Natural selection works against inherited traits and disorders that would reduce the ability to survive, thrive, and reproduce. Artificial selection can reduce the frequency of disease-liability genes, be neutral to their propagation, or sometimes preferentially select for them. Selection must be appropriately applied in order to improve breed health.

Purebred dog and pedigree cat breeds evolved through selection for conformational, behavioral, and/or working standards. With extreme phenotypic selection, breeders have purposely selected for disease liability, such as the brachycephalic syndrome, excessive amounts of skin or skin folds, and overangulation.

Selection for traits has been linked to disease liability, such as hyperuricosuria (SLC2A9) in Dalmatians, craniofacial defect (unpublished, Lyons) in Burmese, dermoid sinus (FGF3, FGF4, FGF19 and ORAOV1 duplication) in Ridgebacks, and osteochondrodysplasia (unidentified) in Scottish Folds. In some cases, the preferred trait can be genetically separated from the disease liability. In other cases, they are pleiotropic expressions of the same genotype.

Other disease liability genes are not linked to selection, but they lay in the genetic background of breeds. Many of these are ancient mutations that preceded the separation of and are shared by many breeds. These include complex disorders, such as hip dysplasia, patella luxation, and diabetes mellitus (Types 1 & 2). Several ancestrally ancient mutations cause simple Mendelian disorders, such as progressive rod-cone degeneration (prcd), multifocal retinopathy (cmr1), and hyperuricosuria (SLC2A9). Without direct selection, these can increase in frequency through the popular sire effect or genetic drift.

Some recommendations to improve the genetic health of breeds concentrate on selection to increase heterozygosity or minor allele frequencies. These methods 1) do not select against disease-liability genes; 2) will not prevent the phenotypic expression of dispersed genes; and 3) may reverse the effects of positive selection through blind manipulation of minor alleles. Health-based selection should be specifically directed against deleterious traits and genes.