Additional Chromosome Research Articles

Characterization of aneuploidy in interspecific hybrid between Urochloa ruziziensis (R. Germ. & Evrard) Crins and Urochloa decumbens (Stapf) R. D. Webster.

The aim of the study was to characterize the type of aneuploidy present in the hybrid Urochloa ruziziensis×Urochloa decumbens and to confirm the origin of the additional chromosomes through comparative analysis of the hybrid and parental karyotypes. C andCMA bandingtechniques were used for chromosome differentiation. The parental genotypes showed 36 chromosomes. The hybrid presented plants with 36 + 2 chromosomes and plants with 36 + 1 chromosomes. Urochloa ruziziensis (4x) presented four chromosomes with CMA and C bands co-located in the terminal position. In U. decumbens, four chromosomes presented terminal CMA bands, eight chromosomes were distinguished by Cbanding with pericentromeric and terminal bands, one chromosome with terminal band at both ends and one chromosome presented one Cterminal band. For the hybrid, CMA bands were found on five chromosomes and C bands on seven chromosomes, all in terminal position. Aneuploidy was identified in pairs 3' and 4' in the hybrid plants with 36 + 2 chromosomes, characterizing it as double trisomy. The karyotype of hybrid plants with 36 + 1 chromosomes indicated elimination of the additional chromosome identified in pair 4' and maintenance of trisomy on pair 3'. The comparative analysis of karyotypes indicates that the additional chromosomes that characterize the trisomy were inherited from U. ruziziensis (artificial tetraploid).

Isolating Chromosomes of the Komodo Dragon: New Tools for Comparative Mapping and Sequence Assembly

We developed new tools to build a high-quality chromosomal map of the Komodo dragon (Varanus komodoensis) available for cross-species phylogenomic analyses. First, we isolated chromosomes by flow sorting and determined the chromosome content of each flow karyotype peak by FISH. We then isolated additional Komodo dragon chromosomes by microdissection and amplified chromosome-specific DNA pools. The chromosome-specific DNA pools can be sequenced, assembled, and mapped by next-generation sequencing technology. The chromosome-specific paint probes can be used to investigate karyotype evolution through cross-species chromosome painting. Overall, the set of chromosome-specific DNA pools of V. komodoensis provides new tools for detailed phylogenomic analyses of Varanidae and squamates in general.

Characterization of Chromosomal Rearrangement in New Wheat—Thinopyrum intermedium Addition Lines Carrying Thinopyrum—Specific Grain Hardness Genes

The wild species, Thinopyrum intermedium. (Genome StStJSJSJJ), serves as a valuable germplasm resource providing novel genes for wheat improvement. In the current study, non-denaturing fluorescence in situ hybridization (ND-FISH) with multiple probes and comparative molecular markers were applied to characterize two wheat-Th. intermedium chromosome additions. Sequential ND-FISH with new labeled Th. intermedium specific oligo-probes were used to precisely determine the chromosomal constitution of Th. intermedium, wheat—Th. intermedium partial amphiploids and addition lines Hy36 and Hy37. The ND-FISH results showed that the added JS-St translocated chromosomes in Hy36 had minor Oligo-5S ribosomal DNA (rDNA) signals at the short arm, while a pair of J-St chromosomes in Hy37 had major Oligo-pTa71 and minor Oligo-5S rDNA signals. The 90K SNP array and PCR-based molecular markers that mapped on wheat linkage group 5 and 3 facilitated the identification of Thinopyrum chromosome introgressions in the addition lines, and confirmed that added chromosomes in Hy36 and Hy37 were 5JSS.3StS and 5JS.3StS, respectively. Complete coding sequences at the paralogous puroindoline-a (Pina) loci from Th. intermedium were cloned and localized on the short arm of chromosome 5JS of Hy36. Line Hy36 showed a reduction in the hardness index, which suggested that Th. intermedium-specific Pina gene sequences may be associated with the softness trait in wheat background. The molecular cytogenetic identification of novel wheat—Th. intermedium derivatives indicated that the frequent chromosome rearrangement occurred in the progenies of wheat-Thinopyrum hybridization. The new wheat-Thinopyrum derived lines may increase the genetic diversity for wheat breeding.

Noninvasive screening by cell-free DNA for 22q11.2 deletion: Benefits, limitations, and challenges.

