Uncovering genes that orient organs

Our bodies exhibit symmetry—two eyes, ears, arms, legs, and so on. But internal organs such as the heart, liver, and stomach must develop asymmetrically to function normally. In heterotaxy (Htx), a rare and potentially deadly birth defect, left – right asymmetry is disrupted, causing organs to be malformed or in the wrong position.

In a new genomic study published online January 31 in Proceedings of the National Academy of Sciences, Htx patients were found to be twice as likely as control subjects to harbor copy number variations (CNVs), stretches of duplicated or missing genetic material. Many genes disrupted by these CNVs have counterparts in the frog Xenopus tropicalis, and when the authors knocked out Xenopus genes they thought might be involved in left–right patterning, they identified five that are essential for proper development, none of which had previously been tied to asymmetry.

“Combining human genetics with model systems such as the frog will allow us to rapidly identify genes that affect embryonic development and better understand the causes of these childhood diseases,” says co-author Mustafa K. Khokha, M.D., associate professor of pediatrics and genetics.