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Adaptation to changing environmental conditions represents a challenge to parthenogenetic organisms, and until now, how phenotypic variants are generated in clones in response to the selection pressure of their environment remains poorly known. The obligatory parthenogenetic root‐knot nematode species Meloidogyne incognita has a worldwide distribution and is the most devastating plant‐parasitic nematode. Despite its asexual reproduction, this species exhibits an unexpected capacity of adaptation to environmental constraints, for example, resistant hosts. Here, we used a genomewide comparative hybridization strategy to evaluate variations in gene copy numbers between genotypes of M. incognita resulting from two parallel experimental evolution assays on a susceptible vs. resistant host plant. We detected gene copy number variations (CNVs) associated with the ability of the nematodes to overcome resistance of the host plant, and this genetic variation may reflect an adaptive response to host resistance in this parthenogenetic species. The CNV distribution throughout the nematode genome is not random and suggests the occurrence of genomic regions more prone to undergo duplications and losses in response to the selection pressure of the host resistance. Furthermore, our analysis revealed an outstanding level of gene loss events in nematode genotypes that have overcome the resistance. Overall, our results support the view that gene loss could be a common class of adaptive genetic mechanism in response to a challenging new biotic environment in clonal animals. [ABSTRACT FROM AUTHOR]

Gene copy number variation ( CNV) has been associated with phenotypic variability in animals and plants, but a genomewide understanding of their impacts on phenotypes is largely restricted to human and agricultural systems. As such, CNVs have rarely been considered in investigations of the genomic architecture of adaptation in wild species. Here, we report on the genetic mapping of gene CNVs in white spruce, which lacks a contiguous assembly of its large genome (~20 Gb), and their relationships with adaptive phenotypic variation. We detected 3,911 gene CNVs including de novo structural variations using comparative genome hybridization on arrays ( aCGH) in a large progeny set. We inferred the heterozygosity at CNV loci within parents by comparing haploid and diploid tissues and genetically mapped 82 gene CNVs. Our analysis showed that CNVs were distributed over 10 linkage groups and identified four CNV hotspots that we predict to occur in other species of the Pinaceae. Significant relationships were found between 29 of the gene CNVs and adaptive traits based on regression analyses with timings of bud set and bud flush, and height growth, suggesting a role for CNVs in climate adaptation. The importance of CNVs in adaptive evolution of white spruce was also indicated by functional gene annotations and the clustering of 31% of the mapped adaptive gene CNVs in CNV hotspots. Taken together, these results illustrate the feasibility of studying CNVs in undomesticated species and represent a major step towards a better understanding of the roles of CNVs in adaptive evolution. [ABSTRACT FROM AUTHOR]

Genetic deficiencies of early components of the classical complement activation pathway (especially C1q, r, s, and C4) are the strongest monogenic causal factors for the prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency of C4A and acquired deficiency of C1q by autoantibodies are frequent among patients with SLE. Here we review the genetic basis of complement deficiencies in autoimmune disease, discuss the complex genetic diversity seen in complement C4 and its association with autoimmune disease, provide guidance as to when clinicians should suspect and test for complement deficiencies, and outline the current understanding of the mechanisms relating complement deficiencies to autoimmunity. We focus primarily on SLE, as the role of complement in SLE is well-established, but will also discuss other informative diseases such as inflammatory arthritis and myositis. • Complement plays a role in autoimmune disease as well as host defense. • We will discuss putative mechanisms by which complement contributes to autoimmunity. • The clinical history, physical exam, and laboratory findings seen in patients with complement deficiencies will be reviewed. • C1q and C4 are most strongly associated with autoimmune disease. • In addition to complement's role in SLE, this review will also address autoimmune myopathy, arthritis, and type I diabetes mellitus. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the mutation profiles of targeted genes and copy number variations (CNVs) in normal cytogenetics (CN) pediatric acute myeloid leukemia (AML). This prospective study was conducted from October 2018 to December 2020. The next-generation sequencing (NGS) and chromosomal microarray analyses (CMA) were performed in pediatric CN-AML patients. Out of 94 children (aged ≤18 years), 70 patients with AML (24 excluded) underwent conventional karyotyping/cytogenetic analyses. Forty-five (64.3%) of patients had abnormal/ recurrent cytogenetic abnormalities and 25 (35.7%) had normal cytogenetics. Twenty-three out of 25 CN-AML were further processed for gene mutation profile and CNVs using NGS and CMA, respectively. Twenty-two out of 23 (95.7%) patients were detected to have mutations in various genes. The common mutations were: NRAS, NPM1, CEBPA, KRAS, KIT, RUNX1, NOTCH1, WT1, GATA1, GATA2, FLT3, KMT2D, FLT3-TKD, and PHF6. Copy number variations (CNVs) were detected in nine patients (39%), and eight (34.8%) had a long contiguous stretch of homozygosity (LCSH) /loss of heterozygosity (LOH). An LCSH was detected on chromosomes 5, 7, 11, and 19. The gains were more common than losses (8 vs 2). The gains were observed on chromosomes 8, 9, 14, 19, 21, and 22, and the losses were detected on chromosomes 7 and 10. Monosomy was observed in three patients. Three patients (monosomy7, n = 2, and FLT-ITD, n = 1) were reclassified into the high-risk category. Post-induction, complete remission was achieved in all evaluable patients. CN-AML patients have genetic abnormalities that can be detected by more advanced techniques like NGS and CMA. These genetic abnormalities play a role in risk stratification that may remain hidden in otherwise CN-AML. • Normal cytogenetics (CN) AML is currently categorized as intermediate risk, yet this group is quite heterogeneous. In this study, 64.3% of patients had recurrent cytogenetic abnormalities, and 35.7% had normal cytogenetics. • Twenty-two out of 23 (95.7%) patients with CN-AML were detected to have mutations in various genes. The common mutations were: NRAS, NPM1, CEBPA, KRAS, KIT, RUNX1, NOTCH1, WT1, GATA1, GATA2, FLT3, KMT2D, FLT3-TKD, and PHF6. • Copy number variations (CNVs) were detected in nine patients (39%), and eight (34.8%) had a long contiguous stretch of homozygosity (LCSH) /loss of heterozygosity (LOH). An LCSH was detected on chromosomes 5, 7, 11, and 19. The gains were more common than losses (8 vs 2). Monosomy was observed in three patients. • Three patients (monosomy 7, n = 2 and FLT-ITD, n = 1)] were reclassified into the high-risk category. [ABSTRACT FROM AUTHOR]

