Rare hunting dogs’ unique noses may offer clue to cause of cleft lip and palate in humans

It’s not entirely understood why some children are born with orofacial clefts, such as cleft lip or palate. But a new study suggests a genetic clue may be found in a rare breed of hunting dog.

An international research team reports that it identified the genetic origins of the forked nose that distinguishes Turkish Pointers – or Catalburun – a breed that have been prized for their supposed superior sense of smell. Publishing in the scientific journal Genome Research, the researchers traced the dogs’ forked, or bifid, nose to a mutation of the gene PDFGRA.

Peter Savolainen, a canine genealogy authority at Stockholm’s KTH Royal Institute of Technology, says the study raises the possibility that there may be a connection between the mutation of PDFGRA and cases of human orofacial clefts.

One indication is in the role PDFGRA was previously found to play in embryonic development of mice. PDFGRA is essential for connecting the halves of the mouth and nose during embryonic development, the study stated.

“This indicates that the gene might be involved in some cases of human orofacial clefts,” Savolainen says. “While there are several genetic and environmental reasons behind orofacial clefts in humans, this study offers a clue to another factor.”

A mutated variant of PDFGRA was also found to be behind unexpected forked-nose deformities in other breeds of dog. The researchers also found two mutations in another gene, LCORL, which code for large breeds and small breeds, respectively.

The work was a collaboration between KTH Royal Institute of Technology, the U.S. National Human Genome Research Institute; University of Ankara; Afyon Kocatepe University and University of Selcuk in Turkey; Utrecht University in the Netherlands; University of Helsinki and Folkhälsan Research Center in Finland; Cornell University in Ithaca, New York; and Embark Veterinary in Boston, Massachusetts.

Savolainen says the research demonstrates how studying the smaller gene pool of bred dogs provides valuable genomic insights for medical science. “Studying the very inbred dog breeds is an excellent tool for finding the genetic reason for many morphologic traits and diseases in humans,” he says.

“In humans there is just too much genetic variation, making it hard to identify exactly which genetic mutation causes a specific disease,” he says.

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