A linkage map of three anonymous human DNA fragments and SOD-1 on chromosome 21.

Using DNA polymorphisms adjacent to single-copy genomic fragments derived from human chromosome 21, we initiated the construction of a linkage map of human chromosome 21. The probes were genomic EcoRI fragments pW228C, pW236B, pW231C and a portion of the superoxide dismutase gene (SOD-1). DNA polymorphisms adjacent to each of the probes were used as markers in informative families to perform classical linkage analysis. No crossing-over was observed between the polymorphic sites adjacent to genomic fragments pW228C and pW236B in 31 chances for recombination. Therefore, these fragments are closely linked to one another (theta = 0.00, lod score = 6.91, 95% confidence limits = 0-10 cM) and can be treated as one 'locus' with four high-frequency markers. There is a high degree of non-random association of markers adjacent to each of these two probes which suggests that they are physically very close to one another in the genome. The pW228C - pW236B 'locus' was also linked to the SOD-1 gene (theta = 0.07, lod score = 4.33, 95% confidence limits = 1-20 cM). On the other hand, no evidence for linkage was found between the pW228C-pW236B 'locus' and the genomic fragment pW231C (theta = 0.5, lod score = 0.00). Based on the fact that pW231C maps to 21q22.3 and SOD-1 to 21q22.1, we suggest that the pW228C-pW236B 'locus' lies in the proximal long arm of chromosome 21. These data provide the outline of a linkage map for the long arm of chromosome 21, and indicate that the pW228C-pW236B 'locus' is a useful marker system to differentiate various chromosome 21s in a population.