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.