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The Genomic Neighborhood

A family with multiple members with syndactyly is helping researchers understand the role of topologically associating domains and genomic architecture, the New York Times reports.

Topologically associating domains, or TADs, are linear regions of the genome that fold into three-dimensional structures that mostly interact within the neighborhoods they've formed.

"Genes and regulatory elements are like people," Job Dekker from the University of Massachusetts Medical School tells the paper. "They care about and communicate with those in their own domain, and they ignore everything else."

But as the Times notes, when these neighborhood barriers are breached, things can go awry as parts of the genome that typically don't interact, do. TAD defects have been linked to cancer and other diseases and may also have a role in developmental disorders, including the anonymous family's syndactyly.

The Max Planck Institute for Molecular Genetics' Stefan Mundlos and his colleagues have found that disruptions to TAD boundaries in model organisms can lead to limb malformations. "If a muscle gene turns on in the cartilage of developing digits," he says, "you get malformations."

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