NDLI: Multipoint Linkage-Disequilibrium–Mapping Approach Based on the Case-Parent Trio Design

Content Provider	PubMed Central
Author	Liang, Kung-yee Hsu, Fang-chi Beaty, Terri H. Barnes, Kathleen C.
Copyright Year	2001
Abstract	In the present study we propose a multipoint approach, for the mapping of genes, that is based on the case-parent trio design. We first derive an expression for the expected preferential–allele-transmission statistics for transmission, from either parent to an affected child, for an arbitrary location within a chromosomal region demarcated by several genetic markers. No assumption about genetic mechanism is needed in this derivation, beyond the assumption that no more than one disease gene lies in the region framed by the markers. When one builds on this representation, the way in which one may maximize the genetic information from multiple markers becomes obvious. This proposed method differs from the popular transmission/disequilibrium test (TDT) approach for fine mapping, in the following ways: First, in contrast with the TDT approach, all markers contribute information, regardless of whether the parents are heterozygous at any one marker, and incomplete trio data can be utilized in our approach. Second, rather than performing the TDT at each marker separately, we propose a single test statistic that follows a χ2 distribution with 1 df, under the null hypothesis of no linkage or linkage disequilibrium to the region. Third, in the presence of linkage evidence, we offer a means to estimate the location of the disease locus along with its sampling uncertainty. We illustrate the proposed method with data from a family study of asthma, conducted in Barbados.
Related Links	http://dx.doi.org/10.1086/319504
Ending Page	950
Page Count	14
Starting Page	937
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	4
Volume Number	68
Language	English
Publisher	The American Society of Human Genetics
Publisher Date	2001-04-01
Access Restriction	Open
Rights Holder	The American Society of Human Genetics
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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