Genetic Investigations into HLHS- Part 2

In follow up to Genetic Investigations into HLHS- part 1, we sat down with Dr. Timothy Olson, a pediatric cardiologist with a research focus in cardiovascular genetics at Mayo Clinc in Rochester to discuss whole genome sequencing, the second research strategy he uses to study HLHS genetics. If we think about the human genome as a book, whole genome sequencing would look at every single letter in the book.

In part 1, we talked about aCGH, which detects larger pieces of DNA - or, using book example, several pages or even a whole chapter of the book - that are either missing from the genetic blue print or extra pieces of genetic material. Having too little or too much of a series of genes can cause problems.

Genetics research is only possible through the participation of families, so this research begins with recruiting individuals with HLHS and their family members and collecting a sample - typically a blood sample - from which DNA is extracted.

"We study the DNA, and we use a very new technique that enables us to survey the entire genome, which is called Next Generation Sequencing or Whole Genome Sequencing," explains Dr. Olson. "This allows us to identify point mutations, genetic flaws in essence, in a single letter of the genetic code."

The objective is to try and pinpoint the defect or flaw within the genetic code that leads to the underdevelopment of the left side of the heart in HLHS. "Once we've done that, we can begin to understand some of the mechanisms and biological pathways that are important in normal development of the heart and which, when disrupted, lead to HLHS," says Dr. Olson.

The ultimate goal of the Todd and Karen Wanek Program for Hypoplastic Left Heart Syndrome is to use a cell-based therapy to maintain the health of the right ventricle. Dr. Olson says, "If we can understand the genetic underpinnings, it may help us customize the cells that we use for therapy. In some cases, because we are using cells from a patient's own body, we may have to think about correcting the genetic defect that exists within those cells before we deliver those cells back to the patient to be used therapeutically."

To learn more about the genetics research going on the program, read more on the genetics page of the program's website.