Figure 6

Genomic comparison of YAC Y593 and BAC mBAC293d08. (A) The PAX6 gene is located centrally in Y593 [17]. The 3' end of Y593 is marked by exon 4 of the ELP4 gene. YAC Y593 has not been end-sequenced but is known to reside between the STS markers AFM324yh5 ~20 kb 5' and D11S4662 ~17 kb 3' to the YAC and is approximately 420 kb in length. The DRR (downstream regulatory region) is defined at the 5' end by the SIMO breakpoint and at the 3' end by ELP4 exon 4 [31]. Mouse BAC mBAC293d08 spans the region 12 kb 5' to exon 0 of Pax6 through to approximately 0.6 kb before ELP4 exon7 and is 160 kb in length [31]. It therefore lacks the genomic region between ELP4 exons 4 and 7 that comprise part of the DRR region in the human. (B) LAGAN/VISTA pairwise alignment of human and mouse genomic intervals spanning the region from SIMO to ELP4 exon 4 [41,42]. The 3' extent of mBAC293d08 is shown by the blue bar and of Y593 by the green bar. Regions shaded pink demark regions of >50% sequence identity over a window of 100 bp. In the 3' region common to Y593 and Y1123, but absent from mBAC293d08, rankVISTA analysis identifies five non-coding regions that are evolving more slowly than a modelled neutrally evolving base sequence (1: 199 bp p = 2.2e-03, 2: 466 bp p = 1.3e-07, 3: 223 bp p = 8.3e-04, 4: 509 bp p = 1.0e-12 and 5: 1564 bp p = 1.6e-42) [43]. These highly conserved regions could contain regulatory elements responsible for differences in expression between the transgenic reporter mice carrying mBAC293d08 and Y1123.