Background: Understanding the genetic basis of adaptive evolution is one of the major goals in evolutionary biology. Recently, it has been revealed that gene copy number variations (GCNVs) constitute significant proportions of genomic diversities within natural populations. However, it has been unclear whether GCNVs are under positive selection and contribute to adaptive evolution. Parallel evolution refers to adaptive evolution of the same trait in related but independent lineages, and three-spined stickleback (Gasterosteus aculeatus) is a well-known model organism. Through identification of genetic variations under parallel selection, i.e., variations shared among related but independent lineages, evidence of positive selection is obtained. In this study, we investigated whole-genome resequencing data from the marine and freshwater groups of three-spined sticklebacks from diverse areas along the Pacific and Atlantic Ocean coastlines, and searched for GCNVs under parallel selection. Results: We identified 24 GCNVs that showed significant differences in the numbers of mapped reads between the two groups, and this number was significantly larger than that expected by chance. The derived group, i.e., freshwater group, was typically characterized by larger gene-copy numbers, which implied that gene duplications or multiplications helped with adaptation to the freshwater environment. Some of the identified GCNVs were those of multigenic family genes, which is consistent with the theory that fatal effects due to copy-number changes of multigenic family genes tend to be less than those of single-copy genes. Conclusion: The identification of GCNVs that were likely under parallel selection suggests that contribution of GCNVs should be considered in studies on adaptive evolution. [ABSTRACT FROM AUTHOR]

Background: Detection of ALK and ROS1 gene rearrangements in non-small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation., Patients and Methods: Forty non-small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated., Results: NGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026)., Conclusion: Our data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Our recent study demonstrated that cancer cells with compromised glutathione homeostasis, including reduced expression of the glutathione reductase ( GSR ) gene, were selectively killed by inhibition of thioredoxin reductase. The human GSR gene is located on chromosome 8p, a region often lost in lung and other cancers. However, whether GSR is altered in primary lung cancer remains unknown. To analyze alterations of GSR in lung cancer, we performed fluorescence in situ hybridization with probes for GSR and the chromosome 8 centromere (CEP8) in 45 surgical specimens of primary lung cancer, including 24 lung adenocarcinomas, 10 squamous cell carcinomas, 8 neuroendocrine cancers, and 3 small cell lung cancers. Twenty-five surgically resected normal lung tissue specimens from these lung cancer patients were used as a controls. The signal ratio of GSR to CEP8 per cell was used to identify gain or loss of GSR . GSR loss was detected in 6 of 24 (25%) adenocarcinoma specimens and 5 of 10 (50%) squamous cell carcinoma specimens, but not in neuroendocrine cancer or small cell lung cancer specimens. We also found that 19 of 45 (42%) specimens had chromosome 8 aneuploidy (more or less than 2 signals for CEP8), including 8 with both aneuploidy and GSR deletion. Chromosome 8 aneuploidy was detected in all types of lung cancer analyzed. Univariate and multivariable logistic regression analyses indicated that male patients had an increased risk of GSR deletion (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 1.00-22.86, P = 0.051), and patients who had undergone preoperative radiation therapy or had a self-reported history of cigarette smoking had an increased risk of chromosome 8 aneuploidy (preoperative radiation: HR = 18.63, 95% CI = 0.90-384.17, P = 0.058; smoking: HR = 7.59, 95% CI = 0.86-66.75, P = 0.068), although the p values did not reach significance. Because GSR deficiency and chromosome 8 aneuploidy have implications in targeted therapy and/or immunotherapy for cancer, they might serve as predictive biomarkers for precision therapy of lung cancers., Competing Interests: None.

Objectives: To explore the chromosomal analysis for fetuses with nasal bone absence or hypoplasia. Methods: This was a retrospective study on 29 pregnancies nasal bone absence or hypoplasia which underwent prenatal diagnosis, including chorionic villi (CV), amniotic fluid or cordocentesis.The indication of the procedures and results were evaluated. Result: Fifteen (51.7%, 15/29) of chromosome abnormities were diagnosed with indication of fetal nasal bone absence or hypoplasia, including eight with trisomy 21, two with trisomy 13, two with X chromosome aneuploidy and three with pathogenic copy number variations (CNVs) respectively.The incidence of chromosomal abnormalities in fetus with nasal bone hypoplasia (2/5, 40%) was lower than that in fetus with nasal bone absence (13/29, 54.2%). The incidence of chromosomal abnormalities in fetus with non-syndromic nasal bone absence or hypoplasia (4/13) was lower than that in fetus with syndromic nasal bone absence or hypoplasia (11/16). Conclusion: The incidence of chromosomal abnormalities in fetus with nasal bone absence or hypoplasia was higher and prenatal diagnosis was recommended for all types of the disease.For the fetus with nasal bone absence or hypoplasia, it is recommended to give priority to CNVs for prenatal diagnosis.