Relative order and location of DNA sequences on chromosome 21 linked to familial Alzheimer disease

Recently, a gene causing familial Alzheimer disease (FAD) was linked to DNA probes on chromosome 21 by genetic analysis. To investigate the precise physical location of these DNA probes, we have constructed a physical map of this region of chromosome 21 by using quantitative Southern blot analysis of cell lines aneuploid for parts of chromosome 21. The following DNA sequences were investigated: D21S16, D21S13, FB68L (cDNA probe for the amyloid protein precursor [APP] gene), and D21S1. We find that all DNA probes are located in the same region of chromosome 21, in q11.2-q21.05. We further show that D21S16 must be centromeric to D21S13, because D21S16, but not D21S13 is present in one copy in a cell line with deletion of the region 21pter-21q 11.2. High resolution chromosome analysis is presented to define this breakpoint. This new panel of aneuploid cell lines will allow the rapid mapping of new DNA probes in the vicinity of the FAD gene.