations in placenta. This yet not considered aspect needs to be kept in mind especially in late stage high risk pregnancies.

Abstract Chromosomal heteromorphisms (CHs) are morphological variations predominantly found in constitutive heterochromatic regions of the genome, primarily composed of tandemly repetitive sequences of satellite DNA. Although not completely devoid of genes, these regions are typically not transcribed into proteins and lack obvious phenotypic impact. Nonetheless, their clinical importance is increasingly under scrutiny, with several studies aiming to assess their influence on human diseases and susceptibilities, especially as they are seemingly part of the long noncoding RNAs in certain tissues. This article summarizes the classification methods of human heterochromatic CHs documented in the literature over the last two decades. Multiple scoring systems have been identified, and previous approaches for CH assessment and reporting in genetic diagnosis have shown inconsistencies. Owing to the current heterogeneity in the classification of CHs, data analysis may be biased, impacting the quality of clinical reports and human genetic research. This review highlights the need for a universal scoring system, which is essential for scientific reproducibility and the accurate identification and clinical evaluation of human CHs.

Abstract Do all birds' sex chromosomes follow the same canonical one-way direction of evolution? We combined cytogenetic and genomic approaches to analyze the process of the W chromosomal differentiation in two selected Passeriform species, named the Pale-breasted Thrush Turdus leucomelas and the Rufous-bellied thrush T. rufiventris. We characterized the full catalog of satellite DNAs (satellitome) of T. leucomelas, and the 10 TleSatDNA classes obtained together with 16 microsatellite motifs were in situ mapped in both species. Additionally, using Comparative Genomic Hybridization (CGH) assays, we investigated their intragenomic variations. The W chromosomes of both species did not accumulate higher amounts of both heterochromatin and repetitive sequences. However, while T. leucomelas showed a heterochromatin-poor W chromosome with a very complex evolutionary history, T. rufiventris showed a small and partially heterochromatic W chromosome that represents a differentiated version of its original autosomal complement (Z chromosome). The combined approach of CGH and sequential satDNA mapping suggest the occurrence of a former W-autosomal translocation event in T. leucomelas, which had an impact on the W chromosome in terms of sequence gains and losses. At the same time, an autosome, which is present in both males and females in a polymorphic state, lost sequences and integrated previously W-specific ones. This putative W-autosomal translocation, however, did not result in the emergence of a multiple-sex chromosome system. Instead, the generation of a neo-W chromosome suggests an unexpected evolutionary trajectory that deviates from the standard canonical model of sex chromosome evolution.

Abstract Multiple sex chromosomes usually arise from chromosomal rearrangements which involve ancestral sex chromosomes. There is a fundamental condition to be met for their long-term fixation: the meiosis must function, leading to the stability of the emerged system, mainly concerning the segregation of the sex multivalent. Here, we sought to analyze the degree of differentiation and meiotic pairing properties in the selected fish multiple sex chromosome system present in the wolf-fish Hoplias malabaricus (HMA). This species complex encompasses seven known karyotype forms (karyomorphs) where the karyomorph C (HMA-C) exhibits a nascent XY sex chromosomes from which the multiple X1X2Y system evolved in karyomorph HMA-D via a Y-autosome fusion. We combined genomic and cytogenetic approaches to analyze the satellite DNA (satDNA) content in the genome of HMA-D karyomorph and to investigate its potential contribution to X1X2Y sex chromosome differentiation. We revealed 56 satDNA monomers of which the majority was AT-rich and with repeat units longer than 100 bp. Seven out of 18 satDNA families chosen for chromosomal mapping by fluorescence in situ hybridization (FISH) formed detectable accumulation in at least one of the three sex chromosomes (X1, X2 and neo-Y). Nine satDNA monomers showed only two hybridization signals limited to HMA-D autosomes, and the two remaining ones provided no visible FISH signals. Out of seven satDNAs located on the HMA-D sex chromosomes, five mapped also to XY chromosomes of HMA-C. We showed that after the autosome-Y fusion event, the neo-Y chromosome has not substantially accumulated or eliminated satDNA sequences except for minor changes in the centromere-proximal region. Finally, based on the obtained FISHpatterns, we speculate on the possible contribution of satDNA to sex trivalent pairing and segregation.

Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent pediatric leukemia; it can be defined according to chromosomic and genomic data. Cytogenetic analyses and determination of chromosomal numbers (such as hypo- or hyperdiploidy) and/or specific chromosomal rearrangements are basic for ALL classification and treatment. Even though cure rates of childhood ALL are at ~95%, pharmacogenetic aspects are of raising importance. Material and Methods: We have analyzed the literature for ALL subtypes, corresponding therapy options, and pharmacogenetic implications. Results: Data for ALL subtypes such as B-ALL, T-ALL, Ph-like ALL, DS-ALL, ETP-ALL, BCR-ABL1-like ALL are presented here. The gene polymorphism which lead to metabolizability of 6-MP are ITPA variants (94C>A) and IVS2+21A>C, in conjunction with TPMT (238G>C, TPMT*3B 460G>A and *3C 719A>G and NUDT15 (415C>T). For methotrexate metabolism gene polymorphisms are found for gene MTHFR as C677T and A1298C. Conclusion: In the last decade in many hospital laboratories, pharmacogenetic aspects gain more and more importance. Application of many molecular biology methods provided progress in treatment and diagnosis of ALL patients. Combination therapy is proposed as an alternative to single drug treatments.

