Genetic Roots of Disease: Complexity of Genetic Disorders

Strategic Insights -

Researchers at Penn State have found that the constellation of multiple genetic changes scattered throughout a person's DNA plays a key role in the development of complex disorders, such as autism and developmental delay. This study, published in the journal Cell, highlights the complexity of genetic disorders and how they can manifest differently in individuals with the same genetic marker. The researchers also discovered that the bias implicit in selecting samples for genetic research can mask the complicated and varied nature of genetic disorders.

Key Takeaways:

  • The genetic roots of disease do not always grow into clear-cut, easily diagnosed clinical features, and a single gene does not fully explain the cause for a disease or its clinical features.
  • A person's genetic background, or the constellation of multiple genetic changes scattered throughout their DNA, plays a key role in the development of complex disorders.
  • The relationship between primary and secondary variants differs depending on whether they are ascertained from a pool of mostly healthy individuals or from a pool of individuals included for having similar clinical features, such as autism.
  • Certain types of secondary variants influence risk for specific clinical features, such as expansion in a type of variant called a short tandem repeat, which has a higher risk of developing nervous system features in addition to developmental delay.
  • Individuals from the general population show different patterns of secondary variants and clinical features than kids with developmental delays.
  • Treatment strategies need to consider more than just the primary variant and take a more complete approach that considers each individual person's characteristics or clinical features and their unique set of secondary variants.

Statistics:

  • 442 individuals from 124 families were recruited for the study, all of whom had at least one child with developmental delays and known to have the 16p12.1 deletion.
  • 17 classes of secondary variants were evaluated in the study.
  • Certain types of secondary variants were found to influence risk for specific clinical features, such as expansion of short tandem repeats, which had a higher risk of developing nervous system features in addition to developmental delay.

Sources:

  • Cell (Oct. 7)
  • National Institutes of Health
  • Penn State Huck Institutes of the Life Sciences
  • Oak Ridge Associated Universities
  • National Library of Medicine
  • Fulbright Commission Uruguay-National Agency for Research and Innovation
  • Swiss National Science Foundation
  • National Institute for Health and Care Research-Manchester Biomedical Research Centre.