The genetic basis of complex traits studied via analysis of evolve and resequence experiments

By: Material type: TextTextPublication details: Institute of Science and Technology Austria 2022Online resources:
Contents:
Abstract
Acknowledgments
About the Author
List of Collaborators and Publications
Table of Contents
List of Figures
List of Tables
1 Introduction
2 Analysis of an Evolve and Resequence Experiment in Mice
3 Association between SNPs and Hapiotypes
4 Analysis of an Evolve and Resequence Experiment in Drosophila
5 Conclusion
Bibliography
Summary: In evolve and resequence experiments, a population is sequenced, subjected to selection and then sequenced again, so that genetic changes before and after selection can be observed at the genetic level. Here, I use these studies to better understand the genetic basis of complex traits - traits which depend on more than a few genes. In the first chapter, I discuss the first evolve and resequence experiment, in which a population of mice, the so-called "Longshanks" mice, were selected for tibia length while their body mass was kept constant. The full pedigree is known. We observed a selection response on all chromosomes and used the infinitesimal model with linkage, a model which assumes an infinite number of genes with infinitesimally small effect sizes, as a null model. Results implied a very polygenic basis with a few loci of major effect standing out and changing in parallel. There was large variability between the different chromosomes in this study, probably due to LD. In chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency based summary statistic, giving an equation based on the initial allele frequencies, average pairwise LD, and the first four moments of the haplotype block copy number distribution. I describe this distribution by referring back to the founder generation. I then demonstrate how to infer selection via a maximum likelihood scheme on the example of a single locus and discuss how to extend this to more realistic scenarios. In chapter three, I discuss the second evolve and resequence experiment, in which a small population of Drosophila melanogaster was selected for increased pupal case size over 6 generations. The experiment was highly replicated with 27 lines selected within family and a known pedigree. We observed a phenotypic selection response of over one standard deviation. I describe the patterns in allele frequency data, including allele frequency changes and patterns of heterozygosity, and give ideas for future work.
List(s) this item appears in: ISTA Thesis

Thesis

Abstract

Acknowledgments

About the Author

List of Collaborators and Publications

Table of Contents

List of Figures

List of Tables

1 Introduction

2 Analysis of an Evolve and Resequence Experiment in Mice

3 Association between SNPs and Hapiotypes

4 Analysis of an Evolve and Resequence Experiment in Drosophila

5 Conclusion

Bibliography

In evolve and resequence experiments, a population is sequenced, subjected to selection and then sequenced again, so that genetic changes before and after selection can be observed at the genetic level. Here, I use these studies to better understand the genetic basis of complex traits - traits which depend on more than a few genes. In the first chapter, I discuss the first evolve and resequence experiment, in which a population of mice, the so-called "Longshanks" mice, were selected for tibia length while their body mass was kept constant. The full pedigree is known. We observed a selection response on all chromosomes and used the infinitesimal model with linkage, a model which assumes an infinite number of genes with infinitesimally small effect sizes, as a null model. Results implied a very polygenic basis with a few loci of major effect standing out and changing in parallel. There was large variability between the different chromosomes in this study, probably due to LD. In chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency based summary statistic, giving an equation based on the initial allele frequencies, average pairwise LD, and the first four moments of the haplotype block copy number distribution. I describe this distribution by referring back to the founder generation. I then demonstrate how to infer selection via a maximum likelihood scheme on the example of a single locus and discuss how to extend this to more realistic scenarios. In chapter three, I discuss the second evolve and resequence experiment, in which a small population of Drosophila melanogaster was selected for increased pupal case size over 6 generations. The experiment was highly replicated with 27 lines selected within family and a known pedigree. We observed a phenotypic selection response of over one standard deviation. I describe the patterns in allele frequency data, including allele frequency changes and patterns of heterozygosity, and give ideas for future work.

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