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ARTICLE |

The Y Chromosome and Primary Sexual Differentiation FREE

Renée Bernstein, MB, BCh
[+] Author Affiliations

Reprint requests to Department of Human Genetics, University of the Witwatersrand, PO Box 1038, Johannesburg 2000, South Africa (Dr Bernstein).


JAMA. 1981;245(19):1953-1956. doi:10.1001/jama.1981.03310440049029
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The mammalian Y chromosome plays a dominant role in initiating fetal testicular differentiation. Testicular differentiating genes on the Y chromosome can be serologically detected as H-Y antigen. The correlation of numerical and structural abnormalities of the X and Y chromosomes, combined with H-Y antigen reactivity, gonadal histology, and phenotype, has contributed to mapping the locus of these genes on the Y chromosome and has elucidated some of the mechanisms responsible for anomalous primary sexual differentiation. The causes for failure of gonadal differentiation despite the presence of a Y chromosome or for testicular differentiation in the absence of a detectable Y are discussed. Evidence is presented for genes on the X chromosome that regulate the activity of testicular differentiating genes on the Y chromosome.

(JAMA 1981;245:1953-1956)

REFERENCES

Ford CE:  Cytogenetics and sex determination in man and mammals . J Biosoc Sci 1970;; 2( (suppl) ):7-30.
Jost A:  A new look at the mechanisms controlling sex differentiation in mammals . Johns Hopkins Med J 1972;;130:38-53.
Wachtel SS, Ohno S:  The immunogenetics of sexual development . Prog Med Genet 1979;; 3:109-142.
Wilson JD, Goldstein JL:  Classification of hereditary disorders of sexual development , in Bergsma D (ed): Genetic Forms of Hypogonadism . Birth defects original article series XI. New York, Stratton Intercontinental Medical Book Corp, 1975;, pp 1-16.
Wachtel SS:  The genetics of intersexuality: Clinical and theoretical perspectives . Obstet Gynecol 1979;;54:671-685.
Simpson JL:  Klinefelter syndrome , in Disorders of Sexual Differentiation: Etiology and Clinical Delineation . New York, Academic Press Inc, 1976;, pp 303-322.
Wachtel SS, Koo GC, Breg WR, et al:  Expression of H-Y antigen in human males with two Y-chromosomes . N Engl J Med 1975;; 293:1070-1072.
Cattanach BM: ' XO mice .' Genet Res 1962;; 3:487-490.
Short RV:  Sex determination and differentiation of the mammalian gonad . Int J Androl 1978;;2( (suppl) ):21-28.
Bernstein R, Koo GC, Wachtel SS:  Abnormality of the X chromosome in human 46,XY female siblings with dysgenetic ovaries . Science 1980;;207:768-769.
Bielert C, Bernstein R, Simon GB, et al:  XY gonadal dysgenesis in a chacma baboon . (Papio ursinus). Int J Primatol 1980;;1:3-13.
Koo GC, Wachtel SS, Krupen-Brown K, et al:  Mapping the locus of the H-Y gene on the human Y-chromosome . Science 1977;;198:940-942.
Rary JM, Cummings DK, Jones HW Jr, et al:  Assignment of the H-Y antigen gene to the short arm of chromosome Y . J Hered 1979;; 70:78-80.
Khodr GS, Gary DC, Teng C, et al:  Y-autosome translocation, gonadal dysgenesis and gonadoblastoma . Am J Dis Child 1979;;133:277-282.
German J, Simpson JL, Chaganti RSK, et al:  Genetically determined sex-reversal in 46,XY humans . Science 1978;;202:53-56.
Fredga K, Gropp A, Winking H, et al:  Fertile XX and XY type females in the wood lemming Myopus schisticolor . Nature 1976;; 261:225-227.
