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Japanese courage: a genetic analysis of complex traits in medaka fish and humans



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Brettell, Ian 


This thesis primarily explores how an individual's genes interact with the genes of their social companions to create differences in behaviour, using the Japanese medaka fish as a model organism. Chapter 1 sets out the introduction to the diverse topics covered in this thesis, and is followed by five substantive chapters.

Chapter 2 describes several genomic characteristics of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel, which comprises 80 inbred lines of medaka that were bred from a wild population from the city of Kiyosu, southern Japan. In this chapter I plot the inbreeding trajectory of the MIKK panel and analyse a number of genomic characteristics relevant to its utility for the genetic mapping of complex traits, including: the panel's evolutionary relationship with other previously-established inbred medaka strains; the degree of homozygosity in the inbred lines; the rate of linkage disequilibrium decay across the panel; and the genomic repeats and structural variation present in their genomes.

In Chapter 3, I use a custom behavioural assay to characterise and classify bold-shy behaviours in 5 previously-established inbred medaka strains. I describe the assay, assess its robustness against confounding factors, and apply a hidden markov model (HMM) to classify the fishes' behaviours across a spectrum of boldness-shyness based on the individuals' distance and angle of travel between pre-defined time intervals. I describe how the strains differ in their behaviours over the course of the assay (a "direct genetic effect") and how the behaviour of a single "reference" strain (iCab) differs in the presence of different strains (an "indirect genetic effect").

In Chapter 4, I describe the bioinformatic processes and genetic association models that I used to map the variants associated with variation in the period of somite development, based on an F2-cross between the southern Japanese iCab strain, and the northern Japanese Kaga strain.

In Chapter 5, I explain how I ran the custom behavioural assay described in Chapter 3 over the MIKK panel to identify lines that diverge in both their own bold-shy behaviours (the direct genetic effect) and the extent to which they transmit those behaviours onto their tank partners (the indirect genetic effect). I then describe how I used those divergent lines as the parental lines in a multi-way F2-cross to identify the genetic variants associated with both direct and indirect genetic effects.

Finally, in Chapter 6, I turn to humans to compare and rank all complex traits in the GWAS Catalog based on the extent to which their associated alleles vary across global populations, using the Fixation Index (FST) as a metric, and the 1000 Genomes dataset as a sample of global genetic variation. I set out the bioinformatic pipelines used to process the data, present the distributions of FST for trait-associated alleles across the genome, and use the Kolmogorov-Smirnov test to compare the distributions of FST across different traits.

Altogether, this thesis describes some of the genomic characteristics of both medaka fish and humans, and how those variations relate to differences in complex traits, with a particular focus on the genetic causes of adaptive behaviours and the transmission of those behaviours onto one's social companions.





Birney, Ewan


Medaka, Genomics, Genetics, Behaviour, Indirect genetic effects, Social genetic effects


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
EMBL International PhD Programme