Does it pay to pay? A comparison of the benefits of open-access publishing across various sub-fields in biology.

Authors are often faced with the decision of whether to maximize traditional impact metrics or minimize costs when choosing where to publish the results of their research. Many subscription-based journals now offer the option of paying an article processing charge (APC) to make their work open. Though such "hybrid" journals make research more accessible to readers, their APCs often come with high price tags and can exclude authors who lack the capacity to pay to make their research accessible. Here, we tested if paying to publish open access in a subscription-based journal benefited authors by conferring more citations relative to closed access articles. We identified 146,415 articles published in 152 hybrid journals in the field of biology from 2013-2018 to compare the number of citations between various types of open access and closed access articles. In a simple generalized linear model analysis of our full dataset, we found that publishing open access in hybrid journals that offer the option confers an average citation advantage to authors of 17.8 citations compared to closed access articles in similar journals. After taking into account the number of authors, Journal Citation Reports 2020 Quartile, year of publication, and Web of Science category, we still found that open access generated significantly more citations than closed access (p < 0.0001). However, results were complex, with exact differences in citation rates among access types impacted by these other variables. This citation advantage based on access type was even similar when comparing open and closed access articles published in the same issue of a journal (p < 0.0001). However, by examining articles where the authors paid an article processing charge, we found that cost itself was not predictive of citation rates (p = 0.14). Based on our findings of access type and other model parameters, we suggest that, in the case of the 152 journals we analyzed, paying for open access does confer a citation advantage. For authors with limited budgets, we recommend pursuing open access alternatives that do not require paying a fee as they still yielded more citations than closed access. For authors who are considering where to submit their next article, we offer additional suggestions on how to balance exposure via citations with publishing costs.

What makes a winner? Symbiont and host dynamics determine Caribbean octocoral resilience to bleaching.

Unlike reef-building, scleractinian corals, Caribbean soft corals (octocorals) have not suffered marked declines in abundance associated with anthropogenic ocean warming. Both octocorals and reef-building scleractinians depend on a nutritional symbiosis with single-celled algae living within their tissues. In both groups, increased ocean temperatures can induce symbiont loss (bleaching) and coral death. Multiple heat waves from 2014 to 2016 resulted in widespread damage to reef ecosystems and provided an opportunity to examine the bleaching response of three Caribbean octocoral species. Symbiont densities declined during the heat waves but recovered quickly, and colony mortality was low. The dominant symbiont genotypes within a host generally did not change, and all colonies hosted symbiont species in the genus Breviolum. Their association with thermally tolerant symbionts likely contributes to the octocoral holobiont's resistance to mortality and the resilience of their symbiont populations. The resistance and resilience of Caribbean octocorals offer clues for the future of coral reefs.

A 14th century CE Brucella melitensis genome and the recent expansion of the Western Mediterranean clade.

Brucellosis is a disease caused by the bacterium Brucella and typically transmitted through contact with infected ruminants. It is one of the most common chronic zoonotic diseases and of particular interest to public health agencies. Despite its well-known transmission history and characteristic symptoms, we lack a more complete understanding of the evolutionary history of its best-known species-Brucella melitensis. To address this knowledge gap we fortuitously found, sequenced and assembled a high-quality ancient B. melitensis draft genome from the kidney stone of a 14th-century Italian friar. The ancient strain contained fewer core genes than modern B. melitensis isolates, carried a complete complement of virulence genes, and did not contain any indication of significant antimicrobial resistances. The ancient B. melitensis genome fell as a basal sister lineage to a subgroup of B. melitensis strains within the Western Mediterranean phylogenetic group, with a short branch length indicative of its earlier sampling time, along with a similar gene content. By calibrating the molecular clock we suggest that the speciation event between B. melitensis and B. abortus is contemporaneous with the estimated time frame for the domestication of both sheep and goats. These results confirm the existence of the Western Mediterranean clade as a separate group in the 14th CE and suggest that its divergence was due to human and ruminant co-migration.

Reply to Barton et al: signatures of natural selection during the Black Death.

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2×10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

A meta-analysis of the stony coral tissue loss disease microbiome finds key bacteria in unaffected and lesion tissue in diseased colonies.