Abstract Background Different patterns of sex chromosome differentiation are seen in Palaeognathae birds, a lineage that includes the ratites (Struthioniformes, Rheiformes, Apterygiformes, Casuariiformes, and the sister group Tinamiformes). While some Tinamiform species have well-differentiated W chromosomes, both Z and W of all the flightless ratites are still morphologically undifferentiated. Here, we conducted a comprehensive analysis of the ZW differentiation in birds using a combination of cytogenetic, genomic, and bioinformatic approaches. The whole set of satDNAs from the emu (Dromaius novaehollandiae) was described and characterized. Furthermore, we examined the in situ locations of these satDNAs alongside several microsatellite repeats and carried out Comparative Genomic Hybridizations in two related species: the greater rhea (Rhea americana) and the tataupa tinamou (Crypturellus tataupa). Results From the 24 satDNA families identified (which represent the greatest diversity of satDNAs ever uncovered in any bird species), only three of them were found to accumulate on the emu’s sex chromosomes, with no discernible accumulation observed on the W chromosome. The W chromosomes of both the greater rhea and the emu did not exhibit a significant buildup of either C-positive heterochromatin or repetitive DNAs, indicating their large undifferentiation both at morphological and molecular levels. In contrast, the tataupa tinamou has a highly differentiated W chromosome that accumulates several DNA repeats. Conclusion The findings provide new information on the architecture of the avian genome and an inside look at the starting points of sex chromosome differentiation in birds.

ABSTRACTGoat raising has increased in Lao People’s Democratic Republic due to meat demand from Vietnam. Goat production is low input using free grazing and minimal husbandry. Technical constraints are well known but socio-cultural contexts are poorly understood. This paper describes qualitative research on farmer’s motivations, experiences and learning pathways, to improve goat husbandry. Semi-structured interviews were conducted with 30 smallholder goat farmers in Lao’s South-Central province of Savannakhet. The interviews revealed that farmers relied on their experiences and observations of goat raising in their communities to make their management decisions. Trial and error was a valued learning strategy. Farmers took guidance from the exchange of goat raising experiences with other goat farmers and preferred participatory learning that fostered discussion in familiar village settings. Lao smallholder goat farming systems are a product of compromise across a number of resources. Project interventions that required low investments of labour, land or capital were most readily implemented and adapted by farmers. This study questions the assumption that project interventions are inherently optimal and beneficial for smallholder farming systems. Recommendations propose how farmer’s experiences, constraints and preferences can be incorporated into development approaches to ensure management system changes reflect the desires of smallholder farmers.

Resistive Random-Access Memory (RRAM) presents a transformative technology for diverse computing and artificial intelligence applications. However, variability in the high resistance state (HRS) has proved to be a challenge, impeding its widespread adoption. This study focuses on optimizing TaOx-based RRAMs by strategically placing a nitrogen-doped TaOx barrier-layer (BL) to mitigate variability in the HRS. Through comprehensive electrical characterization and measurements, we uncover the critical influence of BL positioning on HRS variability and identify the optimal location of the BL to achieve a 2x lowering of HRS variability as well as an expanded range of operating voltages. Incremental reset pulse amplitude measurements show that the TaOx:N maintains a low HRS variability even at higher operating voltages when the position of the BL is optimized. Our findings offer insights into stable and reliable RRAM operation, highlighting the potential of the proposed BL to enhance the functionality of TaOx-based RRAMs and elevate overall device performance.

Abstract Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.

Abstract Background Crocodilians are one of the oldest extant vertebrate lineages, exhibiting a combination of evolutionary success and morphological resilience that has persisted throughout the history of life on Earth. This ability to endure over such a long geological time span is of great evolutionary importance. Here, we have utilized the combination of genomic and chromosomal data to identify and compare the full catalogs of satellite DNA families (satDNAs, i.e., the satellitomes) of 5 out of the 8 extant Alligatoridae species. As crocodilian genomes reveal ancestral patterns of evolution, by employing this multispecies data collection, we can investigate and assess how satDNA families evolve over time. Results Alligators and caimans displayed a small number of satDNA families, ranging from 3 to 13 satDNAs in A. sinensis and C. latirostris, respectively. Together with little variation both within and between species it highlighted long-term conservation of satDNA elements throughout evolution. Furthermore, we traced the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatorinae. Fluorescence in situ experiments showed distinct hybridization patterns for identical orthologous satDNAs, indicating their dynamic genomic placement. Conclusions Alligators and caimans possess one of the smallest satDNA libraries ever reported, comprising only four sets of satDNAs that are shared by all species. Besides, our findings indicated limited intraspecific variation in satellite DNA, suggesting that the majority of new satellite sequences likely evolved from pre-existing ones.

The ability of the SARS-CoV-2 virus to cause DNA damage in infected humans requires its study as a potential indicator of COVID-19 progression. DNA damage was studied in leukocytes of 65 COVID-19 patients stratified by sex, age, and disease severity in relation to demographic, clinical, and laboratory parameters. In a combined group of COVID-19 patients, DNA damage was shown to be elevated compared to controls (12.44% vs. 5.09%, p < 0.05). Severe cases showed higher DNA damage than moderate cases (14.66% vs. 10.65%, p < 0.05), and males displayed more damage than females (13.45% vs. 8.15%, p < 0.05). DNA damage is also correlated with international normalized ratio (INR) (r = 0.471, p < 0.001) and creatinine (r = 0.326, p < 0.05). In addition to DNA damage, severe COVID-19 is associated with age, C-reactive protein (CRP), and creatinine. Receiver operating characteristic analysis identified age, INR, creatinine, DNA damage, and CRP as significant predictors of disease severity, with cut-off values of 72.50 years, 1.46 s, 78.0 µmol/L, 9.72%, and 50.0 mg/L, respectively. The results show that DNA damage correlates with commonly accepted COVID-19 risk factors. These findings underscore the potential of DNA damage as a biomarker for COVID-19 severity, suggesting its inclusion in prognostic assessments to facilitate early intervention and improve patient outcomes.