Hemivertebra is a rare congenital abnormality of the spinal column. Hemivertebra with other structural and cytogenetic abnormalities are reported. The prognosis is favorable with partial hemivertebra and with a single spinal defect as compared to a defect involving full segments and affecting different levels of the spines. The perinatal outcome is obscured when it is associated with other syndromes or cytogenetic abnormality. It is imperative to do serial thorough anatomical ultrasound scanning and to screen for chromosomal abnormality when hemivertebra is detected during pregnancy.

Alternative oxidase is a terminal oxidase in the branched mitochondrial electron transport chain of most fungi including Aspergillus niger (subgenus Circumdati, section Nigri). A second, paralogous aox gene (aoxB) is extant in some A. niger isolates but also present in two divergent species of the subgenus Nidulantes-A. calidoustus and A. implicatus-as well as in Penicillium swiecickii. Black aspergilli are cosmopolitan opportunistic fungi that can cause diverse mycoses and acute aspergillosis in immunocompromised individuals. Amongst the approximately 75 genome-sequenced A. niger strains, aoxB features considerable sequence variation. Five mutations were identified that rationally affect transcription or function or terminally modify the gene product. One mutant allele that occurs in CBS 513.88 and A. niger neotype strain CBS 554.65 involves a chromosomal deletion that removes exon 1 and intron 1 from aoxB. Another aoxB allele results from retrotransposon integration. Three other alleles result from point mutations: a missense mutation of the start codon, a frameshift, and a nonsense mutation. A. niger strain ATCC 1015 has a full-length aoxB gene. The A. niger sensu stricto complex can thus be subdivided into six taxa according to extant aoxB allele, which may facilitate rapid and accurate identification of individual species.

BACKGROUND: In plant genome editing, RNA-guided nucleases such as Cas9 from Streptococcus pyogenes (SpCas9) predominantly induce small insertions or deletions at target sites. This can be used for inactivation of protein-coding genes by frame shift mutations. However, in some cases, it may be advantageous to delete larger chromosomal segments. This is achieved by simultaneously inducing double strand breaks upstream and downstream of the segment to be deleted. Experimental approaches for the deletion of larger chromosomal segments have not been systematically evaluated.
RESULTS: We designed three pairs of guide RNAs for deletion of a ~ 2.2 kb chromosomal segment containing the Arabidopsis WRKY30 locus. We tested how the combination of guide RNA pairs and co-expression of the exonuclease TREX2 affect the frequency of wrky30 deletions in editing experiments. Our data demonstrate that compared to one pair of guide RNAs, two pairs increase the frequency of chromosomal deletions. The exonuclease TREX2 enhanced mutation frequency at individual target sites and shifted the mutation profile towards larger deletions. However, TREX2 did not elevate the frequency of chromosomal segment deletions.
CONCLUSIONS: Multiplex editing with at least two pairs of guide RNAs (four guide RNAs in total) elevates the frequency of chromosomal segment deletions at least at the AtWRKY30 locus, and thus simplifies the selection of corresponding mutants. Co-expression of the TREX2 exonuclease can be used as a general strategy to increase editing efficiency in Arabidopsis without obvious negative effects.

The etiology of oculo-auriculo-vertebral spectrum (OAVS) is not well established. About half of patients show a positive family history. The etiology of familiar cases is unclear but appears genetically heterogeneous. This motivated us to report a case of OAVS with microtia, ptosis, facial microsomy, and fusion of vertebral bodies associated with a novel genetic etiology, including a deletion at 1p36.12-13. This case report expands on the genetic etiology of OAVS. Furthermore, it also expands the clinical manifestations of patients with interstitial deletions of the de 1p36.12-13 region.

UNASSIGNED: Approximately 1 in 1000 men have a 47,XYY karyotype. Previous publications have presented cases of infertile XYY men and have suggested that the additional Y chromosome may cause disrupted meiosis leading to sperm apoptosis. The purpose of the current study was to determine whether XYY men are over-represented in infertility cohorts.
UNASSIGNED: In this paper, an ongoing infertility cohort was evaluated for Y chromosome microdeletions using the MLPA technique and the data from the first 2000 referrals were recorded. Moreover, the MLPA technique detected 47,XYY karyotypes.
UNASSIGNED: Four XYY individuals were identified within the cohort. One of the four XYY men was shown to have an apparent gr/gr partial AZFc deletion on both Y chromosomes while Sertoli cell only syndrome was detected in another case. The other two cases (out of 2000) might, therefore, represent an incidental finding.
UNASSIGNED: The gr/gr deletion is not detectable by the multiplex PCR method; therefore, there might be additional explanations for the fertility problems of infertile XYY men reported in previously published articles. It seems that among other cases, their XYY karyotype may be coincidental, rather than causative of their fertility issues.

