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Same Genes, Different Doses
Distant DNA controls gene activity

Context: Even in cases where two people share the same gene, they can produce widely differing amounts of the protein the gene codes for. This can lead to differences in physical characteristics, and it can also mean the difference between sickness and health. Segments of DNA called regulatory elements are one factor controlling how much of a particular protein the body produces. While researchers today can use algorithms to pick out genes from sequences of DNA, they have previously been unable to accurately distinguish regulatory elements from other non-coding DNA, let alone match those elements with the genes that they regulate. Researchers at the University of Pennsylvania, led by Vivian Cheung, have found a way to do just that.

Methods and Results: Using white blood cells from 94 people, the researchers identified more than 3,500 genes whose expression was similar among relatives but varied widely among people who were unrelated. These patterns of expression were then correlated with patterns of known genetic markers across the genome. Hundreds of genes’ expression was linked to particular genetic markers – far more than the number predicted by chance. About four-fifths of these markers were located more than 5,000 base pairs from the genes that they regulated; many were even on other chromosomes. Researchers found that some “hot spot” regions apparently influence the expression of more than 30 genes. In addition, many genes seem to be regulated by more than one region.

Why it matters: Researchers can finally study the genetic differences governing gene expression. The hot spots, which Cheung’s team calls “master regulators,” will help to tease out some of the mysteries that surround gene expression. More immediately, the techniques may allow researchers to use variation within genes and within regulatory elements to understand and treat disease. For years, geneticists have scoured the human genome for genes that contribute to complex traits, like susceptibility to depression or heart disease. Finding factors that control the genes is just as important but much more difficult. Now scientists should be better equipped to find the genetic variations that make a difference in matters of life and death.

Source: Morley, M. et al. (2004) Genetic analysis of genome-wide variation in human gene expression. Nature 430:743-7.

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Tagged: Biomedicine

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