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Millions of new regulatory elements found in human genome

October 13, 2011

An international research team led by Kerstin Lindblad-Toh at the Broad Institute, US and Uppsala University, Sweden has mapped and compared the genomes of 29 mammals. The findings, published in Nature, reveal millions of new regulatory elements in the human genome that in various ways govern how proteins are formed. The new knowledge is important for our understanding of how mutations in human genes give rise to diseases.

The human genome was mapped some ten years ago, but its function has been difficult to understand. Recent comparisons with mice, rats, and dogs, have shown that humans have more than 20,000 genes. However, it has been difficult to find the elements in the genome that determine when, where, and how genes produce proteins.

By comparing a large number of mammals, scientists have now created a catalogue of millions of regulatory elements found both between and within genes. These elements are incredibly important in making us humans into the complex organisms that we are, even though our genes are rather similar to those of other vertebrates," says the lead author of the study, Kerstin Lindblad-Toh, Scientific Director of Vertebrate Genome biology, at the Broad Institute in the US and professor of comparative genomics, Uppsala University, Sweden.

Human genes constitute only about 1.5 percent of the genome, whereas regulatory elements appear to take up about three times as much space. The researchers have now been able to show where a majority of these regulatory elements are located in the genome. By studying patterns in these elements, and combining this information with other types of genetic data, they have been able to understand how many of these regulatory elements function.

"The elements we find can have entirely different functions. They can make different cell types use different versions of a certain gene, or can turn off a gene if the concentration of a certain compound is too high in a cell. Above all we see that proteins that govern fetal development and the function of the nervous system have a huge number of regulatory elements," says Kerstin Lindblad-Toh.

The regulatory elements that were found in this comparison between 29 mammals are important for many of our central functions, which are shared by placental mammals. However, the scientists were also looking for how these elements changed over time in various groups of mammals as they adapted to different living conditions.

"Among other things, we can see what parts of proteins and what regulatory elements changed rapidly in primates and humans. With the help of about a hundred other mammal species, we believe we will understand the function of every key base in the human genome and get a better understanding of how changes in genes made rodents into rodents and primates into primates," says Kerstin Lindblad-Toh.

Uppsala University


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