Testis determining factor - Wikipedia, the free encyclopedia
http://en.wikipedia.org/wiki/Testis_determining_factor
Testis determining factor
From Wikipedia, the free encyclopedia
Testisdetermining
factor (TDF),
also known as
sex-determining
region Y (SRY)
protein, is a
DNA-binding
protein (also
known as
gene-regulatory
Sex determining region Y
PDB rendering based on 1hry.
Available structures
PDB
Ortholog search: PDBe (http://www.ebi.ac.uk/pdbe/searchResults.html?display=both&
term=A7WPU8%20or%20Q05066%20or%20Q28798%20or%20F2YKT8%20or%20Q03255%20or%20B6S2A2), RCSB
(http://www.rcsb.org/pdb/search/smartSubquery.do?smartSearchSubtype=UpAccessionIdQuery&
accessionIdList=A7WPU8,Q05066,Q28798,F2YKT8,Q03255,B6S2A2)
List of PDB id codes
1HRY (http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1HRY), 1HRZ (http://www.rcsb.org/pdb/cgi
/explore.cgi?pdbId=1HRZ), 1J46 (http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1J46), 1J47 (http://www.rcsb.org/pdb/cgi
/explore.cgi?pdbId=1J47), 2GZK (http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2GZK)
Identifiers
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Symbols SRY (http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=11311) ; SRXX1; SRXY1; TDF; TDY
External OMIM: 480000 (https://omim.org/entry/480000) MGI: 98660 (http://www.informatics.jax.org/marker/MGI:98660)
IDs
HomoloGene: 48168 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=HomoloGene&
list_uids=48168) GeneCards: SRY Gene (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=6736)
Gene ontology
Molecular
function
• DNA binding (http://amigo.geneontology.org/amigo/term/GO:0003677)
• RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
(http://amigo.geneontology.org/amigo/term/GO:0003705)
• calmodulin binding (http://amigo.geneontology.org/amigo/term/GO:0005516)
• transcription factor binding (http://amigo.geneontology.org/amigo/term/GO:0008134)
component
• nucleus (http://amigo.geneontology.org/amigo/term/GO:0005634)
• cytoplasm (http://amigo.geneontology.org/amigo/term/GO:0005737)
• nuclear speck (http://amigo.geneontology.org/amigo/term/GO:0016607)
Biological
• regulation of transcription from RNA polymerase II promoter (http://amigo.geneontology.org/amigo
process
/term/GO:0006357)
Cellular
• transcription from RNA polymerase II promoter (http://amigo.geneontology.org/amigo/term/GO:0006366)
• sex differentiation (http://amigo.geneontology.org/amigo/term/GO:0007548)
• cell differentiation (http://amigo.geneontology.org/amigo/term/GO:0030154)
• male sex determination (http://amigo.geneontology.org/amigo/term/GO:0030238)
• positive regulation of transcription, DNA-templated (http://amigo.geneontology.org/amigo/term/GO:0045893)
• positive regulation of male gonad development (http://amigo.geneontology.org/amigo/term/GO:2000020)
Sources: Amigo (http://amigo.geneontology.org/cgi-bin/amigo/gp-assoc.cgi?gp=UniProtKB:Q05066) / QuickGO (http://www.ebi.ac.uk
/QuickGO/GProtein?ac=Q05066)
RNA expression pattern
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More reference expression data (http://biogps.org/gene/6736/)
Orthologs
Species
Human
Mouse
Entrez
6736 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=6736&rn=1) n/a
Ensembl ENSG00000184895 (http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000184895;db=core)
n/a
UniProt Q05066 (http://www.uniprot.org/uniprot/Q05066)
n/a
RefSeq
NM_003140 (http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_003140)
n/a
NP_003131 (http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_003131)
n/a
(mRNA)
RefSeq
(protein)
Location Chr Y:
n/a
(UCSC) 2.65 – 2.66 Mb (http://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg19&position=chrY:2654896-2655740)
PubMed [1] (http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=6736)
n/a
search
protein/transcription factor) encoded by the SRY gene that is responsible for the initiation of male sex determination in humans.[1] SRY is an
intronless sex-determining gene on the Y chromosome in the therians (placental mammals and marsupials),[2] and mutations in this gene lead to
a range of sex-related disorders with varying effects on an individual's phenotype and genotype. TDF is a member of the SOX (SRY-like box)
gene family of DNA-binding proteins. When complexed with the SF1 protein, TDF acts as a transcription factor that can upregulate other
transcription factors, most importantly SOX9.[3] Its expression causes the development of primary sex cords, which later develop into
seminiferous tubules. These cords form in the central part of the yet-undifferentiated gonad, turning it into a testis. The now induced Leydig
cells of the testis then start secreting testosterone while the Sertoli cells produce anti-Müllerian hormone.[4]
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Contents
