Gene copy number variations are associated with many disorders characterized by high phenotypic heterogeneity. Disease penetrance differs even in genetically identical twins. Can such heterogeneity arise, in part, from increased expression variability of one dose genes? While increased variability in the context of single cell gene expression is well recognized, our computational simulations in...

Mutations of the Shaker (Sh) locus of Drosophila reduce, eliminate, or otherwise alter a transient potassium current, IA, in muscle. Recent molecular studies indicate that the Sh locus produces several proteins by alternative splicing, but the relationships of the variety of Sh gene products to IA channels in the various excitable membranes still remain to be determined. In Drosophila, many enz...

The evolution of heterogametic sex chromosomes is often-but not always-accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently e...

An example of autosomal dosage compensation involving the expression of the alcohol dehydrogenase (Adh) locus is described. Flies trisomic for a quarter of the length of the left arm of chromosome two, including Adh, have diploid levels of enzyme activity and alcohol dehydrogenase messenger RNA. Subdivision of the compensating trisomic into smaller ones revealed a region that exerts an inverse ...

Two models, Z Dosage and Dominant W, have been proposed to explain sex determination in birds, in which males are characterized by the presence of two Z chromosomes, and females are hemizygous with a Z and a W chromosome. According to the Z Dosage model, high dosage of a Z-linked gene triggers male development, whereas the Dominant W model postulates that a still unknown W-linked gene triggers ...

Dosage compensation modifies the chromatin of X-linked genes to assure equivalent expression in sexes with unequal X chromosome dosage. In Drosophila dosage compensation is achieved by increasing expression from the male X chromosome. The ribonucleoprotein dosage compensation complex (DCC) binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of...

The levels of alcohol dehydrogenase (ADH) do not exhibit a structural gene-dosage effect in a one to four dosage series of the long arm of chromosome one (1L) (Birchler 1979). This phenomenon, termed dosage compensation, has been studied in more detail. Experiments are described in which individuals aneuploid for shorter segments were examined for the level of ADH in order to characterize the g...

Dosage compensation ensures similar levels of X-linked gene products in males (XY or XO) and females (XX), despite their different numbers of X chromosomes. In mammals, flies, and worms, dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in one sex resulting in a change in gene expression from the affected X chromosome(s). In mammals an...