Shedding new light on genetic dark matter 英文参考文献.docVIP

Melhem and Devlin Genome Medicine 2010,2:79 /content/2/10/79 CO MMENTA RY Shedding new light on genetic dark matter Nadine Melhem and Bernie Devlin* Narrow-sense heritability involves only the additive Abstract e?ects of genes. Broad-sense heritability involves both additive and non-additive e?ects. e di?erence between the two makes a di?erence when hunting for dark matter. If genetic variation were all to act additively, the best predictor of an o?spring’s trait value would be the average of his/her parents’ values. Human height is an excellent example, after adjusting for gender. Hunting for dark matter for a trait such as human height will be more straightforward than for a disease such as schizophrenia, for which the evidence for substantial gene-gene inter- action is compelling [4]. Yet when researchers refer to heritability of human height, they implicitly mean narrow-sense heritability; for schizophrenia, it is heritability in a much broader sense. Discoveries from genome-wide association studies have contributed to our knowledge of the genetic etiology of many complex diseases. However, these account for only a small fraction of each disease’s heritability. Here, we comment on approaches currently available to uncover more of the genetic‘dark matter,’including an approach introduced recently by Naukkarinen and colleagues. These authors propose a method for distinguishing between gene expression driven by genetic variation and that driven by non- genetic factors. This dichotomy allows investigators to focus statistical tests and further molecular analyses on a smaller set of genes, thereby discovering new genetic variation aecting risk for disease. We need more methods like this one if we are to shed a powerful light on dark matter. By enhancing our understanding of molecular genetic etiology, such methods will help us to understand disease processes bett