Stony coral tissue loss disease (SCTLD) has been causing significant whole colony mortality on reefs in Florida and the Caribbean. The cause of SCTLD remains unknown, with the limited concurrence of SCTLD-associated bacteria among studies. We conducted a meta-analysis of 16S ribosomal RNA gene datasets generated by 16 field and laboratory SCTLD studies to find consistent bacteria associated with SCTLD across disease zones (vulnerable, endemic, and epidemic), coral species, coral compartments (mucus, tissue, and skeleton), and colony health states (apparently healthy colony tissue (AH), and unaffected (DU) and lesion (DL) tissue from diseased colonies). We also evaluated bacteria in seawater and sediment, which may be sources of SCTLD transmission. Although AH colonies in endemic and epidemic zones harbor bacteria associated with SCTLD lesions, and aquaria and field samples had distinct microbial compositions, there were still clear differences in the microbial composition among AH, DU, and DL in the combined dataset. Alpha-diversity between AH and DL was not different; however, DU showed increased alpha-diversity compared to AH, indicating that, prior to lesion formation, corals may undergo a disturbance to the microbiome. This disturbance may be driven by Flavobacteriales, which were especially enriched in DU. In DL, Rhodobacterales and Peptostreptococcales-Tissierellales were prominent in structuring microbial interactions. We also predict an enrichment of an alpha-toxin in DL samples which is typically found in Clostridia. We provide a consensus of SCTLD-associated bacteria prior to and during lesion formation and identify how these taxa vary across studies, coral species, coral compartments, seawater, and sediment.

Emergence, continuity, and evolution of Yersinia pestis throughout medieval and early modern Denmark.

The historical epidemiology of plague is controversial due to the scarcity and ambiguity of available data.1,2 A common source of debate is the extent and pattern of plague re-emergence and local continuity in Europe during the 14th-18th century CE.3 Despite having a uniquely long history of plague (∼5,000 years), Scandinavia is relatively underrepresented in the historical archives.4,5 To better understand the historical epidemiology and evolutionary history of plague in this region, we performed in-depth (n = 298) longitudinal screening (800 years) for the plague bacterium Yersinia pestis (Y. pestis) across 13 archaeological sites in Denmark from 1000 to 1800 CE. Our genomic and phylogenetic data captured the emergence, continuity, and evolution of Y. pestis in this region over a period of 300 years (14th-17th century CE), for which the plague-positivity rate was 8.3% (3.3%-14.3% by site). Our phylogenetic analysis revealed that the Danish Y. pestis sequences were interspersed with those from other European countries, rather than forming a single cluster, indicative of the generation, spread, and replacement of bacterial variants through communities rather than their long-term local persistence. These results provide an epidemiological link between Y. pestis and the unknown pestilence that afflicted medieval and early modern Europe. They also demonstrate how population-scale genomic evidence can be used to test hypotheses on disease mortality and epidemiology and help pave the way for the next generation of historical disease research.

Plagued by a cryptic clock: insight and issues from the global phylogeny of Yersinia pestis.

Plague has an enigmatic history as a zoonotic pathogen. This infectious disease will unexpectedly appear in human populations and disappear just as suddenly. As a result, a long-standing line of inquiry has been to estimate when and where plague appeared in the past. However, there have been significant disparities between phylogenetic studies of the causative bacterium, Yersinia pestis, regarding the timing and geographic origins of its reemergence. Here, we curate and contextualize an updated phylogeny of Y. pestis using 601 genome sequences sampled globally. Through a detailed Bayesian evaluation of temporal signal in subsets of these data we demonstrate that a Y. pestis-wide molecular clock is unstable. To resolve this, we developed a new approach in which each Y. pestis population was assessed independently, enabling us to recover substantial temporal signal in five populations, including the ancient pandemic lineages which we now estimate may have emerged decades, or even centuries, before a pandemic was historically documented from European sources. Despite this methodological advancement, we only obtain robust divergence dates from populations sampled over a period of at least 90 years, indicating that genetic evidence alone is insufficient for accurately reconstructing the timing and spread of short-term plague epidemics.

A highly effective therapeutic ointment for treating corals with black band disease.

