Study discovers new genes for rare inherited diseases

September 6, 2011, CORDIS
EU-funded study discovers new genes for rare inherited diseases

An international team of researchers has identified two new genes connected with hereditary renal diseases.

Altogether the team studied 850 proteins likely to be involved in 3 genetic ciliary diseases: nephronophthisis, Joubert syndrome and Meckel-Gruber syndrome. They mapped how these proteins interact to predict which of them play a crucial role in the diseases, something which led to the double .

Ciliary diseases are caused by to a part of the cell called the . The cilium is crucial as it is involved with cell signalling pathways during cell development in different parts of the body. Cilia are protrusions of cells that have different functions: for example, cilia in the take care of transporting , whereas cilia in the kidneys sense urine flow. Improper cilia development can result in various diseases.

However our knowledge of cilia composition, wiring, dynamics and the associated signalling pathways of the corresponding molecular and associated protein networks remains very limited.

Writing in the journal Cell, the team explains how they conducted their research on a family in Pakistan, in which four siblings had Joubert syndrome: they combined gene-mapping techniques with the use of a map, thereby identifying the TCTN2 gene, which when defective, leads to onset of the condition. The syndrome occurs when a child receives the gene from each parent.

Joubert syndrome affects brain functioning and results in intellectual deficits, movement and coordination problems, and other symptoms such as kidney and . This syndrome is reported to affect approximately 1 in 100,000 children, although scientists believe this figure could be way off the mark since the disease could be affecting far more children worldwide.

So far, 10 genes have been connected with Joubert syndrome. One of the study authors from Canada's Centre for Addiction and Mental Health (CAMH) previously discovered the CC2D2A gene, which accounts for about 9% of Joubert syndrome cases.

"A defect in any aspect of this molecular pathway may have very similar effects at the clinical level," comments Dr. John Vincent.

The other ciliopathy gene identified in this study - Atxn10 - leads to the condition called nephronophthisis, also associated with kidney and eye problems.

This study moves forward gene research by taking an innovative network approach. Some of the researchers were working on the mapping of a network of potential proteins related to ciliopathies that interact on common pathways, as an approach to identify the disease genes. Another study author, Rachel Giles from University Medical Center (UMC) Utrecht in the Netherlands, comments on this new way of studying networks of proteins and how it could lead to future discoveries of disease genes:
"It's a new language to find genes. The standard methods to find genes in rare genetic diseases in small families are often fruitless. Our method, combining systems biology and biochemistry, has succeeded in this case. It offers families with ''orphan diseases'' and their physicians help to diagnose and understand the natural course of the disease. Moreover, this method could also be used to find genes for more common diseases such as diabetes or obesity."

The aim of the SYSCILIA project is to identify the molecular mechanisms characterising cilium function, and the discrete perturbations associated with dysfunction caused by mutations in inherited ciliopathies, applying a systems biology approach. The project consortium, made up of researchers from 16 research institutions from France, Germany, Ireland, Italy, the Netherlands, the United Kingdom and the United States, aims to generate a comprehensive stream of content-rich quantitative data towards systemic analysis of ciliary function.

Since its launch in June 2010, the SYSCILIA project has already yielded considerable results. Last December, scientists studying dogs discovered a novel gene that triggers primary ciliary dyskinesis (PCD), a rare genetic respiratory disease found in both humans and canines.

The SYSCILIA project runs until 2015.

Explore further: New gene that causes intellectual disability discovered

More information: Sand, L., et al. (2011) Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and Pathways. Cell. DOI: 10.1016/j.cell.2011.04.019

Related Stories

New gene that causes intellectual disability discovered

May 12, 2011
A new study involving Canada's Centre for Addiction and Mental Health (CAMH) has found a gene connected with a type of intellectual disability called Joubert syndrome.

Researchers describe genetic basis of rare human diseases

July 8, 2011
Researchers at the University of California, San Francisco and in Michigan, North Carolina and Spain have discovered how genetic mutations cause a number of rare human diseases, which include Meckel syndrome, Joubert syndrome ...

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.

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. ...

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 ...

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 ...


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.