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Columbia geneticists uncover new gene involved in determining hair texture and density in humans

Findings may lead to new treatments for excessive or abnormal hair growth

A Columbia University Medical Center research team has discovered a new gene involved in determining hair texture in humans. The team's genetic analysis demonstrated that mutations in a gene, known as P2RY5, cause hereditary "woolly hair" — hair that is coarse, dry, tightly curled and sparse.

"Our findings indicate that mutations in the P2RY5 gene cause hereditary woolly hair. This is significant as it represents the discovery of the first new gene whose primary function seems to be the determination of hair texture in humans," said lead author Angela M. Christiano, Ph.D., the Richard and Mildred Rhodebeck Professor of Dermatology and Genetics & Development, at the Columbia University College of Physicians and Surgeons.

"This genetic finding may inform the development of new treatments for excessive or unwanted hair, or potentially hair growth." added Dr. Christiano.

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Findings were published in an online edition of Nature Genetics at 1 p.m. EST on Sunday, February 24, 2008. The paper will appear in the journal's March print issue.

The genetic causes of hair texture in humans are largely unknown. Hair shafts emerge from the surface of the skin and display wide variability in texture and color among individuals of different populations around the world.

Since research has shown that woolly hair was common among Pakistani families, Dr. Christiano and her colleagues set out to determine why this type of hair was specific to this group of people. They hoped that finding the genetic basis of this unique type of hair would help them to distinguish other genetic hair types, and to learn more about the genetic underpinnings of different hair textures.

Much of Dr. Christiano's research has focused on dermatologic variants found in Pakistani families, as they often represent ideal subjects for genetic analyses as they tend to be relatively homogeneous, with close-knit families that tend to live nearby one another, and often intermarry.

To identify a gene involved in controlling hair texture, Dr. Christiano and her team performed a genetic analysis of six families of Pakistani origin, who all shared hereditary woolly hair. The cause of hereditary woolly hair was found to be a mutation in a gene called P2RY5. Until this discovery, the pathogenesis of hereditary woolly hair had been largely unknown.

As the authors write in the paper, "The bulb region of plucked hairs from woolly hair patients showed irregular bending without attachment of the root sheath." They propose that mutations in P2RY5 most likely result in hair follicle disruptions, which then compromise its anchoring to the hair shaft and cause the abnormal bending of the bulb region, leading to woolly hair.

Dr. Christiano's discoveries have led to the identification of several genes controlling human hair growth. It remains to be determined whether common variants on the P2RY5 gene can also contribute to naturally occurring variations in hair texture between different human populations.

According to the researchers, P2RY5 is the first gene of a type known as a G-protein coupled receptor (GPCR) implicated in a human hair disorder — thereby making it possible to develop drugs that target this receptor. GPCRs represent the largest known class of molecular targets with proven therapeutic value. It is estimated that more than 40 percent of existing drugs work by targeting GPCR drug targets; this target class represents a large fraction of the total biological targets against which FDA-approved oral drugs are directed. Of the top 200 best-selling prescription drugs more than 20 percent interact with GPCRs, providing worldwide sales of over $20 billion.

Elizabeth Streich | EurekAlert!
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