Descriptive analysis and inference of Higher-order Linkage Disequilibrium

Genetic studies in human populations have unveiled a vast number of polymorphisms. This variability is shaped by evolutionary forces such as drift, selection, bottlenecks and more. The approach applied in this thesis is based on haplotype method meaning that we consider block of SNPs of the human genome. This method has an advantage over single SNP analysis. The aim of the thesis is to characterise the genetic history based on the correlation structure of polymorphisms. This correlation structure is characterised in terms of joint cumulants which generalise linkage disequilibrium (LD) to more than two loci. The advantage of a multilocus LD (high order LD) measurement over a pairwise LD measurement is that the latter is not adequate to detect simultaneous allele associations among multiple markers. Characteristic patterns of this standardised higher-order LD are summarised in a catalogue for all possible genetic histories in an exponentially growing population. Heatmap approach was...Show moreGenetic studies in human populations have unveiled a vast number of polymorphisms. This variability is shaped by evolutionary forces such as drift, selection, bottlenecks and more. The approach applied in this thesis is based on haplotype method meaning that we consider block of SNPs of the human genome. This method has an advantage over single SNP analysis. The aim of the thesis is to characterise the genetic history based on the correlation structure of polymorphisms. This correlation structure is characterised in terms of joint cumulants which generalise linkage disequilibrium (LD) to more than two loci. The advantage of a multilocus LD (high order LD) measurement over a pairwise LD measurement is that the latter is not adequate to detect simultaneous allele associations among multiple markers. Characteristic patterns of this standardised higher-order LD are summarised in a catalogue for all possible genetic histories in an exponentially growing population. Heatmap approach was applied to visualise and interpret the behaviour of the LD patterns under different population scenarios. Tests were developed to determine whether given data is more likely to stem from a particular catalogue entry than others. These tests were developed using Monte Carlo techniques. Simulations were complemented by an analysis of part of the public HapMap project.Show less

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Descriptive analysis and inference of Higher-order Linkage Disequilibrium