Edward Lammer, MD (CHORI Scientist): I am Ed Lammer and I am a pediatrician and medical geneticist here at Childrens Hospital in Oakland. We are using a technique that is called a Comparative Genomic Hybridization and that technique is a micro array type of technique and we use the technique in such a way that we compare the chromosomes of a healthy individual to children who were born with congenital heart defects. David Iovannisci, PhD (CHORI Assistant Scientist): So we mix together 2 DNAs- a reference DNA and a test DNA and they are labeled with 2 different colors and we carefully label the DNAs as equally as we can and then we quannotate the DNAs so that we have equal amounts of DNAs that we are mixing together and then we hybridize those DNAs to a slide that has probe molecules that covers the entire human genome and if there is equal hybridization between the 2 different colors the hybridization signal will show up as yellow and if there is a deletion, then the hybridization signal will show up as red. So we are looking at deletions along chromosomes of the tested individual.Kazutoyo Osoegawa, PhD (CHORI Assistant Scientist): Some genes, which is critical for the development of human may be missing. So when we found this deletion, we are suspecting that this deletion may affect the cause of congenital heart defects. Ed Lammer: This technique we think, will help jumpstart searches because it is a faster way to hone in on likely good candidate regions where genes might lie that are important for congenital heart disease. If you aggregate together all of the children born with different types of congenital heart disease, that group of kids represents the most common grouping of birth defects that we see. So it is clear the congenital heart disease is a great public health burden for the country in terms of the number of children that are affected and the amount of public health dollars that must go toward surgery and care in the hospital and as outpatients for those children.Kazutoyo Osoegawa: So, I am so glad that I was able to come back to the Institute to keep on the research that I have been heavily involved and I am glad that I was able to continue on the research that I have been very interested in for the last several years. David Iovannisci: The stimulus has really helped me keep my job. I have trained as a geneticist for about 30 years and to not be able to make use of that knowledge and training that I have had to contribute to research, really would be a personal loss to myself, and I think, you know, a loss to research
Edward Lammer, M.D. Principal Investigator, Children's Hospital and Research Center at Oakland, Oakland, California Chromosomal Microdeletions Causing Heart Defects Administered by the NHLBI Division of Cardiovascular Sciences, Heart Development and Structural Diseases Branch FY 2009 Recovery Act Funding: $668,140
Research Focus:Congenital heart defects are the most common type of birth defect, affecting eight out of every 1,000 newborns. The frequency of recurrences in the same families strongly suggests there are genetic contributions.
Edward Lammer, M.D., and his team are searching for chromosomal abnormalities among 500 California infants who were born between 1999 and 2004 with conotruncal defects that cause improper blood circulation. These life-threatening birth defects require costly medical interventions throughout life. The 500 infants were enrolled by their parents in a recently completed population-based case-control study of infants with conotruncal defects-the largest of its kind and the result of a collaboration between Children's Hospital Research Institute (CHORI) and March of Dimes-California Research Division.
'Without knowing the genetic and environmental contributors, we cannot develop prevention plans for these heart defects," said Dr. Lammer. 'This includes more informed reproductive planning for parents and their children, as well as better clinical care for children born with conotruncal defects. Identifying genes that cause heart defects may help us better predict later complications such as arrhythmias that may be characteristic of some genes.
Dr. Lammer's team will employ a high-resolution, genome-wide screening technique, array comparative genomic hybridization (array-CGH), to detect submicroscopic chromosomal imbalances. This investigation, according to Dr. Lammer, complements past studies sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of genetic and environmental contributions to causes and outcomes of congenital heart defects.
'I'm hoping we can make quite a bit of progress in two years," said Dr. Lammer. "It helps a lot that we already have DNA samples from a large population of California children born with heart defects. So we can move right from the DNA samples to the searches for the chromosomal abnormalities. Our project was exactly what the president wanted: shovel-ready."
Economic Impact: 'Without the support of the NHLBI's Recovery Act grant, our efforts in this area of research would have been severely pared back," said Dr. Lammer.
According to Dr. Lammer, the NHLBI Recovery Act grant helped create jobs for three scientists:
Kazutoyo Osoegawa, Ph.D., whose staff research position in another lab at CHORI had been eliminated at the end of 2008. Much of the preliminary data used to apply for the NHLBI/Recovery Act grant was developed from a study on cleft lip palate that was published in 2007 by Dr. Osoegawa.
David Iovannisci, Ph.D., who had begun searching for jobs outside of CHORI when he learned that more than half of his salary support would be cut on July 1, 2009.
A lab technician who had been expecting to be laid off on July 1.
A Scientist's Inspirations: 'My 10th grade biology teacher gave me several books about evolution and Darwin, including The Voyage of the Beagle," said Dr. Lammer. 'If every student read that story of Darwin's voyage, there might be more passion for the life sciences.
'If I had to name one scientific 'hero,' it would be Dr. Rita Levi-Montalcini," added Dr. Lammer. "She was a biology professor at Washington University when I was an undergrad, and I opted to take a verbal final exam with her rather than the written exam. That was quite an experience. She was later awarded a 1986 Nobel Prize in Physiology or Medicine for her work on the identification of nerve growth factor. Her 1988 autobiography, 'In Praise of Imperfection," is a marvel. During World War II, because she was a Jew, she was eventually banned from the Turin lab where she was a graduate student. She continued many of her experiments at her apartment, even incubating chick eggs under her bed."
A Scientist's Hope: "I hope that the work that we do makes a difference in children's lives," said Dr. Lammer.