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Rady launches birth defects project

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A new plan to analyze the DNA of patients with birth defects puts Rady Children’s Hospital among a handful of facilities nationwide doing broad-based, pediatric genetic research.

The goal is to find new treatments and cures for an assortment of conditions — from cleft palate to heart abnormalities — that currently have no known cause.

It’s the first undertaking by the hospital’s new genomics institute, which became possible with a $120 million donation from San Diego philanthropists Ernest and Evelyn Rady.

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In a few months, the institute will start collecting DNA samples from patients whose parents have agreed to participate. The program aims to sequence 200 genomes per year, quickly building a database that could shed new light on which genes and environmental factors cause particular birth defects.

Rady officials launched the project even though the institute is still recruiting its first chief executive officer. But Dr. Donald Kearns, the hospital’s president, said he saw no reason to wait.

The Radys were clear about how their contribution should be used, Kearns recalled.

“His imperative was, ‘Get out there and make kids healthier,’ and that’s what the birth defects initiative is about,” he added.

The Rady Pediatric Genomics and Systems Medicine Institute is part of an emerging wave of research that seeks to determine which variations in the human genome result in disease.

“All of us have differences in our genomes. One of the challenges now is to determine what’s just a common benign variation versus what’s something that is leading to disease susceptibility. The more patients you sequence, the more data is obtained to answer those questions,” said Dr. Cynthia Powell, director of the Medical Genetics Residency Program at the University of North Carolina at Chapel Hill.

Growing endeavor

The field of genomics is booming, in large measure because of breakthroughs in DNA sequencing technology developed by the company Illumina and others in San Diego.

Like most areas of biomedicine, the government, companies and life-science labs are investing much more money on adult genomics. The new institute at Rady Children’s Hospital is among the few facilities in the United States devoted to genetic analysis for children.

In fact, Powell said she is not aware of any other genetic-sequencing effort in the world with such a broad swath of birth-defect patients.

There are a few similar initiatives across the nation, including whole genome sequencing of critically ill newborns at Children’s Mercy Hospital in Kansas City. At St. Jude Children’s Research Hospital in Memphis, Tenn., the Pediatric Cancer Genome Project is sequencing the DNA of 600 cancer patients.

These efforts and others like them represent a turning point for genetic research, Powell said.

“Historically, we’ve dealt with relatively rare diseases,” she explained. “Now we’re trying to unlock the causes of more common conditions.”

When fully formed, the Rady institute intends to examine a range of topics including autism, asthma, cancer and neurological development. High-profile recruitments are underway for many of these disciplines, Kearns said.

“We will have some announcements coming up over the next few months,” he said.

Birth defects

Dr. Christina Chambers, a UC San Diego pediatrics professor, will head the birth-defects project. She has served as principal investigator in many national and international research efforts about environmental exposures during pregnancy. Those include the Vaccines and Medications in Pregnancy Surveillance System, the first to evaluate vaccine safety in pregnant women nationwide.

Kearns said having Chambers right in San Diego made it easier to choose the institute’s inaugural project.

“With Tina on board, it made sense that this was the first one to come out swinging on,” Kearns said.

Chambers said by sequencing many children with the same birth defects, there is a chance to use sophisticated computer analysis of those patients’ genomes and electronic medical records to hone in on new targets for novel drugs.

This approach also might identify which elements of a developing child’s environment are causing defects, she said.

“The particularly exciting area for me is just cracking open the window on an area where we really have never had the resources to do the research in the past,” she added.

Once results begin to materialize, Chambers hopes those early findings will lead to grants from agencies like the National Institutes of Health and other organizations. That funding would build on the Radys’ philanthropic base.

Birth defects affect one in every 33 children born in the United States, according to the U.S. Centers for Disease Control and Prevention.

Each year, about 1,200 newborns in San Diego County have a birth defect, Chambers said. About half of those cases have no known cause.

Scientists already understand the underpinnings of some defects. Down syndrome, for example, is known to occur when a child receives an extra copy of a specific chromosome during initial cell division after the mother’s egg is fertilized.

But the origins of other conditions, especially heart abnormalities that can require multiple surgeries during a child’s early years, remain mysterious.

Parental involvement

Beyond diagnosis, genetic information can help with treatment. For example: By looking at a genome, doctors can tell how certain drugs will be metabolized by that person’s body. Such information can guide physicians in tailoring drug doses to different individuals.

Kearns said genetic information will be available for clinical use through Rady’s existing staff of genetic counselors.

“We’re going to be able to do this for a lot of the kids we see. We won’t be able to do it for everybody yet, but our hope is, eventually, to be able to sequence every kid who comes through here,” he added.

As the region’s only children’s hospital, Rady is in a unique position to conduct the genomics research because it generally performs follow-up care for most children with birth defects in San Diego County.

Kearns said the new program will ask parents to enroll their children through their primary care doctors. The project also will ask for DNA samples from parents to give researchers even more ability to determine how genetic changes are inherited.

At the moment, it is unclear who will own the results of the genetic tests performed by the institute. Kearns said California law on this topic is evolving, and that Rady will have its lawyers make sure the hospital is in full compliance.

“We are going to involve our parents and our patients in a very sophisticated informed consent process so we don’t end up on the wrong side of that issue,” Kearns said.

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