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These organs secrete hormones which cause male <jats:italic>Secondary Sexual Differentiation<\/jats:italic>. In absence of the maleness factor, by default the gonad becomes an ovary, and the absence of testicular hormones leads to female secondary differentiation. In this article a new paradigm is proposed, to accommodate recent findings. Sexual dimorphism precedes gonadal development, in a <jats:italic>Pregonadal Stage<\/jats:italic>. Furthermore, female development is not by default\u2014both male (Y) and female (X) sex\u2010chromosomal primary sex\u2010determining mechanisms probably exist. The human\/mammalian male Y\u2010chromosomal sex\u2010determining gene is now known (<jats:italic>SRY<\/jats:italic>\/<jats:italic>Sry<\/jats:italic>), and a candidate for a non\u2010inactivated, X\u2010linked, female determining factor, is under study. However, the proximate gonad\u2010determining genes are probably on autosomes. Pathways between the primary factors and the proximate gonad\u2010determining genes are indirect and complex. A hypothetical gene Z has been proposed, that inhibits the testis determiner and is itself the target of suppression by <jats:italic>SRY<\/jats:italic>\/<jats:italic>Sry<\/jats:italic>. Candidates for proximate testis and ovary\u2010determining factors and for <jats:italic>Z<\/jats:italic> also exist. The \u201cdefault\u201d concept has also been superseded with respect to secondary sexual differentiation. Absence of testicular hormones does not produce a normal female phenotype; ovarian genes and hormones are necessary. Finally, sex\u2010chromosomal sex\u2010determining genes influence the development not only of non\u2010gonadal organs of secondary sexual development, but also of organs outside of the reproductive system. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32037","type":"journal-article","created":{"date-parts":[[2007,11,14]],"date-time":"2007-11-14T02:16:47Z","timestamp":1195006607000},"page":"3054-3068","source":"Crossref","is-referenced-by-count":55,"title":["Genetics of sexual development: A new paradigm"],"prefix":"10.1002","volume":"143A","author":[{"given":"Stan R.","family":"Blecher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert 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