Cell-free DNA (cfDNA) testing for fetal aneuploidy is one of the most important technical advances in prenatal care. Additional chromosome targets beyond common aneuploidies, including the 22q11.2 microdeletion, are now available because of this clinical testing technology. While there are numerous potential benefits, 22q11.2 microdeletion screening using cfDNA testing also presents significant limitations and pitfalls. Practitioners who are offering this test should provide comprehensive pretest and posttest prenatal counselling. The discussion should include the possibility of an absence of a result, as well as the risk of possible discordance between cfDNA screening results and the actual fetal genetic chromosomal constitution. The goal of this review is to provide an overview of the cfDNA testing technologies for 22q11.2 microdeletions screening, describe the current state of test validation and clinical experience, review "no results" and discordant findings based on differing technologies, and discuss management options.

Achievements and Challenges in Allogeneic Hematopoietic Stem Cell Transplantation in Cytogenetically Unfavorable Acute Leukemias (Literature Review)

Literature review provides the analysis of treatment results of implementing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with cytogenetically unfavorable acute myeloid and lymphoblastic leukemias including monosomal, complex, and hyperdiploid karyotypes, t(3;3)/inv(3), t(v;11)(v;q23), t(4;11)(q21;q23), t(9;22)(q34;q11) translocations, 17p abnormalities, and some other disorders. The major disadvantage of allo-HSCT seems to be linked to a strong chromosome-damaging effect of cytostatic drugs used in conditioning regimens which in turn is associated with additional chromosome abnormalities occurring in tumors, increasing genomic instability, and tumor progression. On the other hand, one of the advantages of allo-HSCT can consist in its specific “graft versus leukemia” (GVL) effect whose degree has not yet been adequately studied. To minimize the risks of allo-HSCT in above mentioned patients it appears appropriate to apply new treatment approaches based on de-escalation of chromosome- and whole-genome-damaging effects and also to introduce recent methods of active stimulation and qualitative assessment of GVL effect into clinical practice.

The Association of Motor Skills and Adaptive Functioning in XXY/Klinefelter and XXYY Syndromes

Aims: Klinefelter (XXY) and XXYY syndromes are genetic disorders in males characterized by additional sex chromosomes compared to the typical male karyotype of 46, XY. Both conditions have been previously associated with motor delays and motor skills deficits. We aimed to describe and compare motor skills in males with XXY and XXYY syndromes, and to analyze associations with age, cognitive abilities, and adaptive functioning. Methods: Sixty-four males with XXY and 46 males with XXYY, ages 4–20 were evaluated using the Beery Test of Visual Motor Integration and the Bruininks-Oseretsky Test of Motor Proficiency – 2nd Edition assessments, Vineland–2 adaptive scales, and cognitive testing. Results: Motor coordination impairments were found in 39% of the males with XXY and 73% of the males with XXYY. Both groups showed strengths in visual perceptual skills. Males with XXYY had lower mean scores compared to males with XXY across all assessments. Fine motor dexterity and coordination deficits were common. There was a positive correlation between VMI scores and adaptive functioning. Conclusion: Occupational and physical therapists should be aware of the motor phenotype in XXY and XXYY both to aid in diagnosis of unidentified cases and to guide intervention.

Interspecies Hybridisation and Genome Chimerisation in Saccharomyces: Combining of Gene Pools of Species and Its Biotechnological Perspectives.

Over the last one and a half decade, interspecies hybridisation has gained continuously increasing attention as a breeding technique suitable for transferring of genetic information between Saccharomyces species and mixing of their gene pools without genetic engineering. The hybrids frequently show positive transgressive phenotypes. Segregation of the hybrid genome results in mosaic (chimeric) strains that can outperform both the parents and the hybrids or exhibit novel positive phenotypic properties. Mitotic segregation can take place during the vegetative propagation of the sterile allodiploid hybrid cells. Meiotic segregation becomes possible after genome duplication (tetraploidisation) if it is followed by break-down of sterility. The allotetraploid cells are seemingly fertile because they form viable spores. But because of the autodiploidisation of the meiosis, sterile allodiploid spores are produced and thus the hybrid genome does not segregate (the second sterility barrier). However, malsegregation of MAT-carrying chromosomes in one of the subgenomes during allotetraploid meiosis (loss of MAT heterozygosity) results in fertile alloaneuploid spores. The breakdown of (the second) sterility barrier is followed by the loss of additional chromosomes in rapid succession and recombination between the subgenomes. The process (genome autoreduction in meiosis or GARMe) chimerises the genome and generates strains with chimeric (mosaic) genomes composed of various combinations of the genes of the parental strains. Since one of the subgenomes is preferentially reduced, the outcome is usually a strain having an (almost) complete genome from one parent and only a few genes or mosaics from the genome of the other parent. The fertility of the spores produced during GARMe provides possibilities also for introgressive backcrossing with one or the other parental strain, but genome chimerisation and gene transfer through series of backcrosses always with the same parent is likely to be less efficient than through meiotic or mitotic genome autoreduction. Hybridisation and the evolution of the hybrid genome (resizing and chimerisation) have been exploited in the improvement of industrial strains and applied to the breeding of new strains for specific purposes. Lists of successful projects are shown and certain major trends are discussed.

