Taxonomic status of the Liberian Greenbul Phyllastrephus leucolepis and the conservation importance of the Cavalla Forest, Liberia

We thank Jochen Martens for his long-lasting patience in dealing with the specimen of leucolepis, and Brian Hillcoat for comments and advice. It is hardly possible to thank by name all those who have supported WG over the past 30 years and more since 1981 in the fields of forest ecology and ornithology in eastern Liberia. In particular, we express gratitude to Alex Peal and Theo Freeman, both Heads of Wildlife and National Parks, for their many years of cooperation, and the Silviculture Officers Wynn Bryant, Momo Kromah and Steve Miapeh. The knowledge of the tree experts Joe Keper and Daniel Dorbor helped us to gain insights into the ecological complexities of the relationship between man, birds and trees. William Toe worked for three years as bird trapper and assistant in bird banding. WG’s attachment to the University of Liberia and to the students who so often accompanied him was made possible by Ben Karmorh from the Environmental Protection Agency (EPA) and University of Liberia. NABU, the German Conservation Society, has supported the Liberian projects for almost 30 years now. We also thank Nigel Collar, Françoise Dowsett-Lemaire and Hannah Rowland for comments and advice. We thank the African Bird Club and the Royal Society for the Protection of Birds for helping to fund the 2013 expedition to the Cavalla Forest, in particular Alice Ward-Francis, Robert Sheldon, Alan Williams and Keith Betton. We also are extremely grateful to Michael Garbo and staff of the Society for the Conservation of Nature in Liberia for all manner of help with the expedition, to Harrison Karnwea and colleagues at the Forest Development Authority of Liberia for permissions and other support, as well as to Emmanuel Loqueh, Trokon Grimes, Flomo Molubah and Amos ‘Dweh’ Dorbor for being such excellent companions in the field. YL performed the genetic work as part of her M.Sc. (Genetics) at the University of Aberdeen, whose support is acknowledged.Peer reviewedPublisher PD

SYSTEMATIC PLACEMENT OF THE BEE HUMMINGBIRD (MELLISUGA HELENAE) (AVES: TROCHILIDAE) AND POTENTIAL CONSEQUENCES FOR NOMENCLATURE OF THE MELLISUGINAE

The Near Threatened Cuban endemic, Bee Hummingbird Mellisuga helenae, is iconic for its tiny size—the male is the smallest bird in the world. In this study, one mitochondrial gene (ND2) and introns of two nuclear genes (encoding adenylate kinase and beta-fibrinogen), were sequenced and aligned to homologous sequences from other hummingbird species. With high statistical support, both Maximum Likelihood and Bayesian analyses resolved Bee Hummingbird as sister to Bahama and Inagua Hummingbirds Calliphlox (or Nesophlox) evelynae and lyrura, rather than the congeneric Vervain Hummingbird Mellisuga minima. This finding highlights the need for nomenclatural rearrangement of several hummingbird species in line with the results of recent molecular phylogenies

First genetic data for the critically endangered Cuban endemic Zapata Rail Cyanolimnas cerverai, and the taxonomic implications

Funding Information: GMK and AK are grateful to staff, particularly Ianela García-Lau, Manolo Barro and volunteers at the Museo de Historia Natural ‘Felipe Poey’, La Habana, Cuba, for access to relevant specimens. This study was funded by University of Aberdeen (AB) and The Sound Approach Ph.D. Studentship (TJS).Peer reviewedPublisher PD

The taxonomic position and breeding range of Golden Nightjar Caprimulgus eximius (Caprimulgidae)

Acknowledgements YL performed this research as part of her MSc (Genetics) at the University of Aberdeen, whose support is acknowledged. We thank the reviewers whose helpful comments substantially improved the paper.Peer reviewedPostprin

When morphology is not reflected by molecular phylogeny : the case of three ‘orange-billed terns’ Thalasseus maximus, T. bergii and T. bengalensis (Charadriiformes: Laridae).

In The Gambia we would like to thank The Director of Department Park and Wildlife Management, Mr Lamin Gassama, for access to the Bijol Islands. We thank staff of Tanji Bird Reserve and Mr Mawdo Jallow, Research and Development, who facilitated the export document for research materials. We thank Jan Veen for information on Senegalese colonies. We thank the reviewers whose helpful comments lead to very significant improvements in the paper.Peer reviewedPostprin

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of &lt;1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation. </jats:sec

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre