Gene analysis finds ‘fingerprint’ of defects in heart development

Using a multiple-gene analysis technique, German researchers have gained new insights into specific genetic alterations that lead to congenital heart defects, according to a report in today’s rapid access issue of Circulation: Journal of the American Heart Association. The technique, called microarray analysis, allowed investigators to identify specific patterns of gene expression in the entire human genome associated with common types of congenital heart defects. They sought to demonstrate the feasibility of using gene array analysis to study congenital heart defects. But their findings could represent an early step toward developing effective strategies to improve the quality of life in children and adults with heart defects.
From American Heart Association:Gene analysis finds “fingerprint” of defects in heart development

DALLAS, May 13 ? Using a multiple-gene analysis technique, German researchers have gained new insights into specific genetic alterations that lead to congenital heart defects, according to a report in today’s rapid access issue of Circulation: Journal of the American Heart Association.

The technique, called microarray analysis, allowed investigators to identify specific patterns of gene expression in the entire human genome associated with common types of congenital heart defects. They sought to demonstrate the feasibility of using gene array analysis to study congenital heart defects. But their findings could represent an early step toward developing effective strategies to improve the quality of life in children and adults with heart defects.

“The genetics of congenital heart disease points to the existence of powerful factors that influence disease,” says study principal author Silke Sperling, M.D., leader of the cardiovascular genetics research group at Max-Planck-Institute for Molecular Genetics in Berlin. “Tissue analysis of gene expression provides a measure of genetic regulation and leads to the identification of genes in cardiac development.”

“As genes are potential disease modifiers, they may be one piece of the puzzle determining the severity and type of congenital cardiovascular diseases,” she says. “If we can identify high-risk individuals, we might be able to reduce infant death by altering environmental or maternal factors. In addition, better understanding of the disease process and identification of individuals at risk will provide an opportunity to develop preventive strategies.”

Congenital cardiovascular defects occur when the heart or blood vessels near the heart don’t develop normally before birth. They are the most common birth defects in humans, affecting about eight of every 1,000 births, Sperling says.

The preliminary study is the first large-scale evaluation of gene expression patterns in human tissue samples from people with congenital cardiovascular defects, Sperling says. Previously, knowledge about the genetics of heart defects has come mainly from studies of animals.

One gene causes some heart defects, and experts think most heart defects arise from malfunction of multiple genes, says lead author Bogac Kaynak, Ph.D., a student on the cardiovascular genetics research team.

Microarray analysis involves simultaneous evaluation of a large number of genes. It creates scientific order for complex and varied disease processes. The technique’s emergence has coincided with the mapping of the entire human genome, which is essentially completed.

The researchers applied microarray analysis to 55 heart tissue samples from 40 patients ranging from infants to adults undergoing surgery for various types of heart defects. Those samples were compared with tissue obtained from normal donor hearts being used in heart transplantation procedures.

The analysis showed that specific patterns of gene expression are associated with the common congenital heart defects known as tetralogy of Fallot. Tetralogy of Fallot includes: 1) ventricular septal defect, a hole in the wall that separates the lower chambers of the heart (ventricles), 2) pulmonary stenosis, a narrowing of the opening between the pulmonary artery and the right ventricle, 3) enlargement of the right ventricle and 4) the aorta being in the wrong position.

“Known genes associated with these diseases could be confirmed, but even more important, new genes have been identified, and their association and role in the development and progression of the diseases have to be studied in the future,” Sperling says.

The investigation represents a major step forward in understanding complex disease processes, the researchers note.

“Our findings suggest that the study of malformed human hearts, using powerful techniques like microarrays, opens a new window to understand cardiac adaptation and development,” Sperling says.

The research team plans additional studies to build on the progress begun by the current investigation. Eventually the research might lead to approaches to prevent or treat heart defects. The strategies include manipulating genes to cause cells to develop into heart muscle cells that could be used in transplantation or cell replacement procedures.

Other co-authors are Anja von Heydebreck, Ph.D.; Siegrun Mebus, M.D.; Dominik Seelow, M.Sc.; Steffen Hennig, Ph.D.; Jan Vogel, B.Sc.; Hans-Peter Sperling, M.D.; Reinhard Pregla, M.D.; Vladimir Alexi-Meskishvili, M.D., Ph.D.; Roland Hetzer, M.D.; Peter E. Lange, M.D., Ph.D.; Martin Vingron, Ph.D. and Hans Lehrach, Ph.D.


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