The causes of neural tube defects, which include the birth defects anencephaly and spinal bifida, have confounded scientists for some time now. But looking into similar defects among Weimaraner dogs has exposed a gene that can be found in humans as well, a new study says.

Neural tube defects affect more than 300,000 babies each year. They affect the brain, spine, or spinal cord, often occurring before a pregnant woman even knows she's pregnant. In spinal bifida, the spinal column doesn't close completely — this can cause some paralysis in the legs. In anencephaly, most of the brain or skull don't develop, resulting in stillborn death or death shortly after birth.

"The cause of neural tube defects is poorly understood but has long been thought to be associated with genetic, nutritional, and environmental factors," Noa Safra, lead author of the study and a postdoctoral fellow at the University of California Davis School of Veterinary Medicine, said in a statement.

The team of researchers mapped the genomes of four Weimaraner dogs with spinal dysraphism, a spinal-cord abnormality that can cause any combination of impaired motor coordination, partial paralysis in the legs, abnormal gait, crouched stance, and abnormal leg or paw reflexes. They also mapped the genomes of 96 other Weimaraners that had no neural tube defects.

When analyzing the genome, they found that a part of canine chromosome eight had mutated, specifically in the gene called NKX2-8. This gene is part of a larger group of genes known as "homeobox" genes, and they've been associated with anatomical development in the embryo.

They also found that this gene mutated in about 14 out of every 1,000 dogs, and that this particular gene mutation only occurred in Weimaraners.

"The data indicate that this mutation does not appear as a benign mutation in some breeds, while causing defects in other breeds," Safra said. "Our results suggest that the NKX2-8 mutation is a 'private' mutation in Weimaraners that is not shared with other breeds."

To see the human connection with NKX2-8, the researchers also sequenced 149 different samples of spinal bifida from humans. They found six cases in which patients carried mutations of the gene. However, they stress that further studies are needed to determine that the gene is responsible for neural tube defects.

Safra also noted that because dogs receive similar medical care and household living conditions when compared to humans, they provided a good model to study. Additionally, many neural tube defects are known to occur naturally in dogs.

Washington state recently saw a four-fold increase in anencephaly defects, with nearly eight out of every 10,000 births resulting in the disorder. It's often attributed to the mother's poor consumption of folic acid — a vitamin required to produce new cells — before and during pregnancy, but can also happen as a result of other medical factors, including obesity and diabetes. State officials who tried to determine causation said they needed more cases to examine before they could determine the cause conclusively.


Safra N, Bassuk A, Ferguson P, et al. Genome-Wide Association Mapping in Dogs Enables Identification of the Homeobox Gene, NKX2-8, as a Genetic Component of Neural Tube Defects in Humans. PLOS One Genetics. 2013.