Content area
Full Text
Abstract. We have identified a human homologue of the Drosophila mnb gene (MNBH) on chromosome 21, while another study mapped an EST clone (R38268) with similarity to minibrain to human chromosome 1. This report describes the mapping of MNBH to a single locus on human chromo
some 21q22.2 by FISH and Southern blotting. Comparison of the similarities between the two sequences and mnb demonstrates that MNBH on chromosome 21 is the true human homologue of Drosophila mnb.
The minibrain gene of Drosophila melanogaster (mnb) encodes a serine/threonine protein kinase with an essential role in postembryonic neurogenesis (Tejedor et al., 1995). Flies with mutations in mnb are characterized by a reduction in size of the central brain hemispheres due to a decrease in the production of neuronal progeny, caused by abnormal spacing of neuroblasts (Tejedor et al., 1995). We recently identified a human MNBH gene (Guimera et al., 1996), which because of its location on human chromosome 21 in the so called "Down Syndrome Critical Region" is likely to be implicated in Down syndrome (DS). At a gross morphological level, DS brains are smaller than normal and have a decreased number of neurons (Kemper et al., 1989). Using human MNBH cDNA as a probe on mouse brain sections, we showed that the murine counterpart (Mnbh) is expressed in regions of the mouse brain which correspond to the regions of the human brain affected in DS (Guimera et al., 1996). By analogy with its function and mutant phenotype in Drosophila and its expression pattern in mouse, MNBH is hypothesized to play a role in the mental retardation observed in DS.
Banfi et al. (1996) have identified several human ESTs that show similarity to Drosophila genes. One of these ESTs showed similarity to Drosophila mnb and was mapped to human chromosome 1. So the question arises, is there more than one human MNBH gene? Here we demonstrate that the human mnb homologue is a single copy gene located on chromosome 21 at 21q22.2 and that the level of similarity between the chromosome 1 sequence and mnb is focused in the serine/threonine kinase catalytic domain of mnb.
Materials and methods
Sequence similarity searches
Similarity searches were performed using the BLASTX program. The sequences compared were the WashU-Merck...