| 1. |
- Hedrick, Philip W., et al.
(författare)
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Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves
- 2017
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Ingår i: Journal of Heredity. - : OXFORD UNIV PRESS INC. - 0022-1503 .- 1465-7333. ; 108:2, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding.
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| 2. |
- Kardos, Marty, et al.
(författare)
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Genomic consequences of intensive inbreeding in an isolated wolf population
- 2018
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:1, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- Inbreeding (mating between relatives) is a major concern for conservation as it decreases individual fitness and can increase the risk of population extinction. We used whole-genome resequencing of 97 grey wolves (Canis lupus) from the highly inbred Scandinavian wolf population to identify 'identical-by-descent' (IBD) chromosome segments as runs of homozygosity (ROH). This gave the high resolution required to precisely measure realized inbreeding as the IBD fraction of the genome in ROH (F-ROH). We found a striking pattern of complete or near-complete homozygosity of entire chromosomes in many individuals. The majority of individual inbreeding was due to long IBD segments (>5 cM) originating from ancestors <= 10 generations ago, with 10 genomic regions showing very few ROH and forming candidate regions for containing loci contributing strongly to inbreeding depression. Inbreeding estimated with an extensive pedigree (F-P) was strongly correlated with realized inbreeding measured with the entire genome (r(2) = 0.86). However, inbreeding measured with the whole genome was more strongly correlated with multi-locus heterozygosity estimated with as few as 500 single nucleotide polymorphisms, and with F-ROH estimated with as few as 10,000 single nucleotide polymorphisms, than with F-P. These results document in fine detail the genomic consequences of intensive inbreeding in a population of conservation concern.
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| 3. |
- Kardos, Marty, et al.
(författare)
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Genomics advances the study of inbreeding depression in the wild
- 2016
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 9:10, s. 1205-1218
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Forskningsöversikt (refereegranskat)abstract
- Inbreeding depression (reduced fitness of individuals with related parents) has long been a major focus of ecology, evolution, and conservation biology. Despite decades of research, we still have a limited understanding of the strength, underlying genetic mechanisms, and demographic consequences of inbreeding depression in the wild. Studying inbreeding depression in natural populations has been hampered by the inability to precisely measure individual inbreeding. Fortunately, the rapidly increasing availability of high-throughput sequencing data means it is now feasible to measure the inbreeding of any individual with high precision. Here, we review how genomic data are advancing our understanding of inbreeding depression in the wild. Recent results show that individual inbreeding and inbreeding depression can be measured more precisely with genomic data than via traditional pedigree analysis. Additionally, the availability of genomic data has made it possible to pinpoint loci with large effects contributing to inbreeding depression in wild populations, although this will continue to be a challenging task in many study systems due to low statistical power. Now that reliably measuring individual inbreeding is no longer a limitation, a major focus of future studies should be to more accurately quantify effects of inbreeding depression on population growth and viability.
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| 4. |
- Kardos, Marty, et al.
(författare)
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Inferring Individual Inbreeding and Demographic History from Segments of Identity by Descent in Ficedula Flycatcher Genome Sequences
- 2017
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Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 205:3, s. 1319-1334
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Tidskriftsartikel (refereegranskat)abstract
- Individual inbreeding and historical demography can be estimated by analyzing runs of homozygosity (ROH), which are indicative of chromosomal segments of identity by descent (IBD). Such analyses have so far been rare in natural populations due to limited genomic resources. We analyzed ROH in whole genome sequences from 287 Ficedula flycatchers representing four species, with the objectives of evaluating the causes of genome-wide variation in the abundance of ROH and inferring historical demography. ROH were clearly more abundant in genomic regions with low recombination rate. However, this pattern was substantially weaker when ROH were mapped using genetic rather than physical single nucleotide polymorphism (SNP) coordinates in the genome. Empirical results and simulations suggest that high ROH abundance in regions of low recombination was partly caused by increased power to detect the very long IBD segments typical of regions with a low recombination rate. Simulations also showed that hard selective sweeps (but not soft sweeps or background selection) likely contributed to variation in the abundance of ROH across the genome. Comparisons of the abundance of ROH among several study populations indicated that the Spanish pied flycatcher population had the smallest historical effective population size (Ne) for this species, and that a putatively recently founded island (Baltic) population had the smallest historical Ne among the collared flycatchers. Analysis of pairwise IBD in Baltic collared flycatchers indicated that this population was founded,60 generations ago. This study provides a rare genomic glimpse into demographic history and the mechanisms underlying the genome-wide distribution of ROH.
