Genomic resources have been developed and used successfully over the past decade to help define the genetic basis for traits in traditional model systems. These resources, however, have not been applied widely to the study of traits in natural populations. Many emerging model systems, including the cavefish Astyanax mexicanus, are especially favorable organisms for the study of numerous poorly-understood developmental processes. Specifically, adaptation to the cave microenviroment in the past 10,000 years has resulted in the accumulation of a variety of degenerate traits, e.g., complete loss of eyes and pigmentation. The persistence of a surface river-dwelling, intraspecific member of this genus has allowed these fish to be interbred to create hybrids. The Tabin lab has developed a recombination-based linkage map using hundreds of microsatellite markers to facilitate quantitative trait locus (QTL) studies. Since cavefish are close phylogenetic relatives of the well-studied fish, Danio rerio, they share a remarkable level of genomic synteny. The geological and natural history of these fish are well-rooted in a sizeable classical and contemporary literature. In addition, several populations of cavefish residing in multiple caves within the Sierra de El Abra region of central Mexico, allow for analyses of parallel evolution and the convergence of phenotypic traits in different populations of Astyanax having evolved from geologically-isolated cave populations. Finally, cavefish are robust organisms that are easily maintained and bred in the Tabin laboratory. To better understand the genetic basis for degenerate morphologies in Astyanax, a three-fold strategy is proposed. First, a genome-wide linkage map, previously constructed and published by the Tabin laboratory, comprised of hundreds of microsatellite markers will be analyzed for their syntenic positions in the closest relative of Astyanax with a sequenced genome, the zebrafish Danio rerio. This work will be aimed at anchoring the cavefish linkage map to the zebrafish physical map. Second, utilizing QTL analyses, I will identify the location of candidate genes associated with the development of four traits: visual system degeneration, loss of melanin-producing cells, variability in rib number and morphology, and facial bone dysgenesis. Third, genes closely linked to the QTL described above will be subjected to functional assays to understand and characterize their potential role(s) in the loss of these characteristics. Several of the degenerative traits present in the cave-form of Astyanax may have equivalent or parallel bases in human degenerative disorders. Thus, results obtained in the QTLs proposed in this study may also have implications for better characterizing genetic events leading to analogous human clinical diseases ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F08-G (20))
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Portnoy, Matthew
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Harvard University
Schools of Medicine
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Gross, Joshua B; Borowsky, Richard; Tabin, Clifford J (2009) A novel role for Mc1r in the parallel evolution of depigmentation in independent populations of the cavefish Astyanax mexicanus. PLoS Genet 5:e1000326
Gross, Joshua B; Protas, Meredith; Conrad, Melissa et al. (2008) Synteny and candidate gene prediction using an anchored linkage map of Astyanax mexicanus. Proc Natl Acad Sci U S A 105:20106-11