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Exceptional Chromosome Regions II

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An HGP Program Perspective

Marvin Stodolsky
U.S. Department of Energy
Marvin.Stodolsky@science.doe.gov

The existence of chromosomal regions with exceptional structures and or posing exceptional analytical problems has been manifest, since the recognition of telomeres and centromeres. Over time, the definition of these ECR have become more precise, with several contributions from within the DOE HGP. Robert Moyzis recognized the repeating sequence of the telomere tips. This led to strategies for their cloning with Bob's follow though into the sequencing of the near telomeric regions. When BAC resources began to mature in Mel Simon's lab, Julie Korenberg with Xiao-Ning Chen used FISH to characterize the resource. I recall the feeling of relief during the next HGP Workshop, from the result that any chimerism of the resource was not worse than 5%, as compared to the common chimerism of YAC resources. I recall feeling of mild terror, as it became progressively apparent that much of the 5% represented real duplications/replications. A 5% of 3.5 megabases was potentially a Lot of Trouble. Barbara Trask's FISHing added the complication, that there was heterogeneity in the human population with respect to the duplication pattern of the near telomeric sequences across the chromosomes. In the course of mapping a fragile X site, David Nelson's team discovered that a copy had been transposed to a near centromeric region of chr22. It has become progressively more apparent, that the centromeric regions are relative hotbeds for acquiring distant genes, reshuffling them locally, and with occasional flings to distant regions of the genome. Detail on these dynamics has been filled in by Evan Eichler and collaborators. While coverage of the genome by BACs and Pieter de Jong's PACs was manifestly good, both teams had recognized a few holes and unstable clones. Natasha Kouprina and Vladimir Larionov are now achieving a rough quantitation of their prevalence. Perhaps it is fortunate that the ECR couldn't be quantitated earlier, as it might have been necessary to acknowledge a very rough Battle in Progress as contrasted to a Victory in Hand.



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