Tag: DNA

Aging leaves a chemical signature on DNA, statistical models known as epigenetic clocks estimating a person’s age with relatively high accuracy. However, new research by assistant professor and member of the Institute of Human Genetics Dr. Shyamalika Gopalan and collaborators from France show many of these clocks do not tell time well for some populations.

“None of these clocks are perfect. None of them are going to be,” Gopalan said. “But for some people, they can be way off because of genetic variation.”

 Most of the research and the clocks were built around European ancestry. The recently published work, “Common DNA sequence variation influences epigenetic aging in African populations,” found that these clocks show differences in accuracy when applied to different populations from around the world.

“Human genetics is very biased toward Western European ancestry samples. It is data from those populations that is the most widely available and mostly widely used,” Gopalan said. “African populations have more genetic diversity than the majority of populations that we tend to study in human genetics. Our hypothesis was that genetic variation can bias these predictive models in ways that haven’t been accounted for,” she said.  “It essentially means that the same level of DNA methylation can translate to a very different age prediction depending on your genotype.”

The researchers instead studied clocks to the African populations, which mostly showed significantly higher errors compared to publicly available DNA data from European and Hispanic/Latino individuals. When the researchers found this difference, they were able to reduce the error in the African cohorts while maintaining accuracy in the European and Hispanic/Latino samples.

“This study shows that we can’t necessarily take a model that was developed in one population and just apply it to another population and expect it to produce similar results,” Gopalan said. “Ideally, we would have better representation of global populations in our datasets so that we could build and train epigenetic clocks that perform better on everyone.”

Professor Dr. Alex Feltus is part of a new collaborative research study that found some genetic traits modern humans inherited from Neanderthals may increase a person’s susceptibility to autism. The study suggests long-term effects of ancient human hybridization on brain organization and function and could possibly lead to earlier diagnosis.

“This is the first evidence that I am aware of actually showing that Neanderthal DNA is associated with autism,” said Dr. Feltus.

In this study, the researchers used data from publicly available data bases: Simons Foundation Powering Autism Research (SPARK). They found specific Neanderthal genetic markers were enriched in people with autism compared to ethnically-matched control groups.

However, this does not mean that everyone who has these Neanderthal-derived variations will develop autism. The hypothesis of the study is instead, that Neanderthals gave us some of the gene tweaks that give a higher susceptibility for autism.

“Autism is a complex trait. It is controlled by many, many genes. A big part of what we do in my lab is try to understand the level of complexity,” said Dr. Feltus. “Of the 60,000 genes in the human genome, how many genes are at play when you’re developing autism or cancer or any other complex trait? We embrace complexity. We don’t try to erase complexity.”

Detailed findings were published in the journal Nature: Molecular Psychiatry in an article titled “Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings.”