Comparative transcription map of the wobbler critical region on mouse chromosome 11 and the homologous region on human chromosome 2p13-14

The gene content of the investigated regions was highly conserved between the two species: 20 orthologous genes were identified on our BAC/YAC contig comprising 4.5 Mb between REL/Rel and RAB1A/Rab1a. Exceptions were pseudogenes ELP and PX19 whose mouse counterparts were not located within the analyzed region. Two independently isolated genomic clones indicate an inversion between man and mouse with the inverted segment being identical to the wobbler critical interval. We investigated the wobbler critical region by extensive STS/EST mapping and genomic sequencing. Additionally, the full-length cDNA sequences of four newly mapped genes as well as the previously mapped gene Otx1 were established and subjected to mutation analysis. Our data indicate that all genes in the wr critical region have been identified.Unexpectedly, neither mutation analysis of cDNAs nor levels of mRNAs indicated which of the candidate genes might be affected by the wr mutation. The possibility arises that there might be hitherto unknown effects of mutations, in addition to structural changes of the mRNA or regulatory abnormalities.The conservation of genomic structure between two or more species is the basis of comparative genomics. During the process of evolution the distribution of genes on chromosomes is rearranged by illegitimate recombination and translocation. Species sharing a recent common ancestor tend to have fewer chromosomal rearrangements than distantly related species [1]. Orthologous genes serve as landmarks for the definition of related chromosomal regions. Orthologous segments are defined by at least one pair of orthologous genes; conserved synteny relates to at least two pairs of orthologous genes located on the same chromosomal segment in two different species [2].With increasing sequence data comparative genomics is no longer restricted to genes, as evolutionary conserved intergenic sequences [3] can now also be taken into account. In addition, comparison of genomic sequenc