Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs

Bibliographic Details
Main Author:	Papachristou, Charalampos
Language:	English
Published:	The Ohio State University / OhioLINK 2005
Subjects:	Linkage Analysis Confidence Intervals Confidence regions Putative Trait Genes Coverage Probability Confidence Level Genetic Markers SNPs Microsatellite
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=osu1124226056

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record_format	oai_dc
spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-osu11242260562021-08-03T05:50:17Z Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs Papachristou, Charalampos Linkage Analysis Confidence Intervals Confidence regions Putative Trait Genes Coverage Probability Confidence Level Genetic Markers SNPs Microsatellite <p>As more and more dense, yet cost-effective, genetic maps become increasingly available, the focus of linkage analysis is shifting from testing for linkage signals to sufficiently localizing putative disease loci before fine mapping begins. Currently, there exists only a limited number of methods that provide confidence regions for the locations of trait loci. Among them is the confidence set inference (CSI) procedure based on the mean IBD sharing statistic for data from affected sib-pair studies described by Lin (2002) that deduces such regions with known lower bound on their coverage. Although this method has many attractive features, including avoidance of multiplicity adjustment for the number of markers scanned, its formulation poses some restrictions that limit its usefulness on practical applications. First, it assumes that all markers are 100% polymorphic, so that the IBD state at each of them is inferred unequivocally, an assumption rarely met in reality. Second, when the genetic map available is sparse, it tends to produce intervals that overcover the trait locus. Finally, its application requires knowledge of the IBD sharing distribution at the trait locus by an affected sib-pair. These probabilities are estimated using population disease characteristics that can be obtained through epidemiological studies with reasonable accuracy. However, there is a number of issues that renders this method of estimating the IBD distribution impractical.</p> <p>We propose several extensions that address some of the limitations of the CSI approach. First, we extend it to accommodate markers with incomplete polymorphism, thereby increasing its practical value. Next, we modify it so that it tests each location on the genome for its possibility to be the trait locus. This way, we obtain regions with known exact coverage probability, rather than placing a lower bound on it. Finally, a two-step application of the CSI approach promises to avoid using population disease characteristics, circumventing the issues associated with them. Through extensive simulations, theoretical results, and applications to real data we demonstrate that the new CSI versions are indeed effective tools for localizing genes, with increased capability, when compared to currently employed approaches.</p> 2005-08-24 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1124226056 http://rave.ohiolink.edu/etdc/view?acc_num=osu1124226056 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Linkage Analysis Confidence Intervals Confidence regions Putative Trait Genes Coverage Probability Confidence Level Genetic Markers SNPs Microsatellite
spellingShingle	Linkage Analysis Confidence Intervals Confidence regions Putative Trait Genes Coverage Probability Confidence Level Genetic Markers SNPs Microsatellite Papachristou, Charalampos Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
author	Papachristou, Charalampos
author_facet	Papachristou, Charalampos
author_sort	Papachristou, Charalampos
title	Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
title_short	Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
title_full	Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
title_fullStr	Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
title_full_unstemmed	Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
title_sort	constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs
publisher	The Ohio State University / OhioLINK
publishDate	2005
url	http://rave.ohiolink.edu/etdc/view?acc_num=osu1124226056
work_keys_str_mv	AT papachristoucharalampos constructingconfidenceregionsforthelocationsofputativetraitlociusingdatafromaffectedsibpairdesigns
_version_	1719426330475364352

Constructing confidence regions for the locations of putative trait loci using data from affected sib-pair designs

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