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Comments on Snoek, L. Basten et al. (2009) International Worm Meeting "Genome-wide evidence for genetic robustness of the alternative splicing machinery in C. elegans." (0)
Overview
Snoek, L. Basten, Li, Yang, Breitling, Rainer, Riksen, Joost A.G., Jansen, Ritsert, & Kammenga, Jan E. (2009). Genome-wide evidence for genetic robustness of the alternative splicing machinery in C. elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
Alternative splicing is considered a major mechanism for creating multicellular diversity from a limited repertoire of genes. Here, we studied genetic variation in alternative splicing patterns in a recombinant inbred population of C. elegans, using whole-genome tiling arrays. This experiment allowed us to detect heritable differences in gene expression with exquisite sensitivity and resolution. Nonetheless, we find only a relatively small number of examples of heritable variation in alternative splicing patterns. This is in striking contrast to earlier observations in humans, which showed much less genetic robustness. This observation points to a profound difference in the regulation of the alternative splicing machinery, which parallels the differences in cellular diversity and developmental flexibility in the two species. Nevertheless some striking examples were found of heritable variation in alternative splicing patterns. We detected 382 genes with substantial heritable variation for at least one exon of which the large majority of eQTLs lead to a consistent differential expression across all exons of the affected gene. Some cases show evidence for a necessary refinement of existing gene definitions, predominantly by expanding known exons. We will present genome-wide proof for earlier hypotheses that in C. elegans the alternative splicing machinery exhibits a general genetic robustness, and only a minor fraction of genes shows heritable variation in splicing forms and relative abundance. Furthermore we will show some of these genes showing heritable variation in alternative splicing.