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Lineage trees for cells

l division, the task would be impossible.

The study focused on mutations in specific mutation-prone areas of the genome known as microsatellites. In microsatellites, a genetic "phrase" consisting of a few nucleotides (genetic "letters") is repeated over and over; mutations manifest themselves as additions or subtractions in length. Based on the current understanding of the mutation process in these segments, the scientists proved mathematically that microsatellites alone contain enough information to accurately plot the lineage tree for a one-billion-cell organism.

Both human and mouse genomes contain around 1.5 million microsatellites, but the team's findings demonstrated that a useful analysis can be performed based on a much smaller number. To obtain a consistent mutation record, the team used organisms with a rare genetic defect found in plants and animals alike. While healthy cells have repair mechanisms to correct copying mistakes and prevent mutation, cells with the defect lack this ability, allowing mutations to accumulate relatively rapidly.

Borrowing a computer algorithm used by evolutionary biologists that analyzes genetic information in order to place organisms on branches of the evolutionary tree, the researchers assembled an automated system that samples the genetic material from a number of cells, compares it for specific mutations, applies the algorithm to assess degrees of relatedness, and then outlines the cell lineage tree. To check their system, they pitted it against the tried-and-true method of observing cell divisions as they occurred in a lab-grown cell culture. The team found that, from an analysis of just 50 microsatellites, they could successfully recreate an accurate cell lineage tree.

While the research team plans to continue to test their system on more complex organisms such as mice, several scientists have already expressed interest in integrating the method into ongoing research in thei
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Contact: Elizabeth McCrocklin
EMcCrocklin@jgordonassociates.com
212-871-3020
American Committee for the Weizmann Institute of Science
27-Oct-2005


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