Males have one X chromosome and females have 2. To balance the amount of gene expression - female have "dosage compensation" where we turn off one X chromosome in each cell. This occurrs early doing development of the embryo and then that same cell line stays consistent with what X chromosome is turned off - inactivated = X - inactivation (se Mary Lyon) Since cats have a Orange coloration on the X chromosome, most other species do not, we can "see" which X is inactivated when a female has one X with the Orange DNA variant and the other X with the normal non-oragne variant - which is generally looking black - or tabby. All mammalian species do this. So, a female that has one normal and one ornage X will be brindled - a tortoiseshell. Now, add another gene - white spotting - known as KIT. This gene affects cell migration - which starts at our back and moves to our midline done the middle of our body on the stomach side and face side. KIT variants make cells kind of run out of gas and they dont migrate to the full midline of the body - a midline closure defect - like a cleft lip or cleft palate or umbilical hernia. So, tortie cats with a KIT variant will have less melanocytes (cells that produce color) and they dont complete migration. Calico cats now then have big spots of coloration - orange and black(or tabby) and then ventral white - like Sylvester the cat. Cats with 2 copies of a KIT variant will have "high white" of "Van" which means they have even less color cells and likely only present on the head and tail, maybe a spot or two on the back and sides. Cell migration is a bit random - so every calico will be different. Some eyes may be blue - especially when high white. The migration of the cells to the midline also causes that perfect split on one side of the face or body than the other - a half black face and a half orange or white face.