A sequence-based integrated map of chromosome 22

The near-completion of the sequence for chromosome 22q revolutionizes map integration. We describe a sequence-based integrated map containing 968 loci including 516 known or predicted gene sequences, 317 STSs not included in these sequences, and 135 nonexpressed multinucleotide polymorphisms. The published sequence spans 34.6 Mb, inclusive of gaps estimated to total 1.1 Mb, compared with a top-down estimate of 43 Mb. This discrepancy is discussed, but will not be resolved until more of the genome is analyzed. The radiation hybrid map has 5% error in order and 34% error in location exceeding 1 Mb. The utility of a composite location based on evidence other than sequence is limited to regions not yet sequenced. A genetic map conditional on sequence order was constructed from pairwise lods. its length of 74.8 cM in males and 80.2 cM in females is slightly less than the previous estimate not constrained by sequence order. Five recombination hot spots are detected, with differences in location between the sexes. Male recombination correlates with repetitive DNA, whereas female recombination does not. It remains to be seen whether this is true for other human chromosomes. An algorithm to improve the fit of cytogenetic bands sequence location reduces the discrepancies in cytogenetic assignment from 61 to 38. This sequence-based integrated map is represented in the genetic location database (LDB2000), which is available at http://cedar.genetics.soton.ac.uk/public_html/LDB2000. html.