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How we use mom's and dad's genes

Sep 29, 2016

Researchers at Ludwig Cancer Research and the Karolinska Institutet in Stockholm have characterized how and to what degree our cells utilize each copy—or allele—of each gene pair inherited from our mother and father. The study, led by Ludwig Stockholm’s Rickard Sandberg, sheds light on why identical twins can appear different even though their genes are identical and why many genetic disorders vary so much in their manifestation.

Because allele pairs, one of which is inherited from each parent, have slight differences in their DNA sequence, variations in the expression of each allele can have functional consequences in tissues. But it has been unclear whether the “choice” of which allele a cell should express is forwarded through cell division, as cells generate clonal descendants—or if it takes place independently in each cell over and over again. Each scenario would result in a different outcome: The first results in patches of cells having the same set of expressed alleles; the second in allelic expression patterns that “flicker” randomly between alleles from cell to cell.

To address this issue, Sandberg and his colleagues applied single-cell RNA-sequencing to characterize the dynamics of gene copy expression in mouse and human cells. They report in Nature Genetics that the expression of a gene fluctuates dynamically between each allele from cell to cell, unaffected by whether or not cells are of the same clonal family. Only as few as 0.5% to 1% of genes are fixed into expressing just one of the alleles.

The complete release from which this summary is adapted is available here.

A release on Sandberg’s previous work in this area, published in Science, is available here.