QTL Mapping

Quantitative trait locus (QTL) mapping is a statistical method for identifying chromosomal regions that contain genes influencing a continuously varying phenotype. By crossing lines that differ in the trait of interest and genotyping the offspring, researchers correlate phenotypic variation with genetic marker variation to locate regions of the genome associated with the trait.

The method was developed in the 1980s and revolutionized the study of complex traits in plants, animals, and humans. Where classical genetics could map single-gene Mendelian traits, QTL mapping provided a way to find the many loci of small effect that underlie quantitative traits.

QTL mapping has limitations that are often understated. It detects associations, not causation. It assumes simple genetic architectures. And it has low power for traits influenced by many loci of very small effect — precisely the architecture that genome-wide association studies later revealed as typical for human complex traits. The gap between QTL peaks and causal variants remains wide, and the jump from chromosomal region to molecular mechanism requires additional experimental work that QTL mapping does not provide.

QTL mapping was sold as the bridge between quantitative genetics and molecular biology. In practice, it is a bridge to more bridges — each narrower and more rickety than the last.