ZFIN ID: ZDB-PUB-030527-24
Genetics of human laterality disorders: insights from vertebrate model systems
Bisgrove, B.W., Morelli, S.H., and Yost, H.J.
Many internal organs in the vertebrate body are asymmetrically oriented along the left-right body axis. Organ asymmetry and some components of the molecular signaling pathways that direct left-right development are highly conserved among vertebrate species. While individuals with full reversal of organ left-right asymmetry (situs inversus totalis) are healthy, significant morbidity and mortality is associated with perturbations in laterality that result in discordant orientation of organ systems and complex congenital heart defects. In humans and other vertebrates, genetic alterations of left-right signaling pathways can result in a wide spectrum of laterality defects. In this review we categorized laterality defects in humans, mice and zebrafish into specific classes based on altered patterns of asymmetric gene expression, organ situs defects and midline phenotypes. We suggest that this classification system will provide a conceptual framework to help consolidate the disparate laterality phenotypes reported in humans and vertebrate model organisms in order to refine our understanding of the genetics of left-right development. This approach will help suggest candidate genes and genetic pathways that might be perturbed in human laterality disorders and improve diagnostic criteria. Expected online publication date for the Annual Review of Genomics and Human Genetics Volume 4 is August 30, 2003. Please see http://www.annualreviews.org/catalog/pub_dates.asp for revised estimates.