Horse breeding programs specializing in overo have particular challenges compared with programs for other white patterns such as tobiano. Not only is there the possibility of producing a solid dark foal without the overo pattern but there is also the risk of producing an all-white foal that dies of complications from intestinal tract abnormalities (aganglionosis). As far as we are aware, overo horses themselves have no specific health risks. While breeding evidence shows that some overos are heterozygous for a gene that is lethal in the homozygous condition, it has not been easy to identify which horses have the overo gene that is associated with the lethal condition (LWO).

Occasionally even solid-colored horses without obvious body spotting patterns have been reported to sire or produce lethal white foals. Clearly the spotting pattern classified as overo is phenotypically and genetically heterogeneous. Over the last thirty years, breeders have sought advice to recognize those overos at risk to produce lethal white foals, but up to now no reliable trait identification system has been found.

Fortunately, recent research has identified the gene that produces the overo lethal and a DNA-based diagnostic test is now available to identify breeding horses at risk to produce lethal white foals. Breeders can use the test not only to avoid producing lethal white foals but also to identify new pedigree sources of the overo gene that may be useful in their particular programs. The gene appears to be associated with those overos often characterized as "frame overos" in Paints and Thoroughbreds, but is also present in some tobiano/overos, in some solid-colored (breeding stock Paint) offspring from overo matings and in some tobianos and Quarter Horses without obvious evidence of the overo pattern. The gene has also been identified in an overo Miniature Horse.

Genetic studies based on the new DNA diagnostic test for the LWO gene confirm the proposal that the lethal white overo is due to an offspring having two copies of a gene that in single copy usually produces the attractive color pattern known as overo. Using the letter "O" to symbolize the DNA sequence of the lethal white overo gene and "N" for the sequence of the non-overo, then the lethal white foals can be symbolized as OO, their overo parents as NO and non-overos as NN. When two NO overos are bred together, then it is predicted that 25% of the offspring will be lethal white (OO). The living offspring will be either overo (NO) or solid ("breeding stock") (NN). By avoiding the breeding together of stallions and mares that have a single copy of the lethal white overo gene (NO), it is possible to produce foals with the overo pattern without the possibility of producing lethal whites. From breedings between a solid (NN) and an overo (NO), solid and overo foals are expected in approximately equal numbers. These possibilities are shown below in checkerboard diagrams familiar to students of Mendelian genetics:

Breedings between LWO overos (NO x NO):