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Found: Missing sequence of the human Y chromosome

centromeric region of the Y chromosome. This sequence contains a 450-kilobase "euchromatic island" with eight presumably active genes flanked by repetitive satellite sequences. To ensure that this 554-kilobase sequence was in fact missing from the "finished" human genome sequence and was not a structural polymorphism present only in a subset of males in the human population, members of Rappold's laboratory ?including Stefan Kirsch, Ph.D., lead author on the paper ?tested 100 men of different ethnic origin for the presence of this 554-kilobase fragment. Indeed, the sequence was present in all 100 individuals tested, but not in any female controls, confirming that this sequence was a fundamental part of the Y chromosome. More surprising, however, was Rappold's finding that this "missing" sequence was not unique to the Y chromosome. Rather, this sequence exhibited between 95-99% homology to sequences on exactly half (11 of 22) of the other chromosomes in the human genome, including the pericentromeric regions of autosomes (non-sex chromosomes) 1, 2, 3, 4, 9, 10, 11, 14, 15, 16, and 22. This remarkable similarity can be attributed to segmental duplications, a phenomenon whereby large portions of the genome are copied during evolution. Segmental duplications, which emerged during the past 30 million years of primate evolution, are significantly enriched in subtelomeric and pericentromeric sequences, and now comprise approximately 5% of the human genome, were considered to be one of the biggest obstacles to finishing the human genome sequence. "The identification of these segmental duplications suggests an underrepresentation of pericentromeric regions of the acrocentric chromosomes in the current human genome sequence," Rappold pointed out. The current study was designed as part of a long-term effort to characterize the molecular genetic basis for Y-chromosome-linked phenotypes. Rappold and colleagues had previously physically mapped the GCY locus, which is thought to be
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Source:Cold Spring Harbor Laboratory


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