Clinical Significance of Additional Chromosomal 8 Clonal Evolution in CML Progression

To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression. An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported. This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period. These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.

The Combination of Complex Karyotypes' Subtypes and IGHV Mutational Status Provides Prognostic and Predictive Information in Chronic Lymphocytic Leukemia

INTRODUCTION. Complex karyotype (CK), defined by the presence of at least 3 chromosomal abnormalities, is a heterogeneous cytogenetic category associated with adverse prognosis in several hematologic malignancies. Recently, Rigolin et al. provided evidence that CK with major structural abnormalities (CK2) at chronic lymphocytic leukemia (CLL) diagnosis negatively impact on the time to first treatment (TTFT) and overall survival (OS) (Rigolin GM, BJH 2018). However, it is unknown whether the prognostic strength of CK could be implemented when combined with stable markers such as the IGHV mutational status. In the present study, we assessed the prognostic and predictive role of the combination of CK subtypes and IGHV status in a large CLL series.METHODS. Stimulated cytogenetics with CpG+IL2 was performed in 736 CLL patients in 3 referenced Italian hematological centers. According to Rigolin et al, CK2 cases included unbalanced translocations, addition, insertion, derivative and marker chromosomes. All other CK were classified as type 1 (CK1). An IGHV gene sequence homology >98% was considered as unmutated (U-IGHV), as opposed to mutated (M-IGHV). Treatment was initiated according to the iwCLL guidelines. TTFT and OS were calculated from diagnosis to first treatment or death, respectively, or last known follow-up. Survival curves were compared with the log-rank test and p<.05 was considered as significant. Harrell concordance index (c-index) was used to compare our prognostic model with Dohner's and FISH-IGHV models.RESULTS. We focused on 520 out of the 736 patients with cytogenetic and IGHV status assessed within 12 months from diagnosis. The median age at diagnosis was 63 years, 322 (62%) were males, 68% at Binet A stage, 45% U-IGHV, 48 harbored TP53 abnormalities, 99 a CK (28 CK1 and 71 CK2), 232 received at least one line of therapy (31% FCR, 16% BR, 8% ibrutinib, 5% chlorambucil-antiCD20, 40% other treatments) and 80 died over a median follow-up of 5.8 years.71 (14%) harbored CK2, 214 (41%) CK1 or U-IGHV and 235 (45%) M-IGHV without CK2. The former group were characterized by a higher prevalence TP53 (38% vs 8% vs 3%, p<0.0001) and cytogenetics abnormalities but lower cases with low-risk FISH (i.e. 13q or normal; 38% vs 54% vs 91%, p<0.0001) as compared with others two groups. We observed that subjects with CK2 had a shorter TTFT (median years 1.97, 3.40 and 19.1, p<0.0001) and 5 years OS (67%, 85%, 93%, p<0.0001) compared to cases with CK1/U-IGHV, or M-IGHV without CK. These data were confirmed in multivariate analysis. The worse prognosis of CK2 patients was independent of TP53 status (p values 0.0770 and 0.8122 for TTFT and OS, respectively). The c-indexes for our model were 69% and 68% for TTFT and OS, respectively, and were not inferior to those calculated with Dohner's (64% and 61%) and FISH-IGHV (69% and 63%) models.The combination of these two markers also provides predictive information after first-line therapy (p<0.0001 for both TTFT and OS). In particular, among 107 patients treated with FCR or BR just one of the M-IGHV cases relapsed but none died after a median follow-up of 43 months as compared with the other two subgroups (3-year PFS 92%, 69% and 23%, p<0.0001; 3-year OS: 100%, 94%, 62%, p<0.0001).CONCLUSIONS. In this study, we demonstrated that the combination of CK subtypes and IGHV status provides important prognostic and predictive data in CLL. Moreover, our model was not inferior to other commonly used prognostic scores. While patients with M-IGHV without any subtypes of CK showed an excellent outcome with chemoimmunotherapy, new alternative therapies should be explored for patients with CK2. DisclosuresVisentin:janssen: Consultancy, Honoraria. Rigolin:Gilead: Research Funding. Mauro:abbvie: Other: board member; janssen: Other: board member. Foà:JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau; INCYTE: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau. Cuneo:Roche: Other: advisory board, Speakers Bureau; Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau. Trentin:Gilead: Research Funding; Janssen: Research Funding; Abbvie: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.

