TY - JOUR
T1 - Multipoint linkage-disequilibrium - Mapping approach based on the case-parent trio design
AU - Liang, Kung Yee
AU - Hsu, Fang Chi
AU - Beaty, Terri H.
AU - Barnes, Kathleen C.
N1 - Funding Information:
This work is supported, in part, by National Institutes of Health grant GM49909. We thank the following individuals for their contribution to the Barbados study: Raana P. Naidu, Paul N. Levett, Renate Nickel, Linda Freidhoff, Maria Stockton, Rasika Mathias, and Xielun Xue. We wish to thank the families in Barbados for their generous participation in this study. We also thank the staff of the Leptospira Laboratory, Barbados, for their technical support, and the Ministry of Health, Barbados, for permission to conduct this study in Barbados. Finally, we acknowledge the helpful comments, from the two reviewers and from Dr. M. Danielle Fallin, which improved the quality of this work.
PY - 2001
Y1 - 2001
N2 - 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 x2 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.
AB - 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 x2 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.
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U2 - 10.1086/319504
DO - 10.1086/319504
M3 - Article
C2 - 11254451
AN - SCOPUS:0035075317
SN - 0002-9297
VL - 68
SP - 937
EP - 950
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -