| 31. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 32. |
- Martini, Denise, et al.
(författare)
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Evolution of the “world’s only alpine parrot” : Genomic adaptation or phenotypic plasticity, behaviour and ecology?
- 2021
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:23, s. 6370-6386
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming, in particular in island environments, where opportunities for species to disperse are limited, may become a serious threat to cold adapted alpine species. In order to understand how alpine species may respond to a warming world, we need to understand the drivers that have shaped their habitat specialisation and the evolutionary adaptations that allow them to utilize alpine habitats. The endemic, endangered New Zealand kea (Nestor notabilis) is considered the only alpine parrot in the world. As a species commonly found in the alpine zone it may be highly susceptible to climate warming. But is it a true alpine specialist? Is its evolution driven by adaptation to the alpine zone, or is the kea an open habitat generalist that simply uses the alpine zone to, for example, avoid lower lying anthropogenic landscapes? We use whole genome data of the kea and its close, forest adapted sister species, the kākā (Nestor meridionalis) to reconstruct the evolutionary history of both species and identify the functional genomic differences that underlie their habitat specialisations. Our analyses do not identify major functional genomic differences between kea and kākā in pathways associated with high-altitude. Rather, we found evidence that selective pressures on adaptations commonly found in alpine species are present in both Nestor species, suggesting that selection for alpine adaptations has not driven their divergence. Strongly divergent demographic responses to past climate warming between the species nevertheless highlight potential future threats to kea survival in a warming world.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Mccarroll, Danny, et al.
(författare)
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A critical evaluation of multi-proxy dendroclimatology in northern Finland
- 2011
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 26:1, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- Twentieth-century summer (July-August) temperatures in northern Finland are reconstructed using ring widths, maximum density and stable carbon isotope ratios (delta(13)C) of Scots pine tree rings, and using combinations of these proxies. Verification is based on the coefficient of determination (r(2)), reduction of error (RE) and coefficient of efficiency (CE) statistics. Of the individual proxies, delta(13)C performs best, followed by maximum density. Combining delta(13)C and maximum density strengthens the climate signal but adding ring widths leads to little improvement. Blue intensity, an inexpensive alternative to X-ray densitometry, is shown to perform similarly. Multi-proxy reconstruction of summer temperatures from a single site produces strong correlations with gridded climate data over most of northern Fennoscandia. Since relatively few trees are required (<15) the approach could be applied to long sub-fossil chronologies where replication may be episodically low.
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| 37. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 38. |
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| 39. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 40. |
- Plubell, Deanna L., et al.
(författare)
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Putting Humpty Dumpty Back Together Again : What Does Protein Quantification Mean in Bottom-Up Proteomics? br
- 2022
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:4, s. 891-898
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Tidskriftsartikel (refereegranskat)abstract
- Bottom-up proteomics provides peptide measurements and has beeninvaluable for moving proteomics into large-scale analyses. Commonly, a singlequantitative value is reported for each protein-coding gene by aggregating peptidequantities into protein groups following protein inference or parsimony. However, giventhe complexity of both RNA splicing and post-translational protein modification, it isoverly simplistic to assume that all peptides that map to a singular protein-coding genewill demonstrate the same quantitative response. By assuming that all peptides from aprotein-coding sequence are representative of the same protein, we may miss thediscovery of important biological differences. To capture the contributions of existingproteoforms, we need to reconsider the practice of aggregating protein values to a singlequantity per protein-coding gene.
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