International, Prospective Study Comparing Nilotinib Versus Imatinib with Early Switch to Nilotinib to Obtain Sustained Treatment-Free Remission in Patients with Chronic Myeloid Leukemia. a GIMEMA and HOVON Study

BackgroundThe best front-line treatment of CML is not yet defined. Indeed, despite the higher activity of the second-generation TKIs respect to Imatinib and the higher rates of deep molecular remission (DMR), no clear superiority in term of long-term overall survival among the first and second TKIs for the initial treatment of CML has been shown in all the available studies. Furthermore, treatment free remission is emerging as one of the most important goal of the treatment of this disease, but no clinical trial has shown so far the best first line treatment to reach this aim.MethodsSince it is widely accepted that a sustained DMR is the pre-requisite to discontinue the TKI treatment for an extended duration of time, and since in patients who start treatment with imatinib (IM) and fail EMR, it is expected that a switch to NIL may improve the probability of achieving a DMR, we launched in November 2016 an international, prospective, interventional, randomized, two arms, phase IV study to evaluate both the depth of the molecular response and the rate of TFR in newly diagnosed CP-CML patients treated with a second generation TKI (Nilotinib, NIL) or with Imatinib (IM) followed by switch to NIL in absence of optimal response (defined according the ELN 2013 criteria (Clinical Trial number 02602314) The enrolled patients are randomized 1:1 between NIL and IM. Patients are stratified at randomization according to the Sokal risk score (high versus intermediate/low risk) and country (Italy, The Netherlands, Belgium). All the patients who obtain a reduction greater than 4.0 logs of residual disease (MR4.0) within the first three years of treatment, and maintain this level of response in all the subsequent tests up to the end of the fourth years of therapy qualify for the discontinuation phase of the study. The study has two primary end-points: a) the rates of molecular response (MR4.5) at 24 months, and b) the rate of patients who remain in sustained treatment free remission (≥MR3.0) without molecular relapse 12 months after entering the TFR phase. The molecular relapse is defined as loss of MMR, or confirmed loss of MR3.0. Differences in the patient-reported quality of life (QoL) were are investigated by QoL questionnaires (EORTC QLQ-C30 and EORTC CML-24) at baseline (before the randomization) and at 3, 6, 12, 18, 24, 30, 36, 42, 48, 60 months. A total of 165 patients will be enrolled. Enrollment will be concluded in 2019, and final results will be given in 2024.ResultsFrom November 2016 to the 15 July 15 2018, 165 patients with newly diagnosed CP-CML patients (mean age 54.6 years - range 20.0-85.8) were enrolled and randomized into the two arms of the study. Of those, 137 (83%) were classified as low/intermediate-risk Sokal, and the remaining 28 (17%) as high-risk. Additional chromosome abnormalities in the Philadelphia positive clone were detected in 20 (12.1%) patients, 7 (8.5%) in the IM group and 13 (15.9%) in the NIL group.Overall, 12 patients of the IM group switched to NIL; for absence of optimal response at 3 months in two cases, at 6 months in 7 patients and at 12 months in one case. The remaining two patients switched to NIL for IM related toxicity. Among NIL treated patients, two patient stopped treatment, in one case at 1 month due to absence of hematological response and the other due to suboptimal response at 15 months. These patients were treated according to the principal investigator of the participating center and censored for final analysis.At a preliminary evaluation of patient-reported QoL questionnaires completed at baseline, women and elderly had a perception of higher symptom burden.ConclusionThis is the first and the unique prospective study comparing not only the rate of DMR but, more important, also the rate of TFR according to treatment: a second generation TKI frontline vs Imatinib frontline followed by the same second generation in case of non-optimal response to ImatinibAcknowledgmentsThe present study is a non-commercial study sponsored by Fondazione GIMEMA together with the HOVON that are responsible for the database of the study. Novartis Pharma supports the study with an unrestricted grant. DisclosuresPane:AMGEN: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau. Abruzzese:BMS: Consultancy; Ariad: Consultancy; Pfizer: Consultancy; Novartis: Research Funding. Breccia:Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Soverini:Incyte Biosciences: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Consultancy. Castagnetti:Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Janssen:Pfizer: Consultancy, Speakers Bureau; Novartis: Research Funding; Incyte: Consultancy, Speakers Bureau; BMS: Research Funding; Abbvie: Consultancy; Jazz pharmaceuticals: Consultancy.

