Figure 6

Examples of potential applications of TRACER. (A) Using TRACER to obtain information about the regulatory potential of a specific interval. Two loci (Ndst3 and Zfhx3) are given as an example, with photos of lacZ-stained embryos with insertions close or far from these genes. (B) Searching TRACER for insertions with specific expression patterns can identify genomic positions where an inserted transgene will display a predicted activity. Three insertions with different patterns of expression in the fronto-nasal process are shown as examples. Such specific patterns can subsequently be exploited to re-target other transgenes with expression in the predicted domains through different techniques. (C) Overlapping deletions (red bars) and duplications (blue bars) over 14q12 entered in the DECIPHER database (http://decipher.sanger.ac.uk/) are associated with similar clinical phenotypes. TRACER insertions in the orthologous interval show that it corresponds to a large regulatory landscape associated with forebrain (green) and facial (brown) expression domains in E11.5 (SB-202250e1 and SB-202250) and E12.5 (SB-177175emb7) mouse embryos. LacZ expression in the ear of embryo SB-177175emb7 (star) is due to the presence of an additional insertion, SBlacC [2]. Enhancer regions (ovals, color-coded depending on their pattern of activity as shown in the schematized embryo; data from VISTA enhancer browser [28]) present in the proximity may contribute to these activities. By local remobilisation and Cre-mediated recombineering, the mouse line SB-202250 may be used to produce mouse models of the human aneuploidies associated with this largely non-coding interval.