| 1. |
- Heckman, Michael G., et al.
(författare)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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| 2. |
- Ross, Owen A., et al.
(författare)
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Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
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Tidskriftsartikel (refereegranskat)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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| 3. |
- Bacon, Christine D., et al.
(författare)
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Biogeography of the Malagasy Celastraceae: Multiple independent origins followed by widespread dispersal of genera from Madagascar
- 2016
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 94, s. 365-382
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Elsevier Inc.. Of the 97 currently recognized genera of Celastraceae, 19 are native to Madagascar, including six endemics. In this study we conducted the most thorough phylogenetic analysis of Celastraceae yet completed with respect to both character and taxon sampling, and include representatives of five new endemic genera. Fifty-one new accessions, together with 328 previously used accessions of Celastrales, were sampled for morphological characters, two rDNA gene regions, and two plastid gene regions. The endemic Malagasy genera are resolved in two separate lineages- Xenodrys by itself and all other endemic genera in a clade that also includes four lineages inferred to have dispersed from Madagascar: Brexia madagascariensis (Mascarene Islands, coastal Africa), Elaeodendron (West Indies, Africa to New Caledonia), and Pleurostylia (Africa to New Caledonia). Of the 12 extant Malagasy Celastraceae lineages identified, eight are clearly of African origin. The origins of the remaining four lineages are less clear, but reasonable possibilities include America, Eurasia, Africa, southern India, Malesia, and Australia. Based on 95% credible age intervals from fossil-calibrated molecular dating, all 12 extant Malagasy Celastraceae lineages appear to have arisen following dispersal after the separation of Madagascar from other landmasses within the last 70. million years.
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| 4. |
- Andermann, Tobias, et al.
(författare)
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A Guide to Carrying Out a Phylogenomic Target Sequence Capture Project
- 2020
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput DNA sequencing techniques enable time- and cost-effective sequencing of large portions of the genome. Instead of sequencing and annotating whole genomes, many phylogenetic studies focus sequencing effort on large sets of pre-selected loci, which further reduces costs and bioinformatic challenges while increasing coverage. One common approach that enriches loci before sequencing is often referred to as target sequence capture. This technique has been shown to be applicable to phylogenetic studies of greatly varying evolutionary depth. Moreover, it has proven to produce powerful, large multi-locus DNA sequence datasets suitable for phylogenetic analyses. However, target capture requires careful considerations, which may greatly affect the success of experiments. Here we provide a simple flowchart for designing phylogenomic target capture experiments. We discuss necessary decisions from the identification of target loci to the final bioinformatic processing of sequence data. We outline challenges and solutions related to the taxonomic scope, sample quality, and available genomic resources of target capture projects. We hope this review will serve as a useful roadmap for designing and carrying out successful phylogenetic target capture studies.
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| 5. |
- Andermann, Tobias, et al.
(författare)
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SECAPR-a bioinformatics pipeline for the rapid and user-friendly processing of targeted enriched Illumina sequences, from raw reads to alignments
- 2018
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Ingår i: Peerj. - : PeerJ. - 2167-8359. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary biology has entered an era of unprecedented amounts of DNA sequence data, as new sequencing technologies such as Massive Parallel Sequencing (MPS) can generate billions of nucleotides within less than a day. The current bottleneck is how to efficiently handle, process, and analyze such large amounts of data in an automated and reproducible way. To tackle these challenges we introduce the Sequence Capture Processor (SECAPR) pipeline for processing raw sequencing data into multiple sequence alignments for downstream phylogenetic and phylogeographic analyses. SECAPR is user-friendly and we provide an exhaustive empirical data tutorial intended for users with no prior experience with analyzing MPS output. SECAPR is particularly useful for the processing of sequence capture (synonyms: target or hybrid enrichment) datasets for non-model organisms, as we demonstrate using an empirical sequence capture dataset of the palm genus Geonoma (Arecaceae). Various quality control and plotting functions help the user to decide on the most suitable settings for even challenging datasets. SECAPR is an easy-to-use, free, and versatile pipeline, aimed to enable efficient and reproducible processing of MPS data for many samples in parallel.
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| 6. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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Amazonia is the primary source of Neotropical biodiversity
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:23, s. 6034-6039
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Tidskriftsartikel (refereegranskat)abstract
- The American tropics (the Neotropics) are the most species-rich realm on Earth, and for centuries, scientists have attempted to understand the origins and evolution of their biodiversity. It is now clear that different regions and taxonomic groups have responded differently to geological and climatic changes. However, we still lack a basic understanding of how Neotropical biodiversity was assembled over evolutionary timescales. Here we infer the timing and origin of the living biota in all major Neotropical regions by performing a cross-taxonomic biogeographic analysis based on 4,450 species from six major clades across the tree of life (angiosperms, birds, ferns, frogs, mammals, and squamates), and integrate > 1.3 million species occurrences with large-scale phylogenies. We report an unprecedented level of biotic interchange among all Neotropical regions, totaling 4,525 dispersal events. About half of these events involved transitions between major environmental types, with a predominant directionality from forested to open biomes. For all taxonomic groups surveyed here, Amazonia is the primary source of Neotropical diversity, providing > 2,800 lineages to other regions. Most of these dispersal events were to Mesoamerica (similar to 1,500 lineages), followed by dispersals into open regions of northern South America and the Cerrado and Chaco biomes. Biotic interchange has taken place for > 60 million years and generally increased toward the present. The total amount of time lineages spend in a region appears to be the strongest predictor of migration events. These results demonstrate the complex origin of tropical ecosystems and the key role of biotic interchange for the assembly of regional biotas.
