Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2010, Article ID 853612, 4 pages doi:10.1155/2010/853612 Editorial Gene-Gene Interaction in Maternal and Perinatal Research Janet S. Sinsheimer, 1, 2 Robert C. Elston, 3 and Wenjiang J. Fu 4 1 Departments of Biomathematics and Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA of Biostatistics, School of Public Health, UCLA, Los Angeles, CA 90095, USA 3 Division of Genetic and Molecular Epidemiology, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA 4 The Computational Genomics Lab, Department of Epidemiology, Michigan State University, East Lansing, MI 48824, USA 2 Department Correspondence should be addressed to Wenjiang J. Fu, fuw@msu.edu Received 23 April 2010; Accepted 27 April 2010 Copyright © 2010 Janet S. Sinsheimer 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. Recent genomic research increases our understanding of the causes of complex diseases and strengthens the evidence that many complex diseases, even those with late age of onset, are caused in part by genetically induced, adverse prenatal envi- ronments. This special issue of the Journal of Biomedicine and Biotechnology specifically examines the evidence that gene-gene interactions during early development influence human traits and diseases. Mothers largely determine the fetal environment; there- fore the maternal genotypes are expected to influence fetal development. Two types of gene-gene interactions are pos- sible during pregnancy, intragenerational interaction, and intergenerational interaction. Intragenerational effects con- cern gene-gene interactions within an individual’s genome to affect their own disease outcome. Intergenerational effects lead to conflicts between a mother and her fetus in some cases and, in other cases, they lead to beneficial environments that protect against disease. Intergenerational interactions can occur between genes in a child’s genome affecting the mother’s phenotype or between genes in a mother’s genome affecting the child’s phenotype. There can also be interactions between the maternal genes and fetal genes, such as maternal-fetal genotype incompatibility, that cause changes in the mother’s or the child’s phenotype. Maternal-fetal genotype (MFG) incompatibility is not just a theoretical possibility. The most well-known example of this form of gene-gene interaction is Rhesus factor D- induced hemolytic disease of the newborn [1], in which a Rhesus-negative mother develops antibodies to her Rhesus- positive fetus, leading to destruction of fetal red blood cells. Gene-gene interactions have also been studied as causes of pregnancy complications such as gestational hypertension and diabetes [2], but they have rarely been studied as risk factors beyond pregnancy complications. MFG incompatibility, in particular, has been reported to play an important role in the development of a number of disorders, including preeclampsia, preterm delivery, small- for-gestational-age neonates, and schizophrenia. Although genetic conflict has been postulated as playing a role in these disorders, rigorous modeling and quantitative analysis of these gene-gene interactions have only begun recently, as a result of biotechnological developments that have made it possible to conduct these investigations. Researchers conducting genome-wide association studies (GWAS) occasionally test for intragenerational gene-gene interactions, but they seldom test for maternal genetic influences on the phenotypes—and almost never test for intergenerational gene-gene interactions. There are several reasons for these omissions. First, testing for maternal genetic influences requires that both mothers and children be genotyped. Very often, the father’s genotype is also required by numerous analytical methods. This requirement increases the number of individuals who must be genotyped and also increases the number of tests conducted, which makes the study expensive. Second, it may even be impossible to obtain maternal genotypes if the disease has an adult onset. It is our contention that limiting gene discovery to single- gene analysis using unrelated individuals is a mistake. With much of the genetic architecture of complex traits left unex- plained, more investment into intergenerational gene-gene interactions is warranted. The evidence for multiple genetic influences during early development takes on a variety of forms and the eight articles chosen for the special issue reflect this variety.
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