Clinical and Molecular Heterogeneity of Moderate Aplastic Anemia

Clinical and Molecular Heterogeneity of Moderate Aplastic Anemia

Nitrogen and phosphorus use efficiency of 43 wheat alien chromosome addition lines evaluated by hydroponic culture

Wild relatives of wheat may possess useful traits or genes for efficient use of nitrogen (N) or phosphorus (P). Forty-three wheat addition lines with alien chromosomes from Leymus, Agropyron, Hordeum, Psathyrostachys, Aegilops, and Secale cereale, along with their common parent Chinese Spring (CS) were cultured by hydroponics, and their phenotypic variation, N/P uptake and utilization efficiency were investigated at seedling stage. The phenotypic variation showed that N deficiency decreased plant height, shoot dry weight, and total dry weight, while increased root length, number of leaves, SPAD value, and root to shoot ratio (R/S); while P deficiency decreased all the measured traits except root dry weight and R/S. Aegilops longissima 2S and Aegilops searsii 4SS addition lines were identified as both N- and P-efficient germplasm, of which Ae. longissima 2S addition line showed significant increased N and P uptake efficiency than CS under all treatments.

“Space” Pea Pisum sativum L. and Wheat Triticum compactum Host. Plants as Objects of Cytogenetic Studies

The peculiarities of meiosis, C-heterochromatin (C-HC) distribution, and the activity of nucleolus organizer regions (NORs) of the chromosomes were studied in the Pisum sativum L. pea and Triticum compactum Host. club wheat grown from the seeds obtained in Lada space greenhouse on the board of RS ISS. It was noted that the analysis of meiosis detected no significant violations in the “space” plant cells, and the total amount of C-HC did not differ significantly from the control, despite the polymorphism of the chromosome C-banding pattern. Paracentric inversion on the chromosome 4A was found for the first time in the T. compactum, while no additional active NOR chromosomes were found.

Assessment of different anther culture approaches to produce doubled haploids in cucumber (Cucumis sativus L.)

Cucumber is one of the most important vegetable crops worldwide, which makes it a good candidate to produce doubled haploid (DH) lines to accelerate plant breeding. Traditionally, these approaches involved induction of gynogenesis or parthenogenesis with irradiated pollen, which carries some disadvantages compared to androgenesis. Despite this, studies on anther/microspore cultures in cucumber are surprisingly scarce. Furthermore, most of them failed to unambiguously demonstrate the haploid origin of the individuals obtained. In this work we focused on anther cultures using two cucumber genotypes, different previously published protocols for anther culture, different in vitro culture variants to make it more efficient, and most importantly, a combination of flow cytometry and microsatellite molecular markers to evaluate the real androgenic potential and the impact of anther wall tissue proliferation. We developed a method to produce DH plants involving a bud pretreatment at 4 °C, a 35 °C treatment to anthers, culture with BAP and 2,4-D, and induction of callus morphogenesis by an additional 35 °C treatment and sequential culture first in liquid medium in darkness and second in solid medium with light. We also found that factors such as genotype, proliferation of anther wall tissues, orientation of anthers in the culture medium and growth regulator composition of the initial anther culture medium have a remarkable impact. Our rate of chromosome doubling (81%) was high enough to exclude additional chromosome doubling steps. Together, our results present androgenesis as an improvable but yet more convenient alternative to traditional gynogenesis and parthenogenesis-based approaches.