Wachtel SS, Koo GC, Ohno S, et al:  H-Y antigen and the origin of XY female wood lemmings (Myopus schisticolor) . Nature 1976;; 264:638-639.
Herbst EW, Fredga K, Frank F, et al:  Cytological identification of two X-chromosome types in the wood lemming (Myopus schisticolor) . Chromosoma 1978;;69:185-191.
Ghosh SN, Shah PN, Gharpure HM:  Absence of H-Y antigen in XY females with dysgenetic gonads . Nature 1978;;276:180-181.
Wachtel SS, Koo GC, de la Chapelle A, et al:  H-Y antigen in 46,XY gonadal dysgenesis . Hum Genet 1980;;54:25-30.
Ohno S:  The original function of MHC antigens as the general plasma membrane anchorage site of organogenesis-directing proteins . Immunol Rev 1977;;33:59-69.
Muller U, Aschmoneit I, Zenzes MT, et al:  Binding studies of H-Y antigen in rat tissues: Indications for a gonad-specific receptor . Hum Genet 1978;;43:151-157.
Hall BD, Spranger JW:  Campomelic dysplasia: Further elucidation of a distinct entity . Am J Dis Child 1980;;134:285-289.
De la Chapelle A, Hortling H, Niemi M, et al:  XX sex chromosomes in a human male: First case . Acta Med Scand 1964;;412( (suppl) ):25-38.
Miro R, Caballin MR, Marsini S, et al:  Mosaicism in XX males . Hum Genet 1978;;45:103-106.
Ferguson-Smith MA:  X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome . Lancet 1966;;2:475-475.
Pearson PL, Bobrow M:  Definitive evidence for the short arm of the Y chromosome associating with the X chromosome during meiosis in the human male . Nature 1970;;226:959-961.
Race RR, Sanger R:  Xg and sex chromosome aneuploidy , in Blood Groups in Man , ed 6. Oxford, England, Blackwell Scientific Publications, 1975;, pp 619-635.
Bernstein R, Wagner J, Isdale J, et al:  X-Y translocation in a retarded phenotypic male: Clinical, cytogenetic, biochemical and serogenetic studies . J Med Genet 1978;;15:466-474.
Bernstein R, Pinto MR, Almeida H, et al:  X-Y translocation in an adolescent mentally normal phenotypic male with features of hypogonadism . J Med Genet 1980;;17:437-443.
Evans HJ, Buckton KE, Spowart G, et al:  Heteromorphic X chromosomes in 46,XX males: Evidence for the involvement of X-Y interchange . Hum Genet 1979;;49:11-31.
Cattanach BM, Pollard CE, Hawkes SG:  Sex reversed mice: XX and XO males . Cytogenetics 1971;;10:318-337.
Basrur P-K, Kanagawa H:  Anatomic and cytogenetic studies on 19 hornless goats with sexual disorders . Ann Genet Paris 1969;;1:349-378.
De la Chapelle A, Schröder J, Murros J, et al:  Two XX males in one family and additional observations bearing on the etiology of XX males . Clin Genet 1977;;11:91-106.
Wachtel SS, Koo GC, Breg WR, et al:  Serologic detection of a Y-linked gene in XX males and XX true hermaphrodites . N Engl J Med 1976;;295:750-754.
Bennett D, Mathieson BJ, Scheid M, et al:  Serological evidence for H-Y antigen in Sxr, XX sex-reversed phenotypic males . Nature 1977;; 265:255-257.
Wachtel SS, Basrur P, Koo GC:  Recessive male-determining genes . Cell 1978;;15:279-281.
Van Niekerk WA:  Cytogenetic findings , in True Hermaphroditism: Clinical, Morphologic and Cytogenetic Aspects . Hagerstown, Md, Harper & Row Publishers Inc, 1974;, pp 129-141.
Selden JR, Wachtel SS, Koo GC, et al:  Genetic basis of XX male syndrome and XX true hermaphroditism: Evidence in the dog . Science 1978;;201:644-646.
Winters SJ, Wachtel SS, White BJ, et al:  H-Y antigen mosaicism in the gonad of a 46,XX true hermaphrodite . N Engl J Med 1979;;300:745-749.

