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About the Authors:
Leila Taher
Affiliation: Computational Biology Branch, National Center for Biotechnology Information, Bethesda, Maryland, United States of America
Nicole M. Collette
Affiliation: Biology and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, United States of America
Deepa Murugesh
Affiliation: Biology and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, United States of America
Evan Maxwell
Affiliation: Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America
Ivan Ovcharenko
Affiliation: Computational Biology Branch, National Center for Biotechnology Information, Bethesda, Maryland, United States of America
Gabriela G. Loots
* E-mail: [email protected]
Affiliations Biology and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, United States of America, School of Natural Sciences, University of California Merced, Merced, California, United States of America
Introduction
The developing limb serves as an ideal model for studying differentiation of pluripotent mesenchymal cells into several distinct tissues, including cartilage, muscle, blood vessels, tendons and endochondral bone [1]. While the limb is a well established model system for studying genetic factors that regulate tissue patterning, differentiation and growth, the last decade of limb development research has been dominated by the same collection of widely studied genes, with little introduction of new candidate contributors. However, malformations affecting the limbs, more specifically the number of digits with which an infant is born, are among the most frequent congenital defects recorded in humans, occurring as often as 1 in 1000 live births. Currently, there are about 221 syndromes described with polydactyly and 120 syndromes with oligodactyly [2]. Despite this wide prevalence of limb abnormalities, to date only ∼84 genes have been associated with syndromes that include limb defects, 15 of which have described polydactyly [2]. Similarly, the sequential and tightly interconnected cellular events that lead to the establishment of each individual tissue type, as well as the three-dimensional molecular interplay within the vertebrate limb are not yet fully understood [3]. Finally, we have yet to grasp how the genome specifies fore- and hind-limb patterning to establish limb identity and ultimately result in the formation of complex homologous structures that are distinct in shape and function, such as the human hand and foot [4], [5].
The availability of DNA microarray technologies has provided the opportunity to comprehensively examine gene expression in serially homologous structures, such as the...