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| 7. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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An engine for global plant diversity: Highest evolutionary turnover and emigration in the American tropics
- 2015
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 6:130
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the processes that have generated the latitudinal biodiversity gradient and the continental differences in tropical biodiversity remains a major goal of evolutionary biology. Here we estimate the timing and direction of range shifts of extant flowering plants (angiosperms) between tropical and non-tropical zones, and into and out of the major tropical regions of the world. We then calculate rates of speciation and extinction taking into account incomplete taxonomic sampling. We use a recently published fossil calibrated phylogeny and apply novel bioinformatic tools to code species into user-defined polygons. We reconstruct biogeographic history using stochastic character mapping to compute relative numbers of range shifts in proportion to the number of available lineages through time. Our results, based on the analysis of c. 22,600 species and c. 20 million geo-referenced occurrence records, show no significant differences between the speciation and extinction of tropical and non-tropical angiosperms. This suggests that at least in plants, the latitudinal biodiversity gradient primarily derives from other factors than differential rates of diversification. In contrast, the outstanding species richness found today in the American tropics (the Neotropics), as compared to tropical Africa and tropical Asia, is associated with significantly higher speciation and extinction rates. This suggests an exceedingly rapid evolutionary turnover, i.e., Neotropical species being formed and replaced by one another at unparalleled rates. In addition, tropical America stands out from other continents by having "pumped out" more species than it received through most of the last 66 million years. These results imply that the Neotropics have acted as an engine for global plant diversity. © 2015 Antonelli, Zizka, Silvestro, Scharn, Cascales-Miñana and Bacon.
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| 8. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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Conceptual and empirical advances in Neotropical biodiversity research
- 2018
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 2018:10
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Tidskriftsartikel (refereegranskat)abstract
- The unparalleled biodiversity found in the American tropics (the Neotropics) has attracted the attention of naturalists for centuries. Despite major advances in recent years in our understanding of the origin and diversification of many Neotropical taxa and biotic regions, many questions remain to be answered. Additional biological and geological data are still needed, as well as methodological advances that are capable of bridging these research fields. In this review, aimed primarily at advanced students and early-career scientists, we introduce the concept of "trans-disciplinary biogeography," which refers to the integration of data from multiple areas of research in biology (e.g., community ecology, phylogeography, systematics, historical biogeography) and Earth and the physical sciences (e.g., geology, climatology, palaeontology), as a means to reconstruct the giant puzzle of Neotropical biodiversity and evolution in space and time. We caution against extrapolating results derived from the study of one or a few taxa to convey general scenarios of Neotropical evolution and landscape formation. We urge more coordination and integration of data and ideas among disciplines, transcending their traditional boundaries, as a basis for advancing tomorrow's ground-breaking research. Our review highlights the great opportunities for studying the Neotropical biota to understand the evolution of life.
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| 9. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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Embracing heterogeneity: Coalescing the tree of life and the future of phylogenomics
- 2019
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 2019:2
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Tidskriftsartikel (refereegranskat)abstract
- Building the Tree of Life (ToL) is a major challenge of modern biology, requiring advances in cyberinfrastructure, data collection, theory, and more. Here, we argue that phylogenomics stands to benefit by embracing the many heterogeneous genomic signals emerging from the first decade of large-scale phylogenetic analysis spawned by high-throughput sequencing (HTS). Such signals include those most commonly encountered in phylogenomic datasets, such as incomplete lineage sorting, but also those reticulate processes emerging with greater frequency, such as recombination and introgression. Here we focus specifically on how phylogenetic methods can accommodate the heterogeneity incurred by such population genetic processes; we do not discuss phylogenetic methods that ignore such processes, such as concatenation or supermatrix approaches or supertrees. We suggest that methods of data acquisition and the types of markers used in phylogenomics will remain restricted until a posteriori methods of marker choice are made possible with routine whole-genome sequencing of taxa of interest. We discuss limitations and potential extensions of a model supporting innovation in phylogenomics today, the multispecies coalescent model (MSC). Macroevolutionary models that use phylogenies, such as character mapping, often ignore the heterogeneity on which building phylogenies increasingly rely and suggest that assimilating such heterogeneity is an important goal moving forward. Finally, we argue that an integrative cyberinfrastructure linking all steps of the process of building the ToL, from specimen acquisition in the field to publication and tracking of phylogenomic data, as well as a culture that values contributors at each step, are essential for progress.
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| 10. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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Madagascar's extraordinary biodiversity : Evolution, distribution, and use
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623, s. 962-
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Tidskriftsartikel (refereegranskat)abstract
- Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique " living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.
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