Novel molecular marker-assisted strategy for production of wheat\u2013Leymus mollis chromosome addition lines

Developing wheat–alien chromosome introgression lines to improve bread wheat’s resistance to stresses, such as drought, salinity stress and diseases, requires reliable markers to identify and characterize the alien chromatins. Leymus mollis is a wild relative of bread wheat resistant to salinity and economically important diseases of wheat, but its genome sequence and cytological markers are not available. We devised a molecular marker-assisted strategy for L. mollis chromosome identification and applied it to produce 10 wheat–L. mollis chromosome addition lines. Using 47 L. racemosus genome polymorphic PCR markers and DArTseq genotyping, we distinguished the L. mollis chromosomes and differentiated disomic and monosomic lines by progeny test. DArTseq genotyping generated 14,530 L. mollis SNP markers and the chromosome-specific SNP markers were used to determine the homoeologous groups of L. mollis chromosomes in the addition lines. To validate the marker-based results, genomic in situ hybridization was applied to confirm the presence and cytological status of L. mollis chromosomes in the lines. This study demonstrates that adequate molecular markers allow the production and characterization of wheat–alien addition lines without in situ hybridization, which saves considerable time and effort.

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis.

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.2.

Resistance of (Aegilops tauschii × Secale cereale) × Triticosecale Hybrids to Leaf Rust (Puccinia triticina) Determined on the Macroscopic and Microscopic Level.

Leaf rust caused by Puccinia triticina Eriks belongs to the most important fungal pathogens of wheat (Triticum aestivum L.) and triticale (× Triticosecale). Effective resistance to leaf rust is both, cost-effective and environmentally safe. Many wild Aegilops species carry unknown resistances against fungal diseases and are characterized by a high genetic variability. The main goal of this work was to examine the resistance of (Aegilops tauschii × Secale cereale) × Triticosecale hybrids to leaf rust in inoculation tests with different races of P. triticina. Hybrid plants were selected for the presence of 2D chromosome/s in the triticale background using fluorescence and genomic in situ hybridization. The presence of leaf rust resistance genes was confirmed with closely linked molecular markers, i.e., Xgdm35 and Xgwm296. 14 genotypes of BC2F4 – BC2F6 hybrid plants with the monosomic addition of chromosome 2D (M2DA) were analyzed together with nine control lines. Resistance was determined at the macroscopic and microscopic level at the seedling and adult plant stage (flag leaf). In general, results revealed limited resistance of hybrid plants at the seedling stage, followed by an increase of the resistance level at later stages of plant development. This indicates that respective hybrid plants may exhibit APR resistance conferred by Lr22a introgressed from Ae. tauschii. On the basis of the macroscopic and microscopic analysis, this kind of resistance turned out to be additive and race-specific. We selected four monosomic 2D addition triticale genotypes highly resistant to P. triticina infection at the two main stages of plant development. From the selected genotypes, we obtained 26 doubled haploid lines among which two lines with doubled additional chromosomes 2D of Ae. tauschii can be used for further breeding to increase leaf rust resistance of cultivated triticale.

The novel three-way variant t(6;17;15)(p21;q21;q22) in acute promyelocytic leukemia with an FLT3-ITD mutation: A case report.

Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17)(q22;q21), resulting in the fusion of the promyelocytic leukemia gene at 15q22 with the retinoic acid receptor α at 17q21. Additionally, all patients with APL who have additional chromosome abnormalities (ACA) and gene mutations are resistant to all-trans retinoic acid (ATRA), the drug that causes disease regression specifically in patients with APL globally. The present study describes a case of a 19-year-old female with APL carrying a novel complex variant translocation t(6;17;15)(p21;q21;q22), add(7)(q32) and an FMS-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation. Complete remission was attained following a course of chemotherapy with ATRA and arsenic trioxide. To the best of our knowledge, this is the first report of a novel three-way translocation of 6p21 and a FLT3-ITD mutation involved with APL.

Report of new case of Pallister – Killian syndrome in fetus

Pallister — Killian syndrome (PKS) is a sporadic chromosomal anomaly caused by a tissue-specific mosaic distribution of an additional isochromosome 12p. A case of second trimester fetus with PKS is presented. Antenatal ultrasound examination showed left diaphragmatic hernia. Standard cytogenetic analysis of cultured amniocytes supposed mosaic tetrasomy 12p: 46,XY/ 47,XY,+?i(12p). Fluorescent in situ hybridization (FISH) was used to confirm the nature of the additional chromosome. Pathological examination confirmed prenatal diagnosis.

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.2