ASHG 2008: Copy number variations and their effects on the brain
Geneticists are taking an increasing interest in copy number variants (CNVs), genetic sequences that can be repeated or deleted from individual to individual. I might have two copies of a gene, while my wife might have three. These are a major source of genetic variation and have been implicated in contributing to important diseases. Alexandre Reymond of the University of Lausanne explained work he’s been involved with to characterize CNVs in mice. Looking at lab strains and several wild mice, they uncovered nearly 3000 of them. Then to understand how these CNVs might be affecting phenotype, they looked at gene expression in different tissue types in the mice to see if genes in and around those CNVs might be differentially expressed depending on how many copies there were. In five out of six tissue types they tested, as many as 2/3 of the CNVs they looked at were differentially expressed. The brain only showed 1/3 of CNVs affecting gene expression and generally doing so in a negative fashion. They found that genes far away from the actual CNVs could be affected, and one experiment suggested that the effects could span 10s of millions of basepairs, affecting the expression of quite distant genes. They also looked at expression during different developmental stages in the mice for brain and liver and found that while expression for 2/3 of genes in CNV regions were always affected in liver, brain CNVs appeared to be controlled differently at different developmental stages. Their findings had several people asking about how epigenetic changes like histone tail modifications might be influencing expression changes. I wonder how the brain specific differences square with discoveries linking CNVs to autism and schizophrenia in humans. Might there be a mechanism to protect the brain from CNVs that goes haywire for those affected?