Infectious disease outbreaks are a primary contributor to coral reef decline worldwide. A particularly lethal disease, black band disease (BBD), was one of the first coral diseases reported and has since been documented on reefs worldwide. BBD is described as a microbial consortium of photosynthetic cyanobacteria, sulfate-reducing and sulfide-oxidizing bacteria, and heterotrophic bacteria and archaea. The disease is visually identified by a characteristic dark band that moves across apparently healthy coral tissue leaving behind bare skeleton. Despite its virulence, attempts to effectively treat corals with BBD in the field have been limited. Here, we developed and tested several different therapeutic agents on Pseudodiploria spp. corals with signs of active BBD at Buck Island Reef National Monument in St. Croix, USVI. A variety of therapies were tested, including hydrogen peroxide-based treatments, ointment containing antibiotics, and antiviral/antimicrobial-based ointments (referred to as CoralCure). The CoralCure ointments, created by Ocean Alchemists LLC, focused on the dosing regimen and delivery mechanisms of the different active ingredients. Active ingredients included carbamide peroxide, Lugol's iodine solution, along with several proprietary essential oil and natural product blends. Additionally, the active ingredients had different release times based on treatment: CoralCure A-C had a release time of 24 hours, CoralCure D-F had a release time of 72 hours. The ointments were applied directly to the BBD lesion. Also, jute rope was saturated with a subset of these CoralCure ointment formulations to assist with adhesion. These ropes were then applied to the leading edge of the BBD lesion for one week to ensure sufficient exposure. Corals were revisited approximately three to five months after treatment application to assess disease progression rates and the presence/absence of lesions-the metrics used to quantify the efficacy of each treatment. Although most of the treatments were unsuccessful, two CoralCure rope formulations-CoralCure D rope and CoralCure E rope, eliminated the appearance of BBD in 100% of the corals treated. As such, these treatments significantly reduced the likelihood of BBD occurrence compared to the untreated controls. Additionally, lesions treated with these formulations lost significantly less tissue compared with controls. These results provide the mechanisms for an easily employable method to effectively treat a worldwide coral disease.

Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Examining pathogen DNA recovery across the remains of a 14th century Italian friar (Blessed Sante) infected with Brucella melitensis.

OBJECTIVE: To investigate variation in ancient DNA recovery of Brucella melitensis, the causative agent of brucellosis, from multiple tissues belonging to one individual MATERIALS: 14 samples were analyzed from the mummified remains of the Blessed Sante, a 14 th century Franciscan friar from central Italy, with macroscopic diagnosis of probable brucellosis. METHODS: Shotgun sequencing data from was examined to determine the presence of Brucella DNA. RESULTS: Three of the 14 samples contained authentic ancient DNA, identified as belonging to B. melitensis. A genome (23.81X depth coverage, 0.98 breadth coverage) was recovered from a kidney stone. Nine of the samples contained reads classified as B. melitensis (7-169), but for many the data quality was insufficient to withstand our identification and authentication criteria. CONCLUSIONS: We identified significant variation in the preservation and abundance of B. melitensis DNA present across multiple tissues, with calcified nodules yielding the highest number of authenticated reads. This shows how greatly sample selection can impact pathogen identification. SIGNIFICANCE: Our results demonstrate variation in the preservation and recovery of pathogen DNA across tissues. This study highlights the importance of sample selection in the reconstruction of infectious disease burden and highlights the importance of a holistic approach to identifying disease. LIMITATIONS: Study focuses on pathogen recovery in a single individual. SUGGESTIONS FOR FURTHER RESEARCH: Further analysis of how sampling impacts aDNA recovery will improve pathogen aDNA recovery and advance our understanding of disease in past peoples.

Pleistocene mitogenomes reconstructed from the environmental DNA of permafrost sediments.

