Epistasis

The prior knowledge used in candidate locus studies commonly identifies several candidate loci that are biochemically or physiologically interrelated. As a consequence, the candidate locus approach often suggests possible interactions among several candidate genes in producing the phenotype of interest. For example, we have already seen how the electrophoretic alleles at the ApoE locus are associated with phenotypic variation in total serum cholesterol levels (Chapter 8). The two major...

Markers of Intrapopulation Disequilibrium

Another critical aspect of a population's recent evolution for understanding and interpreting present-day associations between markers and phenotypes is its demographic history of founder and bottleneck events. Populations with a recent history of founder or bottleneck effects are particularly valuable in quantitative genetic studies for several reasons 1. Founder and bottleneck effects augment the magnitude and physical extent of likely linkage disequilibria, thereby creating strong...

Linkage Disequilibrium And Multilocus Associations

As shown in Chapter 2, both past history as well as recurrent evolutionary forces influence the genetic parameter of linkage disequilibrium, D. The creation of disequilibrium is influenced by historical factors such as the exact haplotype background upon which a new mutation originated or historical admixture between two previously genetically differentiated subpopulations (Chapter 2). Recurrent processes such as the system of mating and the amount of recombination then influence the decay of...

Some Implications Of Impact Of Evolutionary History Upon Disequilibrium

The impact of the past as measured by D0 upon the present in multilocus systems can be either a boon or a bane, depending upon the question being addressed. As a boon, multilocus studies inherently contain information about the past history of present-day genetic variation and its mutational origins. Parts of this history can often be inferred from multilocus (or multi-nucleotide-site) studies and hence give us a window into the past. For example, one important mutation in human genetics is the...

Sources Of Linkage Disequilibrium

Given that some initial linkage disequilibrium is necessary before recombination can act as an evolutionary force in a random-mating population, it is important to understand what factors can create an initial disequilibrium. Many factors can create linkage disequilibrium, including Note that this list of factors that can generate linkage disequilibrium corresponds to the very same factors that are assumed not to occur in the simple Hardy-Weinberg model (Table 2.1). All of these factors will be...

Genetic Drift And Disequilibrium

Just as drift causes changes in allele frequencies, it also changes multilocus gamete frequencies. Genetic drift tends to create linkage disequilibrium and associations between loci by chance alone. As we consider more and more loci simultaneously, we subdivide any finite gene pool into more and more gametic categories, thereby tending to make any one particular gamete type more rare. Sampling error is a strong force of evolutionary change for any gamete type that is rare in a gene pool, so in...

U1 Co

Statistical parsimony haplotype tree for ApoE gene incorporating additional resolutions based on haplotype frequencies and knowledge of mutational motifs. Only one ambiguity exists in this tree, the connection of haplotype 22 to the remainder of the tree has two possible alternatives, indicated by dashed lines. The nucleotide sites that have experienced multiple, independent mutational events to the same state are circled. The two alternative connections of haplotype 22 both result...