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Found: Missing sequence of the human Y chromosome

Scientists report today in the journal Genome Research that they have successfully cloned and characterized a previously intractable DNA sequence: a 554-kilobase-pair genomic segment near the centromere of the human Y chromosome. This sequence contains eight putatively active genes that could be implicated in sex-associated height differences and gonadal tumor development.

This pericentromeric gap was one of the few holes remaining in the "finished" sequence of the human genome reported last October by the International Human Genome Sequencing Consortium. This "finished" sequence was the culmination of a 13-year effort to elucidate the order and orientation of 2.85 billion basepairs that comprise the human genome. The high-quality sequence spanned more than 99% of the euchromatic (gene-containing) portion of the genome with an accuracy of 99.999%, but despite this accomplishment, substantial sections of chromosomal sequences were still missing. The Y chromosome, a sex chromosome that is specific to the human male, has posed a particular challenge to researchers attempting to decode its sequence. It contains an extraordinary abundance of repetitive elements, including transposons and tandem arrays of satellite sequences. This highly repetitive, transcriptionally dormant genomic landscape, termed "heterochromatin," defines approximately two-thirds of the Y chromosome, including a section spanning the centromere. Such repetitive sequences, although not recalcitrant to cloning, are laborious to assemble, requiring meticulous analysis of complex repeated sequences. In this case, the challenge was undertaken by a team of scientists led by Gudrun Rappold, Ph.D., Professor of Human Genetics at the University of Heidelberg in Germany. Their manuscript describing this work, published online today and in the February print issue of Genome Research (www.genome.org), presents the sequencing and analysis of 554 kilobases of previously uncharacterized sequence from the peri
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Source:Cold Spring Harbor Laboratory


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