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype-phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.

Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) seriously affects rice yield production. The discovery and application of broad-spectrum resistance genes are of great advance for disease resistance breeding. Previously, we identified that multiple receptor-like kinase (RLK) family gene deletions induced by the Ac/Ds system resulted in a lesion mimic symptom. In this study, the mutant #29 showed that this lesion mimic symptom was isolated. Further analysis identified that four RLK genes (RLK19-22) were deleted in the #29 mutant. The #29 mutant exhibited broad-spectrum resistance to Xoo and subsequent analyses identified that pathogenesis-related genes PR1a, PBZ1, and cellular H2O2 levels were significantly induced in the mutant compared to wild-type plants. A genetic analysis revealed that reconstruction of RLK20, RLK21, or RLK22 rescued the lesion mimic symptom of the #29 mutant, indicating that these three RLKs are responsible for broad-spectrum resistance in rice. Further yeast two hybrid and bimolecular fluorescence complementation assays demonstrated that RLK20 interacts with RBOHB, which is a ROS producer in plants. Compared to wild-type plants, the #29 mutant was more, while #29/RLK20ox was less, susceptible to MV (methyl-viologen), an ROS inducer. Co-expression of RLK20 and RBOHB reduced RBOHB-promoted H2O2 accumulation in the cells. Taken together, our research indicated that the RLKs may inhibit RBOHB activity to negatively regulate rice resistance to Xoo. These results provide the theoretical basis and valuable information about the target genes necessary for the successful breeding of rice cultivars resistant to bacterial blight.

Chromosomal abnormality causes congenital and acquired intractable diseases. In general, there are no fundamental treatments for these diseases. To establish platforms to develop therapeutics for these diseases, patient-derived induced pluripotent stem cells (iPSCs) are highly beneficial. To study abnormal chromosomal diseases, it is often hard to apply animal disease models because the chromosomal structures are variable among species. It is also difficult to apply simple genome editing technology in cells or individuals for abnormal chromosomes. Thus, these patient-derived iPSCs have advantages for developing disease models with multiple cell and tissue types, which are typically seen in the symptoms of abnormal chromosomal diseases. Here we review the studies of patient-derived iPSCs carrying abnormal chromosomes, focusing on pluripotent state and neural lineages. We also discuss the technological advances in chromosomal manipulations toward establishing experimental models and future therapeutics. Patient-derived iPSCs carrying chromosomal abnormality are valuable as cellular bioresources since they can indefinitely proliferate and provide various cell types. Also, these findings and technologies are important for future studies on elucidating pathogenesis, drug development, regenerative medicine, and gene therapy for abnormal chromosomal diseases.

Genotype imputation, often focused on SNP and small insertions and deletions (indels; size ≤50 bp), is a crucial step for association mapping and estimation of genomic breeding values. Here, we present strategies to impute genotypes for large chromosomal deletions (size >50 bp), along with SNP and indels in cattle. The pipelines include a strategy for extending the whole-genome sequence reference panel for large deletions, a 2-step genotype refinement approach using Beagle4 and SHAPEIT2 software, and finally, joint imputation of SNP, indels, and large deletions to the existing SNP array-typed population using Minimac3 software. Using these pipelines we achieved an imputation accuracy of the squared Pearson correlation (r2) > 0.6 at minor allele frequencies as low as 0.7% for SNP and indels, and 0.2% for large deletions. This highlights the potential of our approach to build a haplotype reference panel and impute different classes of sequence variants across a wide allele frequency spectrum with high accuracy.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder resulting from chromosomal duplications, deletions, or imprinting within the 15q11-q13 region. In most cases, patients with PWS inherit a de novo paternally inherited deletion, and the remaining result from maternal disomy 15 and imprinting. Currently, DNA methylation analysis remains the gold standard for diagnosing PWS. However, this diagnostic test provides no information concerning the molecular class of PWS. As a result, clinicians remain unable to accurately determine diagnostic and prognostic information for patients with PWS. Further research is needed toward establishing standardized, accurate, and cost-effective testing methods for diagnosis and treatment of patients with PWS.