Human Genetics

Diagram showing relationship among the genome, chromosomes, DNA, genes and mutations

By performing whole-genome sequencing, scientists hope to identify the abnormal gene or genes that cause underdevelopment of the left ventricle.

Hypoplastic left heart syndrome (HLHS), researchers believe, can likely be traced to abnormal genes that cause underdevelopment of the left ventricle. But today, the identity of that gene or those genes is poorly understood. Discovering the genetic basis for HLHS is one of four key focus areas within the Todd and Karen Wanek Family Program for HLHS at Mayo Clinic.

Long-term objectives

Related to HLHS genetics, Mayo investigators over the long term aim to:

  • Identify the molecular pathways for left heart development that are disrupted in HLHS
  • Develop a genetic testing platform for HLHS and define its role in clinical practice
  • Determine the impact of HLHS-associated mutations on the viability and therapeutic efficacy of patient-derived cardiac myocytes engineered from induced pluripotent stem cells

Investigative strategy

To accomplish these objectives, the human genetics team is:

  • Establishing family histories and populating a HLHS biorepository. Researchers are identifying and recruiting people with HLHS (and their relatives); from these people, they're obtaining detailed family histories and constructing multigenerational pedigrees. They're also procuring blood samples to gather genomic DNA and plasma, which are kept in a secure repository, called a biorepository, for ongoing use in HLHS research.
  • Detecting chromosomal abnormalities and genetic mutations. Using array comparative genomic hybridization (aCGH), a microarray-based analysis method, researchers are trying to detect aneuploidy — gains or losses in chromosomal material — in people with HLHS. Investigators are also utilizing comprehensive whole-genome sequencing and bioinformatics analyses in the search for HLHS-related genetic mutations.
  • Determining mode of inheritance. In conjunction with the imaging and outcome component, researchers are working to determine the manner in which HLHS-associated aneuploidy and mutations are inherited within families, as well as genotype-phenotype correlations.
  • Correlating genetic findings. As researchers home in on the genetic underpinnings of HLHS, they'll work to correlate these findings using transcriptome and proteome profiling of cardiac myocytes derived from people with HLHS.


If you have questions about research within the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome or would like to learn more about research participation, please email us at