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Mouse to man: The story of chromosomes

The complete sequencing of human chromosome 17 and mouse chromosome 11 offers unique insights into the evolution of the genome of higher mammals, said a Baylor College of Medicine researcher who participated in this effort reported in today’s issue of the journal Nature.

The work represents the first time that a mouse chromosome has been completely sequenced and annotated, said Dr. James R. Lupski, vice chair and professor in the BCM department of molecular and human genetics and professor of pediatrics. This presented scientists with the opportunity to examine intensively the similarities and differences in the DNA sequence of human and mouse.

Lupski was brought into the work while he was on sabbatical at the Wellcome Trust Sanger Institute in Cambridge, England, last year. The Sanger Institute and the Broad Institute of MIT and Harvard were the primary institutions involved in the sequencing effort. However, scientists at Sanger dubbed a portion of chromosome 17 the Lupski segment because he has spent so much time dealing with that portion of the genome in his effort to identify gene mutations that result in disease. They sought his expertise on the chromosome.

Chromosome 17 is particularly rich in disease genes such as BRCA1 (the first identified breast cancer gene); NF1 (neurofibromatosis); the gene associated with repairing DNA damage that might otherwise result in cancer (TP53); Smith-Magenis syndrome (SMS), and Charcot-Marie-Tooth type 1A10 (the most common type of inherited nerve disorder [CMT1A]).

The study of this chromosome gives a clearer picture of how genome changes through evolution, Lupski said. For example, breaks in synteny or the maintenance of the order of genes between species coincide with changes in the architecture of the chromosome itself. In some cases, DNA repeats get in the way. In others, there are rearrangements of the genome that occur during the process of cell reproduction.

"As we go up the mammalian line, and particularly in primate, it is obvious that rearrangement in the genome is the predominant force in the evolution of genomes," said Lupski. That is particularly evident in this report that allows carefully comparison of the mouse and human chromosomes.

"Perhaps one way to evolve faster is not by making changes in base pairs (the chemicals that make up DNA), but by changing chunks of genome," said Lupski.

The sequencing of chromosome 17 and mouse chromosome 11 was an international effort involving researchers from around the globe.

Ross Tomlin | EurekAlert!
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