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Natural CMT2 variation is associated with genome-wide methylation changes and temperature seasonality.
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2014 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 12Article in journal (Refereed) Published
Description
Abstract [en]

As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach reduces confounding with population structure and increases power compared to standard genome-wide association methods. Sixteen novel loci were found, including an association between Chromomethylase 2 (CMT2) and temperature seasonality where the genome-wide CHH methylation was different for the group of accessions carrying the plastic allele. Cmt2 mutants were shown to be more tolerant to heat-stress, suggesting genetic regulation of epigenetic modifications as a likely mechanism underlying natural adaptation to variable temperatures, potentially through differential allelic plasticity to temperature-stress.

Place, publisher, year, edition, pages
2014. Vol. 10, no 12
National Category
Natural Sciences
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:uu:diva-294203DOI: 10.1371/journal.pgen.1004842PubMedID: 25503602OAI: oai:DiVA.org:uu-294203DiVA: diva2:929257
Available from: 2016-05-18 Created: 2016-05-18 Last updated: 2016-11-30
In thesis
1. Complex Trait Genetics: Beyond Additivity
Open this publication in new window or tab >>Complex Trait Genetics: Beyond Additivity
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The link between the genotype and the phenotype of an organism is immensely complex. Despite this it can, to a great extent, be captured using models that assume that gene variants combine their effects in an additive manner. This thesis explores aspects of genetics that cannot be fully captured using such additive models. Using experimental data from three different model organisms, I study two phenomena that fall outside of the additive paradigm: genetic interactions and genetic variance heterogeneity.

Using the model plant Arabidopsis thaliana, we show how important biological insights can be reached by exploring loci that display genetic variance heterogeneity. In the first study, this approach identified alleles in the gene CMT2 associated with the climate at sampling locations, suggesting a role in climate adaption. These alleles affected the genome wide methylation pattern, and a complete knock down of this gene increased the plants heat tolerance. In the second study, we demonstrate how the observed genetic variance heterogeneity was the result of the partial linkage of many functional alleles near the gene MOT1, all contributing to Molybdenum levels in the leaves.

Further, we explore genetic interactions using data from dogs and budding yeast (Saccharomyces cerevisiae). In the dog population, two interacting loci were associated with fructosamine levels, a biomarker used to monitor blood glucose. One of the loci displayed the pattern of a selective sweep in some of the studied breeds, suggesting that the interaction is important for the phenotypic breed-differences.

In a cross between two strains of yeast, with the advantage of large population size and nearly equal allele frequencies, we identified large epistatic networks. The networks were largely centered on a number of hub-loci and altogether involved hundreds of genetic interactions. Most network hubs had the ability to either suppress or uncover the phenotypic effects of other loci. Many multi-locus allele combinations resulted in phenotypes that deviated significantly from the expectations, had the loci acted in an additive manner.

Critically, this thesis demonstrates that non-additive genetic mechanisms often need to be considered in order to fully understand the genetics of complex traits. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 45 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1278
Keyword
genetic interactions, epistasis, additivity, GWAS, vGWAS, Genetic mapping, yeast, Arabidopsis Thaliana, dog
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:uu:diva-307837 (URN)978-91-554-9754-5 (ISBN)
Public defence
2017-01-13, B22, BMC, Husarg. 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-12-22 Created: 2016-11-22 Last updated: 2016-12-28

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