Traditionally, paleontologists have relied on the morphological features of bones and teeth to reconstruct the evolutionary relationships of extinct animals.1 In recent decades, the analysis of ancient DNA recovered from macrofossils has provided a powerful means to evaluate these hypotheses and develop novel phylogenetic models.2 Although a great deal of life history data can be extracted from bones, their scarcity and associated biases limit their information potential. The paleontological record of Beringia3-the unglaciated areas and former land bridge between northeast Eurasia and northwest North America-is relatively robust thanks to its perennially frozen ground favoring fossil preservation.4,5 However, even here, the macrofossil record is significantly lacking in small-bodied fauna (e.g., rodents and birds), whereas questions related to migration and extirpation, even among well-studied taxa, remain crudely resolved. The growing sophistication of ancient environmental DNA (eDNA) methods have allowed for the identification of species within terrestrial/aquatic ecosystems,6-12 in paleodietary reconstructions,13-19 and facilitated genomic reconstructions from cave contexts.8,20-22 Murchie et al.6,23 used a capture enrichment approach to sequence a diverse range of faunal and floral DNA from permafrost silts deposited during the Pleistocene-Holocene transition.24 Here, we expand on their work with the mitogenomic assembly and phylogenetic placement of Equus caballus (caballine horse), Bison priscus (steppe bison), Mammuthus primigenius (woolly mammoth), and Lagopus lagopus (willow ptarmigan) eDNA from multiple permafrost cores spanning the last 40,000 years. We identify a diverse metagenomic spectra of Pleistocene fauna and identify the eDNA co-occurrence of distinct Eurasian and American mitogenomic lineages.

Heritable variation and lack of tradeoffs suggest adaptive capacity in Acropora cervicornis despite negative synergism under climate change scenarios.

Knowledge of multi-stressor interactions and the potential for tradeoffs among tolerance traits is essential for developing intervention strategies for the conservation and restoration of reef ecosystems in a changing climate. Thermal extremes and acidification are two major co-occurring stresses predicted to limit the recovery of vital Caribbean reef-building corals. Here, we conducted an aquarium-based experiment to quantify the effects of increased water temperatures and pCO2 individually and in concert on 12 genotypes of the endangered branching coral Acropora cervicornis, currently being reared and outplanted for large-scale coral restoration. Quantification of 12 host, symbiont and holobiont traits throughout the two-month-long experiment showed several synergistic negative effects, where the combined stress treatment often caused a greater reduction in physiological function than the individual stressors alone. However, we found significant genetic variation for most traits and positive trait correlations among treatments indicating an apparent lack of tradeoffs, suggesting that adaptive evolution will not be constrained. Our results suggest that it may be possible to incorporate climate-resistant coral genotypes into restoration and selective breeding programmes, potentially accelerating adaptation.

Nanopore Amplicon Sequencing Reveals Molecular Convergence and Local Adaptation of Rhodopsin in Great Lakes Salmonids.

Local adaptation can drive diversification of closely related species across environmental gradients and promote convergence of distantly related taxa that experience similar conditions. We examined a potential case of adaptation to novel visual environments in a species flock (Great Lakes salmonids, genus Coregonus) using a new amplicon genotyping protocol on the Oxford Nanopore Flongle and MinION. We sequenced five visual opsin genes for individuals of Coregonus artedi, Coregonus hoyi, Coregonus kiyi, and Coregonus zenithicus. Comparisons revealed species-specific differences in a key spectral tuning amino acid in rhodopsin (Tyr261Phe substitution), suggesting local adaptation of C. kiyi to the blue-shifted depths of Lake Superior. Ancestral state reconstruction demonstrates that parallel evolution and "toggling" at this amino acid residue has occurred several times across the fish tree of life, resulting in identical changes to the visual systems of distantly related taxa across replicated environmental gradients. Our results suggest that ecological differences and local adaptation to distinct visual environments are strong drivers of both evolutionary parallelism and diversification.

Genetic resiliency and the Black Death: No apparent loss of mitogenomic diversity due to the Black Death in medieval London and Denmark.

OBJECTIVES: In the 14th century AD, medieval Europe was severely affected by the Great European Famine as well as repeated bouts of disease, including the Black Death, causing major demographic shifts. This high volatility led to increased mobility and migration due to new labor and economic opportunities, as evidenced by documentary and stable isotope data. This study uses ancient DNA (aDNA) isolated from skeletal remains to examine whether evidence for large-scale population movement can be gleaned from the complete mitochondrial genomes of 264 medieval individuals from England (London) and Denmark. MATERIALS AND METHODS: Using a novel library-conserving approach to targeted capture, we recovered 264 full mitochondrial genomes from the petrous portion of the temporal bones and teeth and compared genetic diversity across the medieval period within and between English (London) and Danish populations and with contemporary populations through population pairwise ΦST analysis. RESULTS: We find no evidence of significant differences in genetic diversity spatially or temporally in our dataset, yet there is a high degree of haplotype diversity in our medieval samples with little exact sequence sharing. DISCUSSION: The mitochondrial genomes of both medieval Londoners and medieval Danes suggest high mitochondrial diversity before, during and after the Black Death. While our mitochondrial genomic data lack geographically correlated signals, these data could be the result of high, continual female migration before and after the Black Death or may simply indicate a large female effective population size unaffected by the upheaval of the medieval period. Either scenario suggests a genetic resiliency in areas of northwestern medieval Europe.

