Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood LeukemiaReportar como inadecuado




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Journal of Biomedicine and BiotechnologyVolume 2010 2010, Article ID 369534, 13 pages

Research Article

Sainte-Justine Hospital Research Center, University of Montreal, 3175 Chemin de la Côte-Sainte-Catherine, Room B-467, Montreal, QC, Canada H3T 1C5

Department of Pediatrics, Faculty of Medicine, University of Montreal, 3175 Chemin de la Côte-Sainte-Catherine, Room 7955, Montreal, QC, Canada H3T 1C5

Department of Social and Preventive Medicine, Faculty of Medicine, University of Montreal, P. O. Box 6128, Station Centre-Ville, Montreal, QC, Canada H3C 3J7

Received 31 August 2009; Revised 11 November 2009; Accepted 15 March 2010

Academic Editor: Wenjiang J. Fu

Copyright © 2010 Jasmine Healy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry MS required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry MA when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad-case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia ALL. We identified putative fetomaternal effects at loci CDKN2A rs36228834 𝑃 = . 0 1 7 and CDKN2B rs36229158 𝑃 = . 0 2 2 that modulate the risk of childhood ALL. These data further corroborate the importance of the mother-s genotype on the susceptibility to early-onset diseases.





Autor: Jasmine Healy, Mathieu Bourgey, Chantal Richer, Daniel Sinnett, and Marie-Helene Roy-Gagnon

Fuente: https://www.hindawi.com/



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