VAI takes out-of-box approach in neonatal blood study effort

December 22, 2008
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Van Andel Institute researchers have distinguished themselves once again, this time as the first to apply RNA technology to measure the genes in samples of neonatal blood. VAI researchers used the technology on a random sample of newborn “blood spots” collected from 1998 to 2004 and were able to detect an average of 3,480 genes in each sample.

James Resau, Ph.D., VAI distinguished scientific investigator, deputy director of special programs and director of VAI’s Division of Quantitative Sciences, said the belief has always been that there wouldn’t be enough RNA on infant blood spot cards for research purposes: For years the dogma has been that RNA is very rapidly degraded and that it can’t exist for a long period of time on a dry card filed in a storage cabinet.

“I said, ‘Well, they’re probably right but we really should test, because we have better techniques now,’” Resau explained. “Just because someone says this or that is the case doesn’t mean you shouldn’t investigate it.”

There are 20,000 genes, plus or minus, in the human genome, and VAI researches were able to routinely get 3,000 to 4,000 reproducible spots, or gene signatures, in their pilot study.

“Anytime you have 3,000 or 4,000 ways to discriminate one sample from another, your ability to discriminate with accuracy is much improved,” Resau explained. He thinks neonatal blood spots are an underutilized resource in disease research.

“I don’t mean to imply that neonatal blood spots have been badly utilized, it’s just that they haven’t been used for gene expression and genomic work because of the presumption that it wouldn’t work, and our research shows it should work, so now I think people will begin to test them.”

Blood spots are obtained at the time of birth: The attending physician pricks the heel of a newborn and dabs a few tiny drops of blood on a filter paper. The blood spots are screened by the state department of health for metabolic diseases, which helps in the early diagnosis of disease. They’re then archived for 21 years or more, depending on state law. Michigan has had a law in effect since 1986 that requires the Michigan Department of Community Health to store neonatal blood spots for 21.5 years. Michigan law also encourages the use of archived blood spots for medical research.

Resau said many of the blood spots are stored in room temperature conditions so they are basically dried blood on filter paper. Even so, he said, VAI researchers were able to glean good RNA test results from samples that had been in storage for as long as nine years. The VAI used 85 blood spot cards from the department of health and looked at 12 spots from four different arrays.

Diseases that show up early in an individual’s life — such as the kidney cancer known as Wilms, pediatric brain cancer, cerebral palsy, and some of the leukemias and lymphomas — are more likely to have a genetic component, whereas diseases that occur later in life are more likely to have an environmental component, such as smoking, poor diet and lack of exercise, Resau observed. 

“Presumably, those childhood diseases would have a signature at birth because they arrive within the first year after birth. Presumably, you could screen for that and do interventions at the earliest possible moment,” he said. “The inference of this study is that states can now do genetic screening in addition to metabolic screening.”

By teaming with state health departments and utilizing existing blood spot archives, Resau hopes researchers will be able to improve their understanding of diseases that aren’t immediately apparent at birth but have roots in the perinatal period.

“Measuring the relative abundance of thousands of expressed genes from universally collected neonatal blood spots may open new avenues of research into perinatal markers and determinants of disease development,” he explained.

Researchers in VAI’s Laboratories of Microarray Technology and Molecular Epidemiology and lead author of the study, Peterson T. Haak, were assisted in the study by Nigel Paneth, M.D., and his colleagues at Michigan State University’s College of Human Medicine, College of Osteopathic Medicine and its Department of Physiology. Paneth secured all the approvals through MSU and worked directly with people at the Michigan Department of Public Health to get the blood spot samples, Resau noted.

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