cats. The fur patterns characteristic of tortoiseshell cats are found almost exclusively in females, because only they randomly inactivate one X chromosome in every somatic hair cell. Thus, presuming that hair color determining genes are X-linked, it makes sense that whether the maternal or paternal X chromosome is inactivated in a particular hair cell can result in differential fur color expression. Compounding on Lyon's discoveries, in 1962 Ernest Beutler used female fibroblast cell lineages grown in culture to demonstrate the heritability of lyonization or random X-inactivation. By analyzing the differential expression of two existing, viable alleles for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) gene, Beutler observed that the inactivation of the gene was heritable across passaged generations of the cells. This pattern of dosage compensation, caused by random X-inactivation, is regulated across development in female mammals, following concerted patterns throughout development; for example, at the beginning of most female mammal development, both X chromosomes are initially expressed, but gradually undergo epigenetic processes to eventually achieve random inactivation of one X. In germ cells, inactivated X chromosomes are then once again activated to ensure their expression in gametes produced by female mammals. Thus, dosage compensation in mammals is largely achieved through the silencing of one of two female X chromosomes via X-inactivation. This process involves histone tail modifications, DNA methylation patterns, and reorganization of large-scale chromatin structure encoded by the X-ist gene. In spite of these extensive modifications, not all genes along the X chromosome are subject to X-inactivation; active expression at some loci is required for homologous recombination with the pseudo-autosomal region (PAR) of the Y chromosome during meiosis. Additionally, 10-25% of human X chromosome genes, and 3-7% of mouse X chromosome genes outside of the PARs show weak expression from the inactive X chromosome. Random X-inactivation demands that the cell can determine if it contains more than one active X-chromosome before acting to silence any extraneous X-chromosome(s). This process is known as “counting”. The exact molecular mechanism of counting is still unknown, but a popular model posits that autosomes produce factors that repress X-inactivation, while X-chromosome products that promote X-inactivation. These two conflicting forces are balanced such that if there is more than one X-chromosome X-inactivation will occur, but if there is only one, the autosomal products will successfully prevent the process. Not all random X-inactivation is entirely random. Some alleles, generally mutations in the X-inactivation center on the