The Genetical Theory of Natural Selection
The Genetical Theory of Natural Selection is a book by Ronald Fisher which combines Mendelian genetics with Charles Darwin's theory of natural selection, with Fisher being the first to argue that "Mendelism therefore validates Darwinism" and stating with regard to mutations that "The vast majority of large mutations are deleterious; small mutations are both far more frequent and more likely to be useful", thus refuting orthogenesis. First published in 1930 by The Clarendon Press, it is one of the most important books of the modern synthesis, and helped define population genetics.
Source: Wikipedia — The Genetical Theory of Natural Selection (CC BY-SA 4.0)