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Genetic Epidemiology
Article . 2008 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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The limits of fine‐scale mapping

Authors: Lucian P, Smith; Mary K, Kuhner;

The limits of fine‐scale mapping

Abstract

AbstractWhen a novel genetic trait arises in a population, it introduces a signal in the haplotype distribution of that population. Through recombination that signal's history becomes differentiated from the DNA distant to it, but remains similar to the DNA close by. Fine‐scale mapping techniques rely on this differentiation to pinpoint trait loci. In this study, we analyzed the differentiation itself to better understand how much information is available to these techniques. Simulated alleles on known recombinant coalescent trees show the upper limit for fine‐scale mapping. Varying characteristics of the population being studied increase or decrease this limit. The initial uncertainty in map position has the most direct influence on the final precision of the estimate, with wider initial areas resulting in wider final estimates, though the increase is sigmoidal rather than linear. The Θ of the trait (4Nμ) is also important, with lower values for Θ resulting in greater precision of trait placement up to a point—the increase is sigmoidal as Θ decreases. Collecting data from more individuals can increase precision, though only logarithmically with the total number of individuals, so that each added individual contributes less to the final precision. However, a case/control analysis has the potential to greatly increase the effective number of individuals, as the bulk of the information lies in the differential between affected and unaffected genotypes. If haplotypes are unknown due to incomplete penetrance, much information is lost, with more information lost the less indicative phenotype is of the underlying genotype. Genet. Epidemiol. 2009. © 2008 Wiley‐Liss, Inc.

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Keywords

Population Density, Recombination, Genetic, Likelihood Functions, Models, Genetic, Quantitative Trait Loci, Chromosome Mapping, Penetrance, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Genetics, Population, Sample Size, Mutation, Humans, Epidemiologic Methods, Software

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Average
Average
Average
bronze