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| 5. |
- Kardos, Marty, et al.
(författare)
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Measuring individual inbreeding in the age of genomics : marker-based measures are better than pedigrees
- 2015
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 115:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- Inbreeding (mating between relatives) can dramatically reduce the fitness of offspring by causing parts of the genome to be identical by descent. Thus, measuring individual inbreeding is crucial for ecology, evolution and conservation biology. We used computer simulations to test whether the realized proportion of the genome that is identical by descent (IBDG) is predicted better by the pedigree inbreeding coefficient (F-P) or by genomic (marker-based) measures of inbreeding. Genomic estimators of IBDG included the increase in individual homozygosity relative to mean Hardy-Weinberg expected homozygosity (F-H), and two measures (F-ROH and F-E) that use mapped genetic markers to estimate IBDG. IBDG was more strongly correlated with F-H, F-E and F-ROH than with F-P across a broad range of simulated scenarios when thousands of SNPs were used. For example, IBDG was more strongly correlated with F-ROH, F-H and F-E (estimated with >= 10 000 SNPs) than with F-P (estimated with 20 generations of complete pedigree) in populations with a recent reduction in the effective populations size (from N-e=500 to N-e=75). F-ROH, F-H and F-E generally explained 490% of the variance in IBDG (among individuals) when 35 K or more SNPs were used. F-P explained <80% of the variation in IBDG on average in all simulated scenarios, even when pedigrees included 20 generations. Our results demonstrate that IBDG can be more precisely estimated with large numbers of genetic markers than with pedigrees. We encourage researchers to adopt genomic marker-based measures of IBDG as thousands of loci can now be genotyped in any species.
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| 6. |
- Kardos, Marty, et al.
(författare)
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Whole-genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations
- 2016
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 16:3, s. 727-741
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Tidskriftsartikel (refereegranskat)abstract
- Dissecting the genetic basis of phenotypic variation in natural populations is a long-standing goal in evolutionary biology. One open question is whether quantitative traits are determined only by large numbers of genes with small effects, or whether variation also exists in large-effect loci. We conducted genomewide association analyses of forehead patch size (a sexually selected trait) on 81 whole-genome-resequenced male collared flycatchers with extreme phenotypes, and on 415 males sampled independent of patch size and genotyped with a 50K SNP chip. No SNPs were genomewide statistically significantly associated with patch size. Simulation-based power analyses suggest that the power to detect large-effect loci responsible for 10% of phenotypic variance was <0.5 in the genome resequencing analysis, and <0.1 in the SNP chip analysis. Reducing the recombination by two-thirds relative to collared flycatchers modestly increased power. Tripling sample size increased power to >0.8 for resequencing of extreme phenotypes (N=243), but power remained <0.2 for the 50K SNP chip analysis (N=1245). At least 1 million SNPs were necessary to achieve power >0.8 when analysing 415 randomly sampled phenotypes. However, power of the 50K SNP chip to detect large-effect loci was nearly 0.8 in simulations with a small effective population size of 1500. These results suggest that reliably detecting large-effect trait loci in large natural populations will often require thousands of individuals and near complete sampling of the genome. Encouragingly, far fewer individuals and loci will often be sufficient to reliably detect large-effect loci in small populations with widespread strong linkage disequilibrium.
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| 7. |
- Kardos, Marty, et al.
