Tor Hervig
Haukeland University Hospital
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Publication
Featured researches published by Tor Hervig.
Nature | 2016
Swapan Mallick; Heng Li; Mark Lipson; Iain Mathieson; Melissa Gymrek; Fernando Racimo; Mengyao Zhao; Niru Chennagiri; Arti Tandon; Pontus Skoglund; Iosif Lazaridis; Sriram Sankararaman; Qiaomei Fu; Nadin Rohland; Gabriel Renaud; Yaniv Erlich; Thomas Willems; Carla Gallo; Jeffrey P. Spence; Yun S. Song; Giovanni Poletti; Francois Balloux; George van Driem; Peter de Knijff; Irene Gallego Romero; Aashish R. Jha; Doron M. Behar; Claudio M. Bravi; Cristian Capelli; Tor Hervig
Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Current Biology | 2003
Cristian Capelli; Nicola Redhead; Julia K. Abernethy; Fiona Gratrix; James F. Wilson; Torolf Moen; Tor Hervig; Martin B. Richards; Michael P. H. Stumpf; Peter A. Underhill; Paul Bradshaw; Alom Shaha; Mark G. Thomas; Neal Bradman; David B. Goldstein
The degree of population replacement in the British Isles associated with cultural changes has been extensively debated. Recent work has demonstrated that comparisons of genetic variation in the British Isles and on the European Continent can illuminate specific demographic processes in the history of the British Isles. For example, Wilson et al. used the similarity of Basque and Celtic Y chromosomes to argue for genetic continuity from the Upper Palaeolithic to the present in the paternal history of these populations (see also ). Differences in the Y chromosome composition of these groups also suggested genetic signatures of Norwegian influence in the Orkney Islands north of the Scottish mainland, an important center of Viking activities between 800 and 1300 A.D. More recently, Weale et al. argued for substantial Anglo-Saxon male migration into central England based on the analysis of eight British sample sets collected on an east-west transect across England and Wales. To provide a more complete assessment of the paternal genetic history of the British Isles, we have compared the Y chromosome composition of multiple geographically distant British sample sets with collections from Norway (two sites), Denmark, and Germany and with collections from central Ireland, representing, respectively, the putative invading and the indigenous populations. By analyzing 1772 Y chromosomes from 25 predominantly small urban locations, we found that different parts of the British Isles have sharply different paternal histories; the degree of population replacement and genetic continuity shows systematic variation across the sampled areas.
Science | 2015
Peter H. Sudmant; Swapan Mallick; Bradley J. Nelson; Fereydoun Hormozdiari; Niklas Krumm; John Huddleston; Bradley P. Coe; Carl Baker; Michael J. Bamshad; Lynn B. Jorde; Olga L. Posukh; Hovhannes Sahakyan; W. Scott Watkins; Levon Yepiskoposyan; M. Syafiq Abdullah; Claudio M. Bravi; Cristian Capelli; Tor Hervig; Joseph Wee; Chris Tyler-Smith; George van Driem; Irene Gallego Romero; Aashish R. Jha; Sena Karachanak-Yankova; Draga Toncheva; David Comas; Brenna M. Henn; Toomas Kivisild; Andres Ruiz-Linares; Antti Sajantila
Duplications and deletions in the human genome Duplications and deletions can lead to variation in copy number for genes and genomic loci among humans. Such variants can reveal evolutionary patterns and have implications for human health. Sudmant et al. examined copy-number variation across 236 individual genomes from 125 human populations. Deletions were under more selection, whereas duplications showed more population-specific structure. Interestingly, Oceanic populations retain large duplications postulated to have originated in an ancient Denisovan lineage. Science, this issue 10.1126/science.aab3761 Copy-number variation reveals how selection affects the human genome across the globe. INTRODUCTION Most studies of human genetic variation have focused on single-nucleotide variants (SNVs). However, copy-number variants (CNVs) affect more base pairs of DNA among humans, and yet our understanding of CNV diversity among human populations is limited. RATIONALE We aimed to understand the pattern, selection, and diversity of copy-number variation by analyzing deeply sequenced genomes representing the diversity of all humans. We compared the selective constraints of deletions versus duplications to understand population stratification in the context of the ancestral human genome and to assess differences in CNV load between African and non-African populations. RESULTS We sequenced 236 individual genomes from 125 distinct human populations and identified 14,467 autosomal CNVs and 545 X-linked CNVs with a sequence read-depth approach. Deletions exhibit stronger selective pressure and are better phylogenetic markers of population relationships than duplication polymorphisms. We