| 1. |
- Chami, Nathalie, et al.
(author)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Journal article (peer-reviewed)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 2. |
- Eicher, John D., et al.
(author)
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Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals
- 2016
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 40-55
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Journal article (peer-reviewed)abstract
- Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
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| 3. |
- Kawakami, Takeshi, et al.
(author)
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Estimation of linkage disequilibrium and interspecific gene flow in Ficedula flycatchers by a newly developed 50k single-nucleotide polymorphism array
- 2014
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 14:6, s. 1248-1260
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Journal article (peer-reviewed)abstract
- With the access to draft genome sequence assemblies and whole-genome resequencing data from population samples, molecular ecology studies will be able to take truly genome-wide approaches. This now applies to an avian model system in ecological and evolutionary research: Old World flycatchers of the genus Ficedula, for which we recently obtained a 1.1Gb collared flycatcher genome assembly and identified 13 million single-nucleotide polymorphism (SNP)s in population resequencing of this species and its sister species, pied flycatcher. Here, we developed a custom 50K Illumina iSelect flycatcher SNP array with markers covering 30 autosomes and the Z chromosome. Using a number of selection criteria for inclusion in the array, both genotyping success rate and polymorphism information content (mean marker heterozygosity=0.41) were high. We used the array to assess linkage disequilibrium (LD) and hybridization in flycatchers. Linkage disequilibrium declined quickly to the background level at an average distance of 17kb, but the extent of LD varied markedly within the genome and was more than 10-fold higher in genomic islands' of differentiation than in the rest of the genome. Genetic ancestry analysis identified 33 F-1 hybrids but no later-generation hybrids from sympatric populations of collared flycatchers and pied flycatchers, contradicting earlier reports of backcrosses identified from much fewer number of markers. With an estimated divergence time as recently as <1Ma, this suggests strong selection against F-1 hybrids and unusually rapid evolution of reproductive incompatibility in an avian system.
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| 4. |
- Qvarnström, Anna, et al.
(author)
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Speciation in Ficedula flycatchers
- 2010
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In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 365:1547, s. 1841-1852
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Research review (peer-reviewed)abstract
- Speciation in animals often requires that population divergence goes through three major evolutionary stages, i.e. ecological divergence, development of sexual isolation and the build-up of genetic incompatibility. There is theoretical consensus regarding favourable conditions required for speciation to reach its final and irreversible stage, but empirical tests remain rare. Here, we review recent research on processes of speciation, based on studies in hybrid zones between collared (Ficedula albicollis) and pied flycatchers (Ficedula hypoleuca). A major advantage of this study system is that questions concerning all three major sources of reproductive isolation and their interconnections can be addressed. We conclude that (i) ecological divergence is caused by divergence in life-history traits, (ii) females prefer mates of their own species based on differences in both plumage and song characteristics, (iii) male plumage characteristics have diverged but their song has converged in sympatry, (iv) there is genetic incompatibility in accordance with Haldane's rule, and (v) the Z-chromosome appears to be a hotspot for genes involved in sexual isolation and genetic incompatibility. We discuss how identification of the genes underlying the three major sources of reproductive isolation can be used to draw conclusions about links between the processes driving their evolution.
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| 5. |
- Rice, Amber M., et al.
(author)
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A guide to the genomics of ecological speciation in natural animal populations
- 2011
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 14:1, s. 9-18
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Journal article (peer-reviewed)abstract
- Interest in ecological speciation is growing, as evidence accumulates showing that natural selection can lead to rapid divergence between subpopulations. However, whether and how ecological divergence can lead to the buildup of reproductive isolation remains under debate. What is the relative importance of natural selection vs. neutral processes? How does adaptation generate reproductive isolation? Can ecological speciation occur despite homogenizing gene flow? These questions can be addressed using genomic approaches, and with the rapid development of genomic technology, will become more answerable in studies of wild populations than ever before. In this article, we identify open questions in ecological speciation theory and suggest useful genomic methods for addressing these questions in natural animal populations. We aim to provide a practical guide for ecologists interested in incorporating genomic methods into their research programs. An increased integration between ecological research and genomics has the potential to shed novel light on the origin of species.
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| 6. |
- Rice, Amber M., et al.
(author)
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Optimizing the trade-off between offspring number and quality in unpredictable environments: Testing the role of differential androgen transfer to collared flycatcher eggs
- 2013
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In: Hormones and Behavior. - : Elsevier BV. - 1095-6867 .- 0018-506X. ; 63:5, s. 813-822
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Journal article (peer-reviewed)abstract
- According to the brood reduction hypothesis, parents adjust their brood size in response to current environmental conditions. When resources are abundant, parents can successfully raise all hatched offspring, but when resources are scarce, brood reduction, i.e., the sacrifice of some siblings to secure the quality of a subset of offspring, may maximize fitness. Differential transfer of maternal androgens is one potential proximate mechanism through which female birds may facilitate brood reduction because it may alter the relative competitive ability of sibling nestlings. We tested the hypothesis that female collared flycatchers (Ficedula albicollis) manipulate sibling competition by transferring less androgens to eggs late in the laying sequence. We experimentally elevated androgen levels in i) whole clutches and ii) only the two last laid eggs, and compared growth and begging behavior of offspring from these treatments with a control treatment. By using three treatments and video assessment of begging, we examined the effects of within-clutch patterns of yolk androgen transfer on levels of sibling competition in situ. When androgens were elevated in only the two last laid eggs, begging was more even among siblings compared to control nests. We also found that female nestlings receiving additional yolk androgens showed higher mass gain later in the breeding season, while their male counterparts did not. Our results suggest that females may improve reproductive success in unpredictable environments by altering within-clutch patterns of yolk androgen transfer. We discuss the possibility that life-history divergence between the co-occurring collared and pied flycatcher (Ficedula hypoleuca) is amplified by patterns of yolk androgen transfer. (C) 2013 Elsevier Inc. All rights reserved.
