U. researchers develop technique to probe ‘missing heritability’

A new University study recently published in Nature has shown that extensive genetic mapping can be used to trace the genetic origins of even the smallest trait variations, providing support for 20th-century scientific arguments that privilege nature over nurture.

The study was conducted by Joshua Bloom, a graduate student in the molecular biology department who developed the project for his Ph.D., and ecology and evolutionary biology professor Leonid Kruglyak ’87.

Bloom was unavailable to comment for this article.

Thuy-Lan Vo Lite ’12, who worked on the project for her senior thesis, said she enjoyed participating in the investigation of the “missing heritability,” a mystery that has existed in genetics since the 1920s.

“In humans there’s this problem where even in traits that we know are heritable, we can’t really find all the genetic components to fully explain that heritability,” Lite said. “But in this project, we are able to take a heritable trait like drug response and find all of the genetic components responsible for the phenotype. And we can predict the phenotype very accurately from the genotype.”

Lite said the new genetic mapping technique has given new evidence for the genetic “nature” of an organism to dictate every inherited trait. While the previous technique for tracking genetic features in humans had allowed scientists to understand heritability, the majority of variation in inherited traits has so far been inexplicable. Variations in inherited traits like height and genetic disease could not be attributed to particular genes. By default, they had been attributed to an organism’s environment, the “nurture” of “nature versus nurture.”

However, by changing their approach, Bloom and his research team determined that this so-called “missing heritability” can be traced through genes. For many inherited traits, variation in what is expressed can be explained by each trait’s extended network of genes, rather than individual areas of the genome, according to Kruglyak.

Bloom’s technique involved studying enormous generations of yeast that inherited their ancestors’ genes in ways that the scientists could measure. By crossing two different strains of yeast — one developed in the lab and one from a vineyard — Bloom used simulations and breeding techniques to model and grow extended families.

By using yeast, a very simple organism with a linear genome, Bloom was able to develop a system that simultaneously introduced variety in the gene pool and allowed individual traits to be measured over large scales, Kruglyak said. In this way, Bloom was able to monitor specific variations and account for almost all of the yeast’s genetic features.

According to Kruglyak, while the results are not yet directly applicable to humans, they offer the exciting possibility of understanding every genetic trait with an extensive and large-scale operation.

“We could have done a study of this scale and found that most of the heritability was missing,” he said. “And so it was pretty cool to see that, at least in the simplified case, we could actually say that for all of these different traits we really can find 80-90 percent of the heritable traits that we expect to be there, due to these specific well-defined regions of the genome that we can pin down.”

Kruglyak said extending this research to humans could introduce complications because there is no way to monitor human genetic heritage on a similar scale. But he said he found the results exciting as a confirmed case in which biologists’ understanding of genetics was significantly improved with a simpler model.