Mongolism and sex: a common problem of cell proliferation?

It is now evident that variations in chromosome constitution may have a profound effect on physical and mental development, both normal and pathological. Mongolism is the best known example of a severe congenital abnormality caused by the presence of an additional chromosome; while a difference in the sex chromosome constitution-XY in the male and XX in the female-produces the most far-reaching normal variation in human beings and other animal species. In spite of the spectacular progress in our knowledge of human chromosomes during the past 15 years, there is as yet no working hypothesis relating cause and effect; in other words, we need an answer to the question: 'By what mechanism do different chromosome constitutions result in different end products of development?'