A break for bone disease research

July 29, 2011, RIKEN
Figure 1: In the Japanese population a specific gene is linked to osteoporosis that can lead to broken bones in the elderly. Credit: 2011 iStockphoto/lisegagne

Osteoporosis is the reduction in bone strength that occurs during aging, which increases the chance of elderly people experiencing breaks. A genome-wide association study in the Japanese population has revealed that a genomic variant within a newly identified gene, which the discoverers have named FONG, enhances susceptibility to osteoporosis.

Led by Shiro Ikegawa of the RIKEN Center for Genomic Medicine, the researchers began by examining the entire genomes of 190 Japanese individuals with osteoporosis and 1,557 controls. Based on the results of this initial study, they focused on 3,000 single nucleotide changes in the genomes of an additional 526 individuals with osteoporosis and 1,537 controls. Additional analyses in two further population samples led to the identification of the genomic variant, found on chromosome 2; however, there was no known gene around the variant. Instead, the researchers found only representations of portions of expressed in the form of several expressed sequence tags.

By analyzing messenger RNAs (mRNAs) expressed from the genomic region around the variant, Ikegawa and colleagues discovered that the genomic variant is within FONG, which stands ‘formiminotransferase N-terminal sub-domain containing gene’. This previously unknown gene is expressed in various human tissues, including bone. Because the genomic variant resides outside of the FONG protein-coding region, Ikegawa and colleagues hypothesized that the variant may somehow affect the expression levels of the FONG gene. 

One domain of the FONG gene, the formiminotransferase N-terminal sub-domain, is common in many different species, which indicates that it could have a very important function for maintaining life. “This domain appears to be an enzyme that is responsible for converting the amino acid histidine to the amino acid glutamic acid,” says Ikuyo Inaba (nee Kou), a researcher in Ikegawa’s laboratory and the first author of the study. 

Glutamic acid and its breakdown products are known to play an important role in maintaining the bones, so any problems with the creation of these compounds may lead to osteoporosis. “The glutamic acid signaling pathway may also affect osteoporosis risk in non-Japanese individuals,” she explains. “So, the association of this variant of the FONG gene with disease in other populations is worth investigating in the future.”

According to Inaba, further work is needed to determine how the osteoporosis-linked variant of the FONG gene can affect its expression. The identification of this variant in FONG—and its link to —can aid in the development of new therapies for this disease.

Explore further: Pinpointing a tell-tale mark of liver cancer

More information: Kou, I., et al. Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. PLoS ONE e19641 (2011). doi:10.1371/journal.pone.0019641

Related Stories

Pinpointing a tell-tale mark of liver cancer

July 8, 2011
Persistent hepatitis C virus (HCV) infection can lead to chronic hepatitis C and then progress to fatal liver diseases including liver cirrhosis and liver cancer, the third most common cause of cancer-related deaths. Worldwide, ...

Common genetic variant linked to pulmonary fibrosis risk

April 20, 2011
Scientists funded by the National Institutes of Health have identified a common genetic variant associated with substantially increased risk of developing pulmonary fibrosis, a debilitating and life-threatening lung condition. ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.