Revolutionizing the Research of Birth Defects
CHORI Scientists Utilize Cross-disciplinary Approach
to Pioneer Novel Application of Array Comparative Genomic Hybridization to Birth Defects Analysis
Cleft lip and cleft palate are orofacial birth defects that affect approximately 1 to 2 per 1,000 births. As they are fairly common, studies have long been underway to elucidate the genes that might be responsible for causing cleft lip and cleft palate. Such studies, however, have utilized only two kinds of genetic analysis, linkage analysis and association studies, both of which have some limitations.
"Not only do you need a large number of samples for the analysis to be significant, but even if you can narrow kind of narrow down where a candidate gene might be located, it's very difficult to pinpoint," explains Dr. Osoegawa. "Linkage analysis for example, might identify a potential candidate gene region as large as 10 megabases.
Array-CGH, however, surveys every chromosome, genome-wide, for microdeletions and/or duplications that would never be seen with standard chromosomal studies.
In simple terms, the technique labels test samples, taken from affected DNA, and reference samples, representing unaffected DNA, in two different colors.
"In total we analyzed about 200 DNA samples and we were able to find 2 or 3 candidate genes," says Dr. Osoegawa. "We feel that's pretty effective in terms of narrowing down and identifying candidate gene locis compared to the other methods."
Given how successful the array-CGH has proven, CHORI investigators are hopeful that the publication proves a harbinger of many more birth defects studies applying the novel technology.
"The results of this study are really quite exciting, and should spur lots of people on to apply this technique to kids with common birth defects, or even isolated birth defects," says Dr. Lammer. "At least that's the message we're trying to give."
In the mean time, the group of researchers hopes to expand their investigations to identify more candidate genomes for cleft lip and cleft palate, as well as putting the array-CGH to potential use in the analysis of other diseases.Back
Monday, May 16, 2011 11:33 PM