Genetics, Vol. 179, 1741-1756, August 2008, Copyright © 2008
doi:10.1534/genetics.108.094128

Tilting at Quixotic Trait Loci (QTL): An Evolutionary Perspective on Genetic Causation

Kenneth M. Weiss1

Department of Anthropology and Integrated Biosciences Genetics Program, Pennsylvania State University, University Park, Pennsylvania 16802

1 Address for correspondence: Department of Anthropology, Pennsylvania State University, 409 Carpenter Bldg., University Park, PA 16802.
E-mail: kenweiss{at}psu.edu

Recent years have seen great advances in generating and analyzing data to identify the genetic architecture of biological traits. Human disease has understandably received intense research focus, and the genes responsible for most Mendelian diseases have successfully been identified. However, the same advances have shown a consistent if less satisfying pattern, in which complex traits are affected by variation in large numbers of genes, most of which have individually minor or statistically elusive effects, leaving the bulk of genetic etiology unaccounted for. This pattern applies to diverse and unrelated traits, not just disease, in basically all species, and is consistent with evolutionary expectations, raising challenging questions about the best way to approach and understand biological complexity.