12.18: Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes, which are involved in pigmentation and also in the early development of the ear. SOX10 is also expressed in nerve tissue that eventually contributes to the enteric nervous system in the gut, which controls the contractions necessary for waste elimination. In this way, SOX10 exhibits pleiotropic effects, because it influences multiple phenotypes.
Pleiotropic Effects of SOX10
Pleiotropy can arise through several mechanisms. Gene pleiotropy occurs when a gene has various functions due to encoding a product that interacts with multiple proteins or catalyzes multiple reactions. For example, in humans, an abnormal copy of the SOX10 gene, in which a region is deleted, can lead to developmental defects that include a white forelock, different-colored irises (e.g., one blue and one brown), and regions of unpigmented skin. These traits are all symptoms of a disorder called Waardenburg Syndrome Type 4, or WS4, an autosomal recessive disorder that results in multiple pigment defects. The pleiotropic effects of SOX10 in WS4 extend toward additional symptoms seemingly unrelated to pigmentation, such as hearing loss. Individuals with WS4 also suffer from a lack of intestinal contractions, resulting in an enlarged colon and difficulties eliminating waste. These symptoms indicate that, in addition to affecting pigmentation, SOX10 also impacts hearing and contributes to an abnormal bowel phenotype.
Early Development Expression Patterns
The ability of SOX10 to exert its pleiotropic effects may be explained by its expression in early embryonic and fetal development, during which it is found in neural crest cells that eventually lead to the formation of pigment cells called melanocytes. In addition to pigmentation, melanocytes influence hearing, as they are found in the developing ear. SOX10 is also expressed in ganglion cells of the terminal hindgut that contribute to the formation of the gastrointestinal tract and control intestinal contractions. This explains the elimination problems and enlarged colons in some WS4 individuals. Therefore, SOX10 is an example of a pleiotropic gene, because it has an impact on several developmental processes and influences multiple phenotypic traits.