(författare)
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Whole-genome resequencing uncovers molecular signatures of natural and sexual selection in wild bighorn sheep
- 2015
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 24:22, s. 5616-5632
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Tidskriftsartikel (refereegranskat)abstract
- The identification of genes influencing fitness is central to our understanding of the genetic basis of adaptation and how it shapes phenotypic variation in wild populations. Here, we used whole-genome resequencing of wild Rocky Mountain bighorn sheep (Ovis canadensis) to >50-fold coverage to identify 2.8 million single nucleotide polymorphisms (SNPs) and genomic regions bearing signatures of directional selection (i.e. selective sweeps). A comparison of SNP diversity between the X chromosome and the autosomes indicated that bighorn males had a dramatically reduced long-term effective population size compared to females. This probably reflects a long history of intense sexual selection mediated by male-male competition for mates. Selective sweep scans based on heterozygosity and nucleotide diversity revealed evidence for a selective sweep shared across multiple populations at RXFP2, a gene that strongly affects horn size in domestic ungulates. The massive horns carried by bighorn rams appear to have evolved in part via strong positive selection at RXFP2. We identified evidence for selection within individual populations at genes affecting early body growth and cellular response to hypoxia; however, these must be interpreted more cautiously as genetic drift is strong within local populations and may have caused false positives. These results represent a rare example of strong genomic signatures of selection identified at genes with known function in wild populations of a nonmodel species. Our results also showcase the value of reference genome assemblies from agricultural or model species for studies of the genomic basis of adaptation in closely related wild taxa.
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| 8. |
- Laikre, Linda, 1960-, et al.
(författare)
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Planned cull endangers Swedish wolf population
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 377:6602
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Tidskriftsartikel (refereegranskat)abstract
- In May, the Swedish Parliament announced a goal to reduce the Swedish wolf population from about 400 to about 200 individuals (1). This action further threatens this highly endangered population, which is genetically isolated and inbred. Scientific advice for improvements has not been implemented (2, 3).The Swedish Parliament proposed this drastic cull at a time when biodiversity is a global focus. The 50-year anniversary of the first UN conference on the environment was celebrated in June, and the UN Convention on Biological Diversity (CBD) will soon finalize its global biodiversity framework for 2020 to 2050. Sweden’s actions are inconsistent with the country’s obligations under the CBD and European Union law.Few wild populations are as well studied as the Scandinavian wolf. Genetic monitoring has provided a full pedigree since the population was reestablished in the 1980s after extinction, and the data confirm persisting genetic isolation (4–6). Hunting, conducted both legally and illegally, has prevented population expansion and the influx of genetic variation.Three founders comprised the population’s genetic origin until 2007, and only three more wolves have subsequently contributed genetically to the present population (6). The genetic base is thus extremely narrow, and genomic erosion has been confirmed (7, 8). The average level of inbreeding is similar to the level found in the offspring of two full siblings (6). Inbreeding in this population has been shown to reduce litter size (4). Also, high frequencies of anatomical defects (9) and male reproductive disorders (10) have been observed.To make this population viable, population size and immigration must increase. So far, the population has been too small, and limited immigration followed by inbreeding could lead to extinction, similar to the Isle Royale wolf population (11). The goal should be to recreate a well-connected metapopulation spanning Scandinavia and Finland with a genetically effective population size of over 500, in line with the proposed CBD indicator (12). Considerably more genetic exchange than the current one-migrant-per-generation aim is needed (3).
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| 9. |
- Roffler, Gretchen H., et al.
(författare)
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SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate
- 2016
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 16:5, s. 1147-1164
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding and nearby 5 and 3 untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Oviscanadensis) exon capture data and directly from the domestic sheep genome (Ovisaries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR-based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease-regulating functions (e.g. Ovar-DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene-targeted SNP discovery and subsequent SNP chip genotyping using low-quality samples in a nonmodel species.
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| 10. |
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