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| 7. |
- Rice, Amber M., et al.
(author)
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Parallel evolution and ecological selection : replicated character displacement in spadefoot toads
- 2009
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 276:1676, s. 4189-4196
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Journal article (peer-reviewed)abstract
- Ecological character displacement-trait evolution stemming from selection to lessen resource competition between species-is most often inferred from a pattern in which species differ in resource-use traits in sympatry but not in allopatry, and in which sympatric populations within each species differ from conspecific allopatric populations. Yet, without information on population history, the presence of a divergent phenotype in multiple sympatric populations does not necessarily imply that there has been repeated evolution of character displacement. Instead, such a pattern may arise if there has been character displacement in a single ancestral population, followed by gene flow carrying the divergent phenotype into multiple, derived, sympatric populations. Here, we evaluate the likelihood of such historical events versus ongoing ecological selection in generating divergence in trophic morphology between multiple populations of spadefoot toad (Spea multiplicata) tadpoles that are in sympatry with a heterospecific and those that are in allopatry. We present both phylogenetic and population genetic evidence indicating that the same divergent trait, which minimizes resource competition with the heterospecific, has arisen independently in multiple sympatric populations. These data, therefore, provide strong indirect support for competition's role in divergent trait evolution.
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| 8. |
- Vallin, Niclas, et al.
(author)
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Combined effects of interspecific competition and hybridization impede local coexistence of Ficedula flycatchers
- 2012
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In: Evolutionary Ecology. - : Springer Science and Business Media LLC. - 0269-7653 .- 1573-8477. ; 26:4, s. 927-942
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Journal article (peer-reviewed)abstract
- At secondary contact closely related species may both compete over similar resources and/or hybridize. Simulation models suggest that hybridization increases the risk of extinction beyond the risk resulting from interspecific competition alone, but such combined effects are rarely studied empirically. Here, we use detailed records on pairing patterns, breeding success, local recruitment and immigration collected during 8 years (2002-2009) to investigate the underlying mechanism of the rapid displacement of pied flycatchers by collared flycatchers on the Swedish island of A-land. We found no differences in average reproductive success or reproductive lifespan between the two species. However, we show that young male pied flycatchers failed to establish new territories as the density of male collared flycatchers increased. In addition, as the relative frequency of collared flycatchers increased, the risk of hybridization dramatically increased for female pied flycatchers, which speeds up the exclusion process since there is a high fitness cost associated with hybridization between the two species. In a nearby control area, within the same island, where pied flycatchers breed in the absence of collared flycatchers, no decline in the number of breeding pairs was observed during the same period of time. Our results demonstrate the crucial importance of studying the combined effects of various types of heterospecific interactions to understand and predict the ecological and evolutionary implications of secondary contact between congeneric species. These findings are particularly interesting in the light of recent climate change since the expected range shifts of many taxa will increase competitive and sexual interactions between previously separated species.
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| 9. |
- Vallin, Niclas, et al.
(author)
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Positive feedback between ecological and reproductive character displacement in a young avian hybrid zone
- 2012
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In: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 66:4, s. 1167-1179
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Journal article (peer-reviewed)abstract
- Character displacement can reduce costly interspecific interactions between young species. We investigated the mechanisms behind divergence in three key traits—breeding habitat choice, timing of breeding, and plumage coloration—in Ficedula flycatchers. We found that male pied flycatchers became expelled from the preferred deciduous habitat into mixed forest as the superior competitor, collared flycatchers, increased in numbers. The peak in food abundance differs between habitats, and the spatial segregation was paralleled by an increased divergence in timing of breeding between the two species. Male pied flycatchers vary from brown to black with brown coloration being more frequent in sympatry with collared flycatchers, a pattern often proposed to result from selection against hybridization, that is, reinforcement. In contrast to this view, we show that brown male pied flycatchers more often hybridize than black males. Male pied flycatcher plumage coloration influenced the territory obtained in areas of co-occurrence with collared flycatchers, and brown male pied flycatchers experienced higher relative fitness than black males when faced with heterospecific competition. We suggest that allopatric divergence in resource defense ability causes a feedback loop at secondary contact where male pied flycatchers with the most divergent strategy compared to collared flycatchers are favored by selection.
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| 10. |
- Ålund, Murielle, et al.
(author)
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Low fertility of wild hybrid male flycatchers despite recent divergence
- 2013
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In: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 9:3
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Journal article (peer-reviewed)abstract
- Postzygotic isolation may be important for maintaining species boundaries, particularly when premating barriers are incomplete. Little is known about the course of events leading from minor environmental mismatches affecting hybrid fitness to severe genetic incompatibilities causing sterility or inviability. We investigated whether reduced reproductive success of hybrid males was caused by suboptimal sperm traits or by more severe genetic incompatibilities in a hybrid zone of pied (Ficedula hypoleuca) and collared flycatchers (F. albicollis) on the island of Oland, Sweden. About 4 per cent hybridization is observed in this population and all female hybrids are sterile. We found no sperm in the ejaculates of most sampled hybrid males, and sperm with abnormal morphology in two hybrids. Furthermore, none of the hybrids sired any offspring because of high levels of hatching failure and extra-pair paternity in their nests. These results from a natural hybrid zone suggest that the spermatogenesis of hybrid males may become disrupted despite little genetic divergence between the parental species.
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