identified 1036 population-stratified copy-number–variable regions, 295 of which intersect coding regions and 199 of which exhibit extreme signatures of differentiation. Duplicated loci were 1.8-fold more likely to be stratified than deletions but were poorly correlated with flanking genetic diversity. Among these, we highlight a duplication polymorphism restricted to modern Oceanic populations yet also present in the genome of the archaic Denisova hominin. This 225–kilo–base pair (kbp) duplication includes two microRNA genes and is almost fixed among human Papuan-Bougainville genomes. The data allowed us to reconstruct the ancestral human genome and create a more accurate evolutionary framework for the gain and loss of sequences during human evolution. We identified 571 loci that segregate in the human population and another 2026 loci of fixed-copy 2 in all human genomes but absent from the reference genome. The total deletion and duplication load between African and non-African population groups showed no difference after we account for ancestral sequences missing from the human reference. However, we did observe that the relative number of base pairs affected by CNVs compared to single-nucleotide polymorphisms is higher among non-Africans than Africans. CONCLUSION Deletions, duplications, and CNVs have shaped, to different extents, the genetic diversity of human populations by the combined forces of mutation, selection, and demography. Figure Global human CNV diversity and archaic introgression of a chromosome 16 duplication. (Left) The geographic coordinates of populations sampled are indicated on a world map (colored dots). The pie charts show the continental population allele frequency of a single ~225-kbp duplication polymorphism found exclusively among Oceanic populations and an archaic Denisova. (Right) The ancestral structure of this duplication locus (1) and the Denisova duplication structure (2) are shown in relation to their position on chromosome 16. We estimate that the duplication emerged ~440 thousand years ago (ka) in the Denisova and then introgressed into ancestral Papuan populations ~40 ka. In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide–variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.
Blood | 2008
Nancy M. Heddle; Richard J. Cook; Alan Tinmouth; C. Tom Kouroukis; Tor Hervig; Ellen Klapper; Joseph Brandwein; Zbigniew M. Szczepiorkowski; James P. AuBuchon; Rebecca Barty; Ker Ai Lee
A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding > or = grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group (relative risk [RR], 1.052; 95% confidence interval [CI], 0.737-1.502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on (http://www.clinicaltrials.gov) as NCT00420914.
Transfusion | 2008
Jean-Claude Osselaer; N. Messe; Tor Hervig; José Luis Bueno; Emma Castro; Aurora Espinosa; Patrizia Accorsi; Klaus Junge; Michele Jacquet; Jocelyne Flament; Laurence Corash
BACKGROUND: Inactivation of pathogens and white blood cells in platelet (PLT) components with amotosalen and UVA light (INTERCEPT, Cerus Europe BV) has entered clinical practice in European blood centers. A prospective cohort study was implemented to characterize the safety profile of this new PLT component in a broad patient population.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES , 279 (1730) pp. 884-892. (2012) | 2012
Gbj Busby; Francesca Brisighelli; Paula Sánchez-Diz; E Ramos-Luis; Conrado Martinez-Cadenas; Mark G. Thomas; Daniel G. Bradley; Leonor Gusmão; Bruce Winney; Walter F. Bodmer; M Vennemann; Coia; Francesca Scarnicci; Sergio Tofanelli; Giuseppe Vona; Rafał Płoski; C Vecchiotti; Tatijana Zemunik; Igor Rudan; S Karachanak; Draga Toncheva; Paolo Anagnostou; Gianmarco Ferri; C Rapone; Tor Hervig; Torolf Moen; James F. Wilson; Cristian Capelli
Recently, the debate on the origins of the major European Y chromosome haplogroup R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins to the notion of a younger Neolithic spread of these chromosomes from the Near East. Here, we address this debate by investigating frequency patterns and diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our analysis reveals no geographical trends in diversity, in contradiction to expectation under the Neolithic hypothesis, and suggests an alternative explanation for the apparent cline in diversity recently described. We further investigate the young, STR-based time to the most recent common ancestor estimates proposed so far for R-M269-related lineages and find evidence for an appreciable effect of microsatellite choice on age estimates. As a consequence, the existing data and tools are insufficient to make credible estimates for the age of this haplogroup, and conclusions about the timing of its origin and dispersal should be viewed with a large degree of caution.
