ABSTRACT
Might Contribute to Autism ...................................................................... 334 17.6.1 Oxidative Stress .......................................................................... 335 17.6.2 Synaptic Pruning and the MHC ................................................. 336 17.6.3 HLA-DR4 and High Relative Birthweight ................................. 337 17.6.4 Maternal Antibodies and Autism ............................................... 337 17.7 Future Studies of HLA-DR4 in Autism ..................................................... 337 References .............................................................................................................. 337
TABLE 17.1 Reports of Teratogenic Alleles
Neurodevelopmental disorders are complex disorders in which multiple genes contribute to the clinical phenotype and their effect is modi ed by environmental factors. Genes contributing to neurodevelopmental disorders are usually thought of as acting in the affected individual, i.e., the child or adult with the neurodevelopmental disorder. In the gene-teratogen model, an additional class of genes is considered, maternal genes that act in the mother to contribute to the phenotype of their affected offspring. The alleles of maternal genes that act in this way are termed “teratogenic alleles” because their effect is in some ways similar to ingested maternal teratogens that affect fetal development. Teratogenic alleles most likely act in the mother during pregnancy to modify the development of the embryo or fetus, e.g., brain development in the affected children, although action on the ovum or in the ovum before conception is also possible. These maternal genes may interact with fetal genes and with environmental factors. These fetal genes are termed “modifying or speci city alleles” in the gene-teratogen model since they may modify the severity of the phenotype in the fetus or determine which organ is affected. At present, at least 34 reports of teratogenic alleles have been published (Johnson et al., 2008, Table 17.1; Johnson et al., 2009).
