Genetics of sexual development: a new paradigm.

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Genetics of sexual development: a new paradigm. Abstract Text:

Stan R Blecher,Robert P Erickson,Stan R Blecher,Robert P Erickson,Stan R Blecher,Robert P Erickson,

The classical paradigm of human and mammalian sexual development, largely based on work of Alfred Jost, depicts the genetic factor(s) that determine(s) sex as influencing only the fate of the gonad. A maleness factor produces testes (Primary Sex Determination). These organs secrete hormones which cause male Secondary Sexual Differentiation. 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 Pregonadal Stage. Furthermore, female development is not by default-both male (Y) and female (X) sex-chromosomal primary sex-determining mechanisms probably exist. The human/mammalian male Y-chromosomal sex-determining gene is now known (SRY/Sry), and a candidate for a non-inactivated, X-linked, female determining factor, is under study. However, the proximate gonad-determining genes are probably on autosomes. Pathways between the primary factors and the proximate gonad-determining 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 SRY/Sry. Candidates for proximate testis and ovary-determining factors and for Z also exist. The "default" concept has also been superseded with respect to secondary sexual differentiation.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-chromosomal sex-determining genes influence the development not only of non-gonadal organs of secondary sexual development, but also of organs outside of the reproductive system.

Genetics of sexual development: a new paradigm. Publishing Authors By Initials

SR Blecher,RP Erickson,SR Blecher,RP Erickson,SR Blecher,RP Erickson,

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Genetics of sexual development: a new paradigm. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of medical genetics. Part A

VOLUME: 143

Page Numbers: 3054-68

Journal Abbreviation: Am. J. Med. Genet. A

ISSN: 1552-4833

DAY: 15

MONTH: Dec

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 101235741

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AFFILIATION: Department of Molecular Biology and Genetics (Emeritus), University of Guelph, Guelph, Ontario, Canada.

Country: United States

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MEDLINETA: Am J Med Genet A

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