Charles M. Woolf

Does the genotype for schizophrenia often remain unexpressed because of canalization and stochastic events during development

BACKGROUND It has been well established in the literature that a strong genetic component exists for schizophrenia. Available data are compatible with the hypothesis that for most cases of schizophrenia, the genetic component consists of multiple genes acting in an additive manner with the genotype for schizophrenia being present when the number of genes is greater than a threshold number. Twin studies suggest that the genotype for schizophrenia is unexpressed in some individuals who carry it. This phenomenon of reduced penetrance has led to a diversity of hypotheses concerning the aetiology of schizophrenia. Based on a review of the literature a neurodevelopmental model is proposed for schizophrenia that involves the actions of the schizophrenia genotype, canalization and stochastic events. CONCLUSIONS The schizophrenia genotype is programmed to disrupt the migration of neuronal cells in the developing cortex during the second trimester, resulting in impaired embryogenesis. The presence of a specific lesion is the reason for the onset of schizophrenia later in life. The genotype for schizophrenia often remains unexpressed, or demonstrates variable expressivity, because of the actions of canalization and stochastic events that may allow migrating neuronal cells to reach or approach the target data. Stochastic events also influence whether canalization will be successful, therefore, chance plays a major role under normal conditions in determining whether the schizophrenia genotype will be expressed. Certain environmental factors acting during early development, such as high temperature resulting from maternal illness, may increase the penetrance of the schizophrenia genotype.

Does homozygosity contribute to the asymmetry of common white leg markings in the Arabian horse

Common white and facial markings have a multifactorial mode of inheritance inEquus caballus and result from the absence of melanocytes in the unpigmented areas. Directional asymmetry and fluctuating asymmetry apparently account for the total asymmetry of common white leg markings. Using computerized records obtained from the Arabian Horse Registry of America, Inc., and the International Arabian Horse Association, studies were carried out to determine if homozygosity increases the total asymmetry in common white leg markings by presumably promoting fluctuating asymmetry. The results were as follows: (1) Arabian horses that are symmetrical and asymmetrical for common white leg markings have similar distributions of inbreeding coefficients; (2) Arabian and half-Arabian horses have similar concordance values, in general, for specific white markings in both their forelegs and hind legs. It is concluded that homozygosity does not contribute to the total asymmetry of common white leg markings in the Arabian horse.

Genetic variability of the tumorous-head maternal effect in Drosophila melanogaster

SummaryThe tumorous-head maternal effect in Drosophila melanogaster is produced by a recessive gene (tuh-1) in chromosome 1. Polymorphism exists at this locus. This maternal effect, which is part of the normal variation found in this species, is detected with the aid of a mutant gene. In the presence of the maternal effect, a semi-dominant mutant gene (tuh-3) causes homoeotic changes in the eye-antennal imaginal discs. The phenotype in the adult is known as the tumorous-head abnormality. The mutant gene, which is located in the right arm of chromosome 3, is characterized by reduced penetrance. Using the penetrance of the mutant gene as the criterion, the results of these experiments show that the level of the maternal effect activity is influenced remarkably by modifiers present in wild type strains. The assay is to mate females homozygous for tuh-1 with males homozygous for tuh-3 and to determine the percent of the offspring showing the tumorous head abnormality. Using this procedure, it was observed that parental females with various combinations of chromosomes 1 and 3 from Lausanne and Stephenville wild type strains show great variability in the level of maternal effect activity. Modifiers in chromosome 1 and 3 from the Stephenville strain increase the level of the maternal effect activity. The level is reduced if these chromosomes are replaced by those from the Lausanne strain. A major locus in chromosome 3 is in the same region occupied by clusters of functionally related genes with regulating action. These results demonstrate that the penetrance of a mutant gene, which acts during embryogenesis, is influenced by modifiers which act during oogenesis.

Positive and negative geotaxis: Sex-linked traits inDrosophila pseudoobscura

Using a Hirsch classification maze, selection was made for positive and negative geotactic behaviors in three different strains ofDrosophila pseudoobscura. Hybridization studies were then carried out with flies from the diverged strains. The geotactic scores of the parents and F1 flies indicate that both negative and positive geotactic behaviors in these strains are strongly influenced by genes in the X chromosome. Additional hybridization studies using flies from strains with similar phenotypes suggest that the diverged strains contain similar alleles and the number of loci in the X chromosomes responsible for these types of behavior is limited. The loci may be highly organized in the X chromosome.

Directional and anteroposterior asymmetry of common white markings in the legs of the Arabian horse: response to selection

Arabian bay horses manifest, on the average, more common white markings in their hind legs than their forelegs (anteroposterior asymmetry) and more common white markings in their left legs than their right legs (directional asymmetry). To determine if genetic variation exists for these types of asymmetry, the phenotypic response was studied in bay foals when their dams and sires were selected for the directions of fore-hind and left-right differences. In the fore-hind studies, the quantitative shifts in the bay foals were in the direction specified by the selection scheme and the observed deviations were all statistically significant. The shifts were also consistently in the direction favored by selection in the left-right studies, but only two of six observed deviations were statistically significant using a one-tailed test of significance. Thus, only marginal statistical evidence is available to support the observed consistent responses to selection in the left-right studies. These differential responses are reflected in the magnitudes of the heritability estimates. Based on the overall results, it is concluded that both types of asymmetry have a genetic basis in the Arabian horse, but much more genetic variation is present for anteroposterior asymmetry than for directional asymmetry.