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Difference in Gene Numbers Responsible for Wide Variations in the Human Genome

When scientists announced in 2003 that they had finished the Human Genome Project, they were quick to clarify that sequencing of the full human genome not yet complete. As much as six percent of the genome was beyond the reach of available technology, leaving regions on the 23 pairs of human chromosomes unsequenced.

For the last seven years, Howard Hughes Medical Institute researcher Evan Eichler has been working on part of that unfinished business. It turns out that one of the reasons the genome sequencers could not deliver a fully sequenced and annotated genome is that about five percent of the human genome contains duplicated genes. Eichler, who is one of the world’s foremost experts on gene duplication, has showed that the human genome changes constantly—and duplicate sequences are among the fastest evolving regions.

Now Eichler, who is at the University of Washington School of Medicine, has teamed with graduate students Jacob Kitzman and Peter Sudmant and colleagues from the University of Washington and Agilent Technologies Inc. to sort out much of that duplication. In an article published in the October 28, 2010, issue of Science, Eichler’s team provides a new highly detailed analysis of gene duplication across the human genome. By analyzing duplicate genes in the genomes of 159 people, including some from the Yoruba people of Nigeria, Utah residents with ancestors from northern and western Europe, Japanese people, and Han Chinese, the researchers uncovered wide variation in gene copy number both within groups and between groups – far more than anticipated. The variability, Eichler said, affects many genes that play a critical role in brain development. It also helps tell the story of human evolution, and may provide important clues into disease development.

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