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Sex chromosome shocker: The 'female' X a key contributor to sperm production
Date:7/21/2013

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To set the sequence straight, the lab turned to the unique sequencing method Page had developed with collaborators at Washington University in St. Louis to help navigate the structural complexities of the Y chromosome. As Page reported roughly a decade ago, the Y contains several regions of large palindromesareas of mirror-imaged genetic sequences. Such regions defy elucidation via conventional sequencing approaches, which simply cannot detect extremely subtle genetic differences found hidden among the "mirrors." In response, Page and colleagues devised what is known as SHIMS (single-haplotype iterative mapping and sequencing) to establish a definitive reference DNA sequence of the Y chromosome.

Using SHIMS, the lab greatly improved the human X reference sequence, accurately assembling three large amplicons, identifying previously unknown palindromes, and ultimately shortening the entire length of the sequence by eliminating four major gaps. These important updates will now be incorporated into the reference sequence of the human X for use by the greater scientific community.

Upgraded reference in hand, the lab discovered that, as might have been expected, the mouse and human X chromosomes have nearly 95% of their X-linked, single-copy genes in common. Almost all of these genes are expressed in both sexes. Strikingly, however, the lab identified approximately 340 genes that are not shared between the two species. Fittingly, most of these genes reside in ampliconic regions of the X and appear to have been acquired independently during the 80 million years since mouse and human diverged from a common ancestor. Expression analyses revealed that these genes are active almost exclusively in testicular germ cells, where, at a minimum, they likely contribute to sperm production. Further exploration of these X-ampliconic regions and their associated genes is warranted.

"This is a collection of genes that has largely eluded medical genet
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Contact: Matt Fearer
fearer@wi.mit.edu
617-452-4630
Whitehead Institute for Biomedical Research
Source:Eurekalert

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