MUTATION ASSOCIATED WITH CLEFT PALATE IDENTIFIED
Scientists studying
birth defects in humans and purebred dogs have identified an association
between cleft lip and cleft palate -- conditions that occur when the lip and
mouth fail to form properly during pregnancy -- and a mutation in the ADAMTS20 gene. Their findings were presented
at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San
Diego.
"These
results have potential implications for both human and animal health, by
improving our understanding of what causes these birth defects in both
species," said Zena Wolf, BS, a graduate student at the University of
California, Davis School of Veterinary Medicine.
In
both humans and dogs, cleft lip and cleft palate occur naturally with varying
degrees of severity, and can be caused by various genetic and environmental
factors. Since purebred dogs breed only with each other, there is less genetic
variation to consider, making cleft lip and cleft palate easier to understand
in these populations, Ms. Wolf explained.
From
previous studies, the researchers knew that a mutation in the dog genes DLX5and DLX6,
which are involved in face and skull development, explained 12 of 22 cases of
cleft palate. However, a mutation in the corresponding human genes accounted
for just one of 30 cases in the study sample.
To
search for additional genes that may be involved, Ms. Wolf and colleagues
performed a genome-wide association study (GWAS), a study that compares the
genomes of dogs with cleft lip and cleft palate to those of dogs without it.
They found that the conditions were associated with a mutation in the gene ADAMTS20 that caused the protein it encodes to
be shortened by 75 percent. Previous studies had shown that ADAMTS20 is involved in the development and
shaping of the palate, but no specific mutations that occur in nature had been
identified. A similar GWAS in people with cleft lip and cleft palate suggested
that mutations in the human version of the ADAMTS20 gene may also increase the risk of
these conditions.
"Cleft
lip and cleft palate are complex conditions in people, and the canine model
offers a simpler approach to study them," Ms. Wolf said. "Not only
does this research help people, but it helps dogs, too," she added.
The
study was conducted by scientists at the University of California, Davis, along
with collaborators at the University of Pittsburgh, the University of Iowa, and
the University of Sydney.
Future
directions include searching for additional genes that may be associated with
cleft lip and cleft palate, and extending the research to other breeds of dogs,
such as Labrador Retrievers and Whippets.
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