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Transmission ratio distortion in families from the Framingham Heart Study

BACKGROUND: One implicit assumption in most linkage analysis is that live-born siblings unselected for a phenotype do not share alleles greater than the Mendelian expectation at any particular locus. However, since most families are recruited for genetic studies because of the presence of disease, t...

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Autores principales: Paterson, Andrew D, Sun, Lei, Liu, Xiao-Qing
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866484/
https://www.ncbi.nlm.nih.gov/pubmed/14975116
http://dx.doi.org/10.1186/1471-2156-4-S1-S48
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author Paterson, Andrew D
Sun, Lei
Liu, Xiao-Qing
author_facet Paterson, Andrew D
Sun, Lei
Liu, Xiao-Qing
author_sort Paterson, Andrew D
collection PubMed
description BACKGROUND: One implicit assumption in most linkage analysis is that live-born siblings unselected for a phenotype do not share alleles greater than the Mendelian expectation at any particular locus. However, since most families are recruited for genetic studies because of the presence of disease, there is little data available to confirm that this is the case. We hypothesized that loci that behave in a non-Mendelian fashion could be identified using genotype data from the Framingham Heart Study families. We tested the hypothesis that live-born sibs, either stratified by or irrespective of gender, demonstrate excess sharing of alleles on the autosomes, i.e., transmission ratio distortion. Multipoint linkage analysis of siblings either according to gender or not was performed using an allele-sharing method. Such observations may have implications for the mapping of loci for complex disease and quantitative traits in human pedigrees. RESULTS: No results that reached genome-wide significance were observed. However, four regions demonstrated excess sharing of alleles at p < 0.002 when sibships were stratified by gender-three of which were present in males. Of note, a female-specific locus co-localized with region that is linked to mean systolic blood pressure in the same families. In addition, three other regions demonstrated excess sharing of alleles in sibships irrespective of gender, including a region on chromosome 10p14-p15 (p = 7.5 × 10(-4)). CONCLUSION: Although no loci meeting genome-wide significance were detected to demonstrate transmission ratio distortion, loci with suggestive evidence for linkage were detected. These may have implications for the mapping of susceptibility loci for complex disease in human pedigrees.
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spelling pubmed-18664842007-05-11 Transmission ratio distortion in families from the Framingham Heart Study Paterson, Andrew D Sun, Lei Liu, Xiao-Qing BMC Genet Proceedings BACKGROUND: One implicit assumption in most linkage analysis is that live-born siblings unselected for a phenotype do not share alleles greater than the Mendelian expectation at any particular locus. However, since most families are recruited for genetic studies because of the presence of disease, there is little data available to confirm that this is the case. We hypothesized that loci that behave in a non-Mendelian fashion could be identified using genotype data from the Framingham Heart Study families. We tested the hypothesis that live-born sibs, either stratified by or irrespective of gender, demonstrate excess sharing of alleles on the autosomes, i.e., transmission ratio distortion. Multipoint linkage analysis of siblings either according to gender or not was performed using an allele-sharing method. Such observations may have implications for the mapping of loci for complex disease and quantitative traits in human pedigrees. RESULTS: No results that reached genome-wide significance were observed. However, four regions demonstrated excess sharing of alleles at p < 0.002 when sibships were stratified by gender-three of which were present in males. Of note, a female-specific locus co-localized with region that is linked to mean systolic blood pressure in the same families. In addition, three other regions demonstrated excess sharing of alleles in sibships irrespective of gender, including a region on chromosome 10p14-p15 (p = 7.5 × 10(-4)). CONCLUSION: Although no loci meeting genome-wide significance were detected to demonstrate transmission ratio distortion, loci with suggestive evidence for linkage were detected. These may have implications for the mapping of susceptibility loci for complex disease in human pedigrees. BioMed Central 2003-12-31 /pmc/articles/PMC1866484/ /pubmed/14975116 http://dx.doi.org/10.1186/1471-2156-4-S1-S48 Text en Copyright © 2003 Paterson et al; licensee BioMed Central Ltd http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Proceedings
Paterson, Andrew D
Sun, Lei
Liu, Xiao-Qing
Transmission ratio distortion in families from the Framingham Heart Study
title Transmission ratio distortion in families from the Framingham Heart Study
title_full Transmission ratio distortion in families from the Framingham Heart Study
title_fullStr Transmission ratio distortion in families from the Framingham Heart Study
title_full_unstemmed Transmission ratio distortion in families from the Framingham Heart Study
title_short Transmission ratio distortion in families from the Framingham Heart Study
title_sort transmission ratio distortion in families from the framingham heart study
topic Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866484/
https://www.ncbi.nlm.nih.gov/pubmed/14975116
http://dx.doi.org/10.1186/1471-2156-4-S1-S48
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