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The limits of fine-scale mapping

✍ Scribed by Lucian P. Smith; Mary K. Kuhner

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
365 KB
Volume
33
Category
Article
ISSN
0741-0395

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✦ Synopsis

Abstract

When 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 (4__N__μ) 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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