Featured Research

from universities, journals, and other organizations

Insights into genetics of cleft lip

Date:
May 26, 2014
Source:
European Molecular Biology Laboratory (EMBL)
Summary:
A specific stretch of DNA controls far-off genes to influence the formation of the face, researchers have found. The new study, outlining how this is done, helps understand the genetic causes of cleft lip and cleft palate, which are among the most common congenital malformations in humans.

Lack of a particular stretch of DNA can lead to cleft lip (bottom) in mice.
Credit: © EMBL/V.V.Uslu

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, have identified how a specific stretch of DNA controls far-off genes to influence the formation of the face. The study, published today in Nature Genetics, helps understand the genetic causes of cleft lip and cleft palate, which are among the most common congenital malformations in humans.

Related Articles


"This genomic region ultimately controls genes which determine how to build a face and genes which produce the basic materials needed to execute this plan," says Franηois Spitz from EMBL, who led the work. "We think that this dual action explains why this region is linked to susceptibility to cleft lip or palate in humans."

Previous studies had shown that variations in a large stretch of DNA are more frequent in people with cleft lip or cleft palate. But there are no genes in or around this DNA stretch, so it was unclear what its role might be. To answer this question, Spitz and colleagues genetically engineered mice to lack that stretch of DNA, as the mouse and human versions are very similar, and are therefore likely to have the same role in both species. They found that these genetically engineered mice had slight changes to the face -- such as a shorter snout -- and a few had cleft lips. The scientists also used this mouse model to look at what happened during embryonic development to lead to those changes.

"We found that this stretch of DNA contains regulatory elements that control the activity of a gene called Myc, which sits far away on the same chromosome," Spitz explains, "and it exerts that control specifically in the cells that will form the upper lip."

The researchers discovered that, in the face of mouse embryos that lack this stretch of DNA, Myc becomes largely inactive. This in turn affects two groups of genes: genes directly involved in building the face, and genes that make ribosomes, the cell's protein-producing factories. The latter effect could make the developing upper lip more sensitive to other genetic conditions and to environmental factors -- like smoking or drinking during pregnancy -- that can influence cell growth. This is because making the face in general, and the upper lip in particular, are very complex processes, requiring different groups of cells in the embryo to grow and fuse with each other at the right time. If the cells involved have their protein production impaired -- due to reduced Myc activity -- any additional burden could disrupt that growth, increasing the likelihood of a malformation like cleft palate. This increased susceptibility to a wide range of factors -- both genetic and environmental -- could the link between variations in this stretch of DNA and the incidence of cleft lip.

The EMBL scientists would now like to use their genetically engineered mice to untangle the interplay between genetic and environmental factors. They would also like to investigate how this stretch of DNA can control Myc across such a long distance, and determine the exact role of the genetic variants found in humans.


Story Source:

The above story is based on materials provided by European Molecular Biology Laboratory (EMBL). Note: Materials may be edited for content and length.


Journal Reference:

  1. Veli Vural Uslu, Massimo Petretich, Sandra Ruf, Katja Langenfeld, Nuno A Fonseca, John C Marioni, Franηois Spitz. Long-range enhancers regulating Myc expression are required for normal facial morphogenesis. Nature Genetics, 2014; DOI: 10.1038/ng.2971

Cite This Page:

European Molecular Biology Laboratory (EMBL). "Insights into genetics of cleft lip." ScienceDaily. ScienceDaily, 26 May 2014. <www.sciencedaily.com/releases/2014/05/140526101700.htm>.
European Molecular Biology Laboratory (EMBL). (2014, May 26). Insights into genetics of cleft lip. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2014/05/140526101700.htm
European Molecular Biology Laboratory (EMBL). "Insights into genetics of cleft lip." ScienceDaily. www.sciencedaily.com/releases/2014/05/140526101700.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) — The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) — Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) — Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins