Systematic analysis of genes localized in Xq28

A. Kolb, H.Bausbacher

Selected regions of the human genome were analysed systematically to identify genes causing monogenic diseases at differing genomic locations. For this approach several new technologies were developed within the department. Based on the establishment of genetic maps of the subchromosomal region Xq28 in recent years, various candidate genes for genetic disorders were isolated. One of these, the DKC1 gene, which is responsible for causing the X-linked recessive dyskeratosis congenita, is further analysed. Also, a mutation in the MECP2 gene was found to be the cause of one rare form of mental retardation (Klauck et al., 2002).The systematic generation of physical and transcription maps allowed the identification of most genes localized in this region, supporting the hunt for new disease genes (Copley et al., 2002), and making Xq28 one of the best characterized regions of the human genome (Aradhya et al., 2002, McPherson et al., 2001, Nadeau et al., 2001).

The analysis of the subchromosomal region Xq28 serves as a model system for analysis of the whole human genome. The importance of this region arises from the high gene density and the large number of genetic disorders linked to this 10 Mb region. Although most of these genes have been identified and sequenced, the extent of characterization at the level of expression and function varies, making correlations between the genotype and the phenotype of genetic disorders almost impossible. Systematic functional analysis of all genes that localise to this special region is being carried out using RNA in situ hybridization to investigate the developmental and tissue-specific expression of orthologous genes in the mouse (Kolb, et al, 2006). Furthermore the subcellular localization of the corresponding proteins is examined.