Conclusions
Analysis of the presence or absence of a gene in the ABC transporter superfamily across vertebrates demonstrates a tremendous diversity in potential efflux functions. Nearly all the ABC genes have been disrupted in the mouse, and most display a phenotype, often including lipid and cholesterol transport, blood chemistry, developmental or neurological abnormalities, or lethality. Several polymorphisms in or near human ABC genes are genome-wide associated with either known important human traits or new phenotypes. For example, there is an association of polymorphisms in the ABCA5 gene cluster with HDL- and LDL-cholesterol levels providing strong evidence that one or more genes in this locus are essential for cholesterol homeostasis. Somatic mutations in ABC transporters do not seem to be a significant mechanism of carcinogenesis; however, several genes are amplified or overexpressed in specific tumor types, suggesting future research areas. Finally, several ABC genes have deficient levels of loss-of-function mutation and are likely to be essential genes. In contrast, at least three genes (CFTR , ABCG2 , and ABCG8 ) have an apparent excess of non-synonymous or loss-of-function mutations. Future genomic, genetic, and functional studies of these transporters across vertebrate species will likely yield important new insights into biology and disease.