Researchers identified two genes in genomic region linked to autism

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genetic/phenotype connections

Genes

Scientists documented a direct link between deletions in two genes, fam57ba and doc2a, in zebrafish and certain brain and body traits.

“Finding the molecular connections between a brain and a body phenotype is indeed really paradigm shifting,” says Whitehead Institute Member Hazel Sive. The study tells about the common control of these two aspects of phenotype, which is very interesting and useful for developing therapies for these phenotypes.

Both genes reside in the 16p11.2 region of human chromosome 16. Around 4 million people worldwide, have deletions in this region, and these deletions associated with multiple brain and body symptoms, including autism spectrum disorders, developmental delay, intellectual disability, seizures, and obesity.

Scientists have had difficulty teasing apart the relationship between specific traits and deletions in this region. It includes at least 25 genes, and there is not a one-to-one mapping of the gene to phenotype. Instead, multiple genes seem to create a web of interactions that produce a variety of characteristics.

genetic/phenotype connections

The Sive group uses zebrafish to study the genetic/phenotype connections associated with human disorders. Like the human genome, the zebrafish genome has two copies of each gene, and scientists can remove the function of multiple genes to produce phenotypes that reminiscent of human symptoms.

The results on zebrafish indicate that two genes in the 16p11.2 region could be key for brain development.

Researchers investigated further by deleting one copy of fam57ba and doc2a individually, the effect is minimal. However, simultaneously removing a copy of both genes revealed significant synergy between them. Compared with controls, fish with only one copy of each gene exhibit hyperactivity, increased propensity for seizures, body and head size, and fat content.

When both copies of only fam57ba are removed, the fish are much larger and with a higher fat content.

The mechanisms underlying this brain/body connection still not well understood. One of the identified genes provides some intriguing hints as to how metabolism and brain function could intertwine. The lipid type, ceramide, also has a functional role in various signaling pathways and affects synaptic function. Although its primary role is not in the synapse, but providing structure in cell membranes.

For Sive, the two identified genes could be just the beginning. Our data suggest that there may be metabolic genes involved in human neurodevelopmental disorders.

More information: [Whitehead Institute]

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