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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major discoveries in modern genetics is the phenomenon of genomic, or parental, imprinting. The parent-of-origin effects seen after transmission of an imprinted gene from parents to their children do not follow the genetic rules postulated by Gregor Mendel. This has obvious consequences for genetic counselling. Aberrant imprinting can lead to a wide variety of clinical disorders ranging from the development of tumours to pronounced growth abnormalities and from mental retardation to developmental disorders of language or autism as seen in Turner's syndrome. Here we describe the basic principles of genomic imprinting and discuss a number of well-characterized clinical disorders associated with genomic imprinting.
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PMID:Genomic imprinting: concept and clinical consequences. 1021 10

Schizophrenia, autism and depression do not inherit by Mendel's law, and the search for a genetic basis seems unsuccessful. Schizophrenia and autism relate to low birth weight and pregnancy complications, which are associated with developmental adaptations by "programming". Epigenetics might constitute the basis of programming and depend on folate status and one-carbon metabolism in general. Early folate status of patients with schizophrenia might be compromised as suggested by (i) coinciding incidences of schizophrenia and neural tube defects (NTDs) in the Dutch hunger winter, (ii) coinciding seasonal fluctuations in birth of patients with schizophrenia and NTDs, (iii) higher schizophrenia incidence in immigrants and (iv) higher incidence in methylene tetrahydrofolate reductase 677C-->T homozygotes. Recent studies in schizophrenia and autism point at epigenetic silencing of critical genes or chromosomal loci. The long-chain polyunsaturated fatty acids (LCPUFA), arachidonic acid (AA, from meat) and docosahexaenoic acid (fish) are components of brain phospholipids and modulators of signal transduction and gene expression. Patients with schizophrenia and, possibly, autism exhibit abnormal phospholipid metabolism that might cause local AA depletion and impaired eicosanoid-mediated signal transduction. National fish intakes relate inversely with major and postpartum depressions. Five out of six randomized controlled trials with eicosapentaenoic acid (fish) have shown positive effects in schizophrenia, and 4 of 6 were favorable in depression and bipolar disorders. We conclude that folate and LCPUFA might be important in both the etiology and severity of at least some psychiatric diseases.
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PMID:Folate and long-chain polyunsaturated fatty acids in psychiatric disease. 1665 Jul 50

More than a century ago, Wilhelm Johannsen proposed the terms "genotype" and "phenotype" to study heredity. Much of what we know about genetics and behavior has evolved since then, especially how causality from genotypes can be inferred from observational studies of phenotypes. Unfortunately, there are genotypes that produce complex clinical-behavioral phenotypes-pleiotropy. In addition, there are often many genotypes that produce the same phenotype, adding a layer of complexity in establishing valid genotype-phenotype relationships. Unlike the relative simplicity of some phenotypes, behavioral phenotypes, especially those characteristics considered aberrant, are multidimensional and often not easily defined operationally. An alternate approach which attempts to identify less evident manifestations below the level of the phenotype but along the pathway to the prospective genotype-endophenotypes-could prove useful in detecting genes that generate these markers. However, operational definitions of intermediate phenotypes vary, less overt neurobiological expressions for some disorders-autism-have not been found, and studies of endophenotypes associated with schizophrenia have been not been very successful. Another approach, suggested by Sewall Wright, uses path analysis to identify causal variables that produce phenotypes. Innovative models of causality have been developed recently by genetic epidemiologists that incorporate Mendel's second law, and Mendelian randomization has been successful in identifying genotypes associated with some diseases, for example, diabetes and cancer. Regrettably, shortcomings regarding genetic markers associated with intermediate phenotypes have been found, although there are statistical procedures to remedy matters. As in any science, genetic researchers need to consider carefully the models of causality they choose.
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PMID:Whither the genotype-phenotype relationship? An historical and methodological appraisal. 2883 62