On the fundamental comparison between unfocused and focused light field cameras.

Light field cameras have been extensively used in a variety of applications, thanks to their snapshot three-dimensional imaging capability. However, little is known regarding their pros and cons for a given application. Herein we report a fundamental comparison between two types of light field cameras-focused and unfocused. Our results indicate that the unfocused light field camera outperforms its focused counterpart in depth range and number of resolvable depth steps, while the focused light field camera has an edge in lateral resolution and reconstruction accuracy.

Association study confirms the role of two OCA2 polymorphisms in normal skin pigmentation variation in East Asian populations.

OBJECTIVES: The main goal of the study was to test the association of 18 polymorphisms located within nine pigmentation candidate genes with quantitative skin pigmentation measures collected in a sample of individuals of East Asian ancestry living in Canada (N = 419). METHODS: The 18 polymorphisms are located within genes that show putative signatures of positive selection in East Asian populations. The genetic markers were selected for genotyping based on an annotation of common East Asian polymorphisms to predict potential functional effects. We restricted our attention to polymorphisms that have an allele frequency difference of at least 30% between East Asian populations and African and European populations, or have alleles that are present in East Asians, but are absent in Africans and Europeans. RESULTS: Two nonsynonymous variants selected within the OCA2 gene, rs1800414 (His615Arg) and rs74653330 (Ala481Thr), were significantly associated with melanin levels in the sample. Both single nucleotide polymorphisms (SNPs) are nonsynonymous polymorphisms located more than 30 kb apart on chromosome 15 and have very different frequencies in the East Asian sample. Additionally, both polymorphisms are predicted to have a deleterious effect on the protein. Linear regression analysis using an additive model indicate that each copy of the derived rs1800414 allele G decreases Melanin Index approximately 0.9 units and each copy of the derived rs74653330 allele A decreases Melanin Index approximately 1.9 units. CONCLUSIONS: Two nonsynonymous OCA2 polymorphisms (rs1800414 and rs74653330) are independently associated with normal skin pigmentation variation in East Asian populations and have very different frequency distributions in East Asia.

Molecularly confirmed primary malignant rhabdoid tumor of the urinary bladder: implications of accurate diagnosis.

Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient's peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation.

Epithelioid malignant peripheral nerve sheath tumors arising in preexisting schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but 1 of which showed "neuroblastoma-like" histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and in 3 of her children, 2 of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain.

p16INK4A and p14ARF tumor suppressor pathways are deregulated in malignant rhabdoid tumors.

Malignant rhabdoid tumors (MRTs) are aggressive tumors associated with mutations in the SMARCB1 gene. In experimental systems, the loss of SMARCB1 is hypothesized to alter p16(INK4A) pathways resulting in the repression of tumor suppressors. To determine whether these pathways are deregulated in human MRT, we used immunohistochemistry on tissue microarrays to evaluate p16(INK4A)/E2F1/RB and p14(ARF)/MDM2/p53 pathways in 25 atypical teratoid/rhabdoid tumors (AT/RT) and 11 non-CNS MRT. p16(INK4A) was negative or showed focal weak expression. p16(INK4A) downstream targets CDK4/cyclin D1/ppRB were variably expressed at moderate to low levels; E2F1 was negative. Unexpectedly, p14(ARF) expression was seen in many cases, which correlated positively with p53 and inversely with MDM2 immunostaining in AT/RT. TP53 mutational analysis in 19 of 25 AT/RT and in 8 of 11 non-CNS MRT cases showed point mutations in only 3 AT/RT cases, suggesting that p53 expression was driven mainly by p14(ARF). Finally, nucleophosmin, a protein that stabilizes p53, was positive in most cases and colocalized with p53. Together, these data suggest that, in MRT, there is deregulation not only of p16(INK4A) but also of the p14(ARF) pathway. These results provide insights into cell cycle deregulation in the pathogenesis of human MRT and may aid in the design and evaluation of potential therapies for these tumors.

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.