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Ultraconserved elements in the genome: Are they indispensable?
Date:9/4/2007

o sequence changes in these regions. The results of this study clearly show that this is not the case. While I don't think we can conclude that the mice we created with the ultraconserved elements deleted are normal, we can confidently conclude that the presence of the ultraconserved elements are not required for the viability of the organism."

Choosing the sequences

Some of the 481 ultraconserved sequences in humans, rats, and mice are coding sequences, genes that code for proteins, but over half, termed noncoding ultraconserved elements, are not. Previous studies by the Berkeley Lab researchers and their colleagues have suggested an important role for these noncoding sequences in gene regulation; because they act to promote the expression of genes they are known as "enhancers."

For this study the team specifically chose four ultraconserved noncoding elements, thought to be enhancers of nearby genes that when mutated lead to severe developmental abnormalities or fertility problems.

For example, noncoding ultraconserved element number 467 (uc467) has 731 base pairs of sequence that are identical among human, mouse, and rat; it is one of the longest of all ultraconserved elements within our genome. Uc467 is thought to be an enhancer for ARX, a gene that, when defective in mice, disturbs male sexual development and causes lethal brain abnormalities, and in humans causes a wide range of neurological and sexual-development disorders.

Using standard mouse genetic-engineering techniques, the researchers prepared four lines of knockout mice, each type lacking one of the chosen ultraconserved elements.

"We knew that knocking out the genes themselves leads to lethality or sexual abnormalities in mice, and sometimes other problems," says Ahituv. "So we expected that mice lacking the ultraconserved sequences that are thought to regulate these genes would produce a similar result: lethality or infertility."


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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert

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