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Ford CE:  Cytogenetics and sex determination in man and mammals . J Biosoc Sci 1970;; 2( (suppl) ):7-30.
Jost A:  A new look at the mechanisms controlling sex differentiation in mammals . Johns Hopkins Med J 1972;;130:38-53.
Wachtel SS, Ohno S:  The immunogenetics of sexual development . Prog Med Genet 1979;; 3:109-142.
Wilson JD, Goldstein JL:  Classification of hereditary disorders of sexual development , in Bergsma D (ed): Genetic Forms of Hypogonadism . Birth defects original article series XI. New York, Stratton Intercontinental Medical Book Corp, 1975;, pp 1-16.
Wachtel SS:  The genetics of intersexuality: Clinical and theoretical perspectives . Obstet Gynecol 1979;;54:671-685.
Simpson JL:  Klinefelter syndrome , in Disorders of Sexual Differentiation: Etiology and Clinical Delineation . New York, Academic Press Inc, 1976;, pp 303-322.
Wachtel SS, Koo GC, Breg WR, et al:  Expression of H-Y antigen in human males with two Y-chromosomes . N Engl J Med 1975;; 293:1070-1072.
Cattanach BM: ' XO mice .' Genet Res 1962;; 3:487-490.
Short RV:  Sex determination and differentiation of the mammalian gonad . Int J Androl 1978;;2( (suppl) ):21-28.
Bernstein R, Koo GC, Wachtel SS:  Abnormality of the X chromosome in human 46,XY female siblings with dysgenetic ovaries . Science 1980;;207:768-769.
Bielert C, Bernstein R, Simon GB, et al:  XY gonadal dysgenesis in a chacma baboon . (Papio ursinus). Int J Primatol 1980;;1:3-13.
Koo GC, Wachtel SS, Krupen-Brown K, et al:  Mapping the locus of the H-Y gene on the human Y-chromosome . Science 1977;;198:940-942.
Rary JM, Cummings DK, Jones HW Jr, et al:  Assignment of the H-Y antigen gene to the short arm of chromosome Y . J Hered 1979;; 70:78-80.
Khodr GS, Gary DC, Teng C, et al:  Y-autosome translocation, gonadal dysgenesis and gonadoblastoma . Am J Dis Child 1979;;133:277-282.
German J, Simpson JL, Chaganti RSK, et al:  Genetically determined sex-reversal in 46,XY humans . Science 1978;;202:53-56.
Fredga K, Gropp A, Winking H, et al:  Fertile XX and XY type females in the wood lemming Myopus schisticolor . Nature 1976;; 261:225-227.
Wachtel SS, Koo GC, Ohno S, et al:  H-Y antigen and the origin of XY female wood lemmings (Myopus schisticolor) . Nature 1976;; 264:638-639.
Herbst EW, Fredga K, Frank F, et al:  Cytological identification of two X-chromosome types in the wood lemming (Myopus schisticolor) . Chromosoma 1978;;69:185-191.
Ghosh SN, Shah PN, Gharpure HM:  Absence of H-Y antigen in XY females with dysgenetic gonads . Nature 1978;;276:180-181.
Wachtel SS, Koo GC, de la Chapelle A, et al:  H-Y antigen in 46,XY gonadal dysgenesis . Hum Genet 1980;;54:25-30.
Ohno S:  The original function of MHC antigens as the general plasma membrane anchorage site of organogenesis-directing proteins . Immunol Rev 1977;;33:59-69.
Muller U, Aschmoneit I, Zenzes MT, et al:  Binding studies of H-Y antigen in rat tissues: Indications for a gonad-specific receptor . Hum Genet 1978;;43:151-157.
Hall BD, Spranger JW:  Campomelic dysplasia: Further elucidation of a distinct entity . Am J Dis Child 1980;;134:285-289.
De la Chapelle A, Hortling H, Niemi M, et al:  XX sex chromosomes in a human male: First case . Acta Med Scand 1964;;412( (suppl) ):25-38.
Miro R, Caballin MR, Marsini S, et al:  Mosaicism in XX males . Hum Genet 1978;;45:103-106.
Ferguson-Smith MA:  X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome . Lancet 1966;;2:475-475.
Pearson PL, Bobrow M:  Definitive evidence for the short arm of the Y chromosome associating with the X chromosome during meiosis in the human male . Nature 1970;;226:959-961.
Race RR, Sanger R:  Xg and sex chromosome aneuploidy , in Blood Groups in Man , ed 6. Oxford, England, Blackwell Scientific Publications, 1975;, pp 619-635.
Bernstein R, Wagner J, Isdale J, et al:  X-Y translocation in a retarded phenotypic male: Clinical, cytogenetic, biochemical and serogenetic studies . J Med Genet 1978;;15:466-474.
Bernstein R, Pinto MR, Almeida H, et al:  X-Y translocation in an adolescent mentally normal phenotypic male with features of hypogonadism . J Med Genet 1980;;17:437-443.
Evans HJ, Buckton KE, Spowart G, et al:  Heteromorphic X chromosomes in 46,XX males: Evidence for the involvement of X-Y interchange . Hum Genet 1979;;49:11-31.
Cattanach BM, Pollard CE, Hawkes SG:  Sex reversed mice: XX and XO males . Cytogenetics 1971;;10:318-337.
Basrur P-K, Kanagawa H:  Anatomic and cytogenetic studies on 19 hornless goats with sexual disorders . Ann Genet Paris 1969;;1:349-378.
De la Chapelle A, Schröder J, Murros J, et al:  Two XX males in one family and additional observations bearing on the etiology of XX males . Clin Genet 1977;;11:91-106.
Wachtel SS, Koo GC, Breg WR, et al:  Serologic detection of a Y-linked gene in XX males and XX true hermaphrodites . N Engl J Med 1976;;295:750-754.
Bennett D, Mathieson BJ, Scheid M, et al:  Serological evidence for H-Y antigen in Sxr, XX sex-reversed phenotypic males . Nature 1977;; 265:255-257.
Wachtel SS, Basrur P, Koo GC:  Recessive male-determining genes . Cell 1978;;15:279-281.
Van Niekerk WA:  Cytogenetic findings , in True Hermaphroditism: Clinical, Morphologic and Cytogenetic Aspects . Hagerstown, Md, Harper & Row Publishers Inc, 1974;, pp 129-141.
Selden JR, Wachtel SS, Koo GC, et al:  Genetic basis of XX male syndrome and XX true hermaphroditism: Evidence in the dog . Science 1978;;201:644-646.
Winters SJ, Wachtel SS, White BJ, et al:  H-Y antigen mosaicism in the gonad of a 46,XX true hermaphrodite . N Engl J Med 1979;;300:745-749.
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