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Example 1 (continued)

These results indicate that the loss of most of the critical locus control region accounts for the low beta-globin production in the patient carrying the Hispanic deletion. Indeed, mapping (Driscoll et al., 1989) and analyzing (Forrester et al., 1990) this deletion were major contributions to our understanding of the locus control region (Grosveld et al., 1987; Tuan et al., 1989).

In more detail, many aspects of the information presented here fit with known features of gene regulatory elements. The regulatory region HS2 is the major contributor to the enhancement function of the locus control region. It is marked specifically by the DNase HS (red tracks) and FAIRE (lower green tracks) data, and it is found in a broad region of hyperacetylated histones in chromatin (black track). It is highly conserved (Siepel et al., 2005), along with many other segments in the locus control region. The regulatory potential track captures not only conservation but also pattern and content information from sequence alignments, based on discrimination in training sets (Kolbe et al., 2004); it brings out the HSs in the locus control region very cleanly.

The region around HS3 shows more complexity, with multiple signals in conservation and regulatory potential. Mutagenesis and experimental tests support roles for all of these subregions (Molete et al., 2001, 2002).

Closer comparison of these tracks provides additional insights and suggests more experiments. Thus, while PhenCode can be helpful to clinicians for diagnostics, it also serves biomedical researchers by integrating multiple types of information and facilitating the generation of testable hypotheses to improve mankind's understanding of both the functions of genomic DNA and the mechanisms by which it achieves those functions.

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