Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer
Section snippets
Multispecies sequences and alignments
The 209-kb mouse BAC clone RPCI23-117O7 contains the entire Gdf6 gene and extensive flanking regions [4]. Using the previously established sequence of this BAC as a reference, we have generated (∼2.7 Mb) or obtained (∼1.5 Mb) sequences of the orthologous genomic regions from 13 additional vertebrates (Fig. 1a). A previous PipMaker analysis of the mammalian GDF6 sequences has been described [16]. To examine the degree of noncoding conservation in other vertebrates, we obtained sequences from
Discussion
Previous human and mouse sequence comparisons suggested the presence of numerous conserved noncoding regions within and flanking the GDF6 gene [4], [16]. These regions represent tantalizing candidates for serving as cis-acting regulatory elements that mediate the complex expression of GDF6 [8], [9]. Here, we report an extension of those studies that has involved the generation and comparison of the sequence of the genomic region encompassing GDF6 in multiple additional vertebrates. Two
BAC clones and sequences
The Gdf6-containing mouse BAC RPCI23-117O7 sequence (GenBank No. AC058786) served as the reference for comparative analyses and corresponds to UCSC Genome Browser coordinates chr4:9,641,000–9,850,732 (mm4/NCBI build 32, October 2003). Orthologous human and rat genomic sequences were retrieved from the respective genome-wide data sets [16], [42], [43]. Minimally overlapping GDF6-containing BACs from rat, chimpanzee, baboon, cow, pig, cat, dog, platypus, and zebrafish were identified [17] and
Acknowledgments
We thank numerous people associated with the NISC Comparative Sequencing Program, in particular Robert Blakesley, Gerry Bouffard, Jennifer McDowell, Baishali Maskeri, Nancy Hanson, the many dedicated mapping and sequencing technicians, and other staff. We also thank Laura Selenke and Lissett Ramirez for expert technical assistance and Karen Deal, Maureen Gannon, Anna Means, and Laura Wilding for generously sharing equipment and advice. We also thank Ronald Chandler for helpful discussions.
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