1. |
- Pinese, Mark, et al.
(författare)
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The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
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2. |
- Statham, Mark J., et al.
(författare)
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Genetic analysis of European red foxes reveals multiple distinct peripheral populations and central continental admixture
- 2018
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 197, s. 257-266
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Tidskriftsartikel (refereegranskat)abstract
- Temperate terrestrial species in Europe were hypothesized to have been restricted to southern peninsular refugia (Iberia, Italy, Balkans) during the height of the last glacial period. However, recent analyses of fossil evidence indicate that some temperate species existed outside these areas during the last glacial maximum (LGM). Red foxes (Vulpes vulpes) in particular, could have been distributed across the southern half of the continent, potentially forming one continuous population. To investigate these hypotheses, we used 21 nuclear microsatellite loci and two fragments (768 bp) of mitochondrial DNA to characterize the population structure among a continent-wide sample of 288 European red foxes. We tested whether European red foxes clustered into discrete populations corresponding to the hypothetical peninsular refugia. Additionally, we sought to determine if distinct northern populations were formed after post-glacial recolonization. Our results indicated that only the foxes of Iberia appeared to have remained distinct over a considerable period of time (32–104 kya). Spanish red foxes formed their own genotypic cluster; all mtDNA haplotypes were endemic and closely related, and together both the mitochondrial and nuclear datasets indicated this population contributed little to postglacial recolonization of Northern Europe. In contrast, red foxes from Italy and the Balkans contributed significantly to, or were part of, a wider, admixed population stretching across mid-latitude Europe. In Northern Europe, we identified a Scandinavian population that had an ancestral relationship with red foxes to the south, and a more recent relationship with those to the east, in Russia. We also resolved two distinct populations on the islands of Ireland and Britain that had been separated from one another, and from those on the continent, since the late Pleistocene/mid Holocene (∼4–24 kya).
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3. |
- McDevitt, Allan D., et al.
(författare)
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Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe
- 2022
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 31:3, s. 993-1006
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Tidskriftsartikel (refereegranskat)abstract
- Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species.
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4. |
- Norén, Karin, et al.
(författare)
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Genetic footprints reveal geographic patterns of expansion in Fennoscandian red foxes
- 2015
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:9, s. 3299-3312
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Tidskriftsartikel (refereegranskat)abstract
- Population expansions of boreal species are among the most substantial ecological consequences of climate change, potentially transforming both structure and processes of northern ecosystems. Despite their importance, little is known about expansion dynamics of boreal species. Red foxes (Vulpes vulpes) are forecasted to become a keystone species in northern Europe, a process stemming from population expansions that began in the 19th century. To identify the relative roles of geographic and demographic factors and the sources of northern European red fox population expansion, we genotyped 21 microsatellite loci in modern and historical (1835–1941) Fennoscandian red foxes. Using Bayesian clustering and Bayesian inference of migration rates, we identified high connectivity and asymmetric migration rates across the region, consistent with source-sink dynamics, whereby more recently colonized sampling regions received immigrants from multiple sources. There were no clear clines in allele frequency or genetic diversity as would be expected from a unidirectional range expansion from south to north. Instead, migration inferences, demographic models and comparison to historical red fox genotypes suggested that the population expansion of the red fox is a consequence of dispersal from multiple sources, as well as in situ demographic growth. Together, these findings provide a rare glimpse into the anatomy of a boreal range expansion and enable informed predictions about future changes in boreal communities.
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5. |
- Wallén, Johan, et al.
(författare)
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Multiple recolonization routes towards the north : population history of the Fennoscandian red fox (Vulpes vulpes)
- 2018
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Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 124:4, s. 621-632
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the response of boreal species to past climate warming can help to predict future responses to climate change. In the Northern Hemisphere, the distribution and abundance of northern populations have been influenced by previous glaciations. In this study, we investigated the population history of the Fennoscandian red fox (Vulpes vulpes), which is a generalist carnivore currently undergoing range expansion in the tundra ecosystem. By analysing a 696 bp sequence of the mitochondrial DNA (N = 259) and two Y chromosome-specific microsatellite loci (N = 120), we specifically investigated where the red fox survived the Last Glacial Maximum and how Fennoscandia was recolonized. There was high genetic continuity across most of Fennoscandia, and we identified at least two recolonization pathways: one from continental Europe and one from the northeast (Siberia). Mitochondrial haplotype diversity displayed a significant decline with increasing latitude, consistent with expectations of unidirectional colonization. Each region displayed signatures of recent demographic and/or range expansions. For Finland, an additional recolonization route was suggested from the mismatch distribution analysis and identification of novel haplotypes. We concluded that, as with many boreal generalist species, the Fennoscandian red fox originates from multiple refugia, suggesting that it has benefited from diverse evolutionary histories, potentially enhancing its tolerance to different habitat conditions.
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