Transfusion | 2007
Torunn O. Apelseth; Øystein Bruserud; Tore Wentzel-Larsen; Anne M. Bakken; Solfrid Bjørsvik; Tor Hervig
BACKGROUND: Photochemical treatment (PCT) prevents replication of pathogens in platelet concentrates (PCs) by cross‐linking nucleic acids and thus affects all cells containing DNA or RNA.
Transfusion | 2006
Torunn O. Apelseth; Tor Hervig; Tore Wentzel-Larsen; Øystein Bruserud
BACKGROUND: Photochemical treatment (PCT) for pathogen reduction of platelet concentrates (PCs) affects all cells containing DNA and/or RNA. Soluble mediators, which may cause transfusion reactions, are determined by the balance between secretion and/or cell destruction and binding and/or degradation.
Shock | 2014
Donald H. Jenkins; Joseph F. Rappold; John F. Badloe; Olle Berséus; Col Lorne Blackbourne; Karim Brohi; Frank K. Butler; Ltc Andrew P Cap; Mitchell J. Cohen; Ross Davenport; Marc DePasquale; Heidi Doughty; Elon Glassberg; Tor Hervig; Timothy J. Hooper; Rosemary A. Kozar; Marc Maegele; Ernest E. Moore; Alan Murdock; Paul M. Ness; Shibani Pati; Col Todd Rasmussen; Anne Sailliol; Martin A. Schreiber; Geir Arne Sunde; Leo M G Van De Watering; Kevin R. Ward; Richard B. Weiskopf; Nathan J. White; Geir Strandenes
ABSTRACT The Trauma Hemostasis and Oxygenation Research Network held its third annual Remote Damage Control Resuscitation Symposium in June 2013 in Bergen, Norway. The Trauma Hemostasis and Oxygenation Research Network is a multidisciplinary group of investigators with a common interest in improving outcomes and safety in patients with severe traumatic injury. The network’s mission is to reduce the risk of morbidity and mortality from traumatic hemorrhagic shock, in the prehospital phase of resuscitation through research, education, and training. The concept of remote damage control resuscitation is in its infancy, and there is a significant amount of work that needs to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical in these patients. If shock and coagulopathy can be rapidly identified and minimized before hospital admission, this will very likely reduce morbidity and mortality. This position statement begins to standardize the terms used, provides an acceptable range of therapeutic options, and identifies the major knowledge gaps in the field.
Shock | 2014
Heather F. Pidcoke; Philip C. Spinella; Anand K. Ramasubramanian; Geir Strandenes; Tor Hervig; Paul M. Ness; Andrew P. Cap
Abstract This review is a synopsis of the decisions that shaped global policy on platelet (PLT) storage temperature and a focused appraisal of the literature on which those discussions were based. We hypothesize that choices were centered on optimization of preventive PLT transfusion strategies, possibly to the detriment of the therapeutic needs of acutely bleeding patients. Refrigerated PLTs are a better hemostatic product, and they are safer in that they are less prone to bacterial contamination. They were abandoned during the 1970s because of the belief that clinically effective PLTs should both be hemostatically functional and survive in circulation for several days as indicated for prophylactic transfusion; however, clinical practice may be changing. Data from two randomized controlled trials bring into question the concept that stable autologous stem cell transplant patients with hypoproliferative thrombocytopenia should continue to receive prophylactic transfusions. At the same time, new findings regarding the efficacy of cold PLTs and their potential role in treating acute bleeding have revived the debate regarding optimal PLT storage temperature. In summary, a “one-size-fits-all” strategy for PLT storage may not be adequate, and a reexamination of whether cold-stored PLTs should be offered as a widely available therapeutic product may be indicated.