1 Gene evolution and regulation
1.1 Evolution
1.2 Regulation
2 Function
2.1 Action in the nucleus
2.2 SOX9 and testes differentiation
3 Influence on sex
3.1 Role in other diseases
3.2 Use in Olympic screening
3.3 Ongoing research
4 See also
5 References
6 Further reading
7 External links
Gene evolution and regulation
Evolution
SRY may have arisen from a gene duplication of the X chromosome bound gene SOX3, a member of the Sox family.[5] This duplication occurred
after the split between monotremes and therians. Monotremes lack SRY and have a ZW-like sex determination system, likely involving DMRT1,
whereas therians (marsupials and placental mammals) use the XY sex determination system.[6] SRY is a rapidly evolving gene and its regulation
has been difficult to study because sex determination is not a highly conserved phenomenon within the animal kingdom. [7]
Regulation
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SRY gene has little in common with sex determination genes of other model organisms, and mice are the main model research organisms that
can be utilized for its study . Understanding its regulation is further complicated because even between mammalian species, there is little protein
sequence conservation. The only conserved group between mice and mammals is the High-mobility Group (HMG) box region that is
responsible for DNA binding. Mutations in this region result in sex reversal, where the opposite sex is produced.[8] Because there is little
conservation, the SRY promoter, regulatory elements and regulation are not well understood. Within related mammalian groups there are
homologies within the first 400-600 base pairs upstream from the translational start site. In vitro studies of human SRY promoter have shown
that a region of at least 310 bp upstream to translational start site are required for SRY promoter function. It's been shown that binding of three
transcription factors, Steroidogenic factor 1 (SF1), Specificity Protein 1 (Sp1 transcription factor) and Wilms tumor protein 1 (WT1), to the
human promoter sequence, influence expression of SRY.[8]
The promoter region has two Sp1 binding sites, at -150 and -13 that function as regulatory sites. Sp1 is a transcription factor that binds GC-rich
consensus sequences, and mutation of the SRY binding sites leads to a 90% reduction in gene transcription. Studies of SF1 have resulted in less
definite results . Mutations of SF1 can lead to sex reversal and deletion lead to incomplete gonad development. However, it's not clear how SF1
interacts with the SR1 promoter directly.[9] The promoter region also has two WT1 binding sites at -78 and -87 bp from the ATG codon. WT1 is
transcription factor that has four C-terminal Zinc fingers and an N-terminal Pro/Glu-rich region and primarily functions as an activator. Mutation
of the Zinc fingers or inactivation of WT1 results in reduced male gonad size. Deletion of the gene resulted in complete sex reversal. It is not
clear how WT1 functions to up-regulate SRY, but some research suggests that it helps stabilize message processing.[9] However, there are
complications to this hypothesis, because WT1 also is responsible for expression of an antagonist of male development, DAX1, which stands for
Dosage-sensitive sex reversal, Adrenal hypoplasia critical region, on chromosome X, gene 1 . An additional copy of DAX1 in mice leads to sex
reversal. It is not clear how DAX1 functions, and many different pathways have been suggested, including SRY transcriptional destabilization
and RNA binding. There is evidence from work on suppression of male development that DAX1 can interfere with function of SF1, and in turn
transcription of SRY by recruiting corepressors.[8]
There is also evidence that GATA binding protein 4 (GATA4) and FOG2 contribute to activation of SRY by associating with its promoter. How
these proteins regulate SRY transcription is not clear, but FOG2 and GATA4 mutants have significantly lower levels of SRY transcription.[10]
FOGs have zinc finger motifs that can bind DNA, but there is no evidence of FOG2 interaction with SRY. Studies suggest that FOG2 and
GATA4 associate with nucleosome remodeling proteins that could lead to its activation.[11]
Function
During gestation, the cells of the primordial gonad that lie along the urogenital ridge are in a bipotential state, meaning they possess the ability to
become either male cells (Sertoli and Leydig cells) or female cells (follicle cells and Theca cells). TDF initiates testis differentiation by
activating male-specific transcription factors that allow these bipotential cells to differentiate and proliferate. TDF accomplishes this by
upregulating SOX9, a transcription factor with a DNA-binding site very similar to TDF's. SOX9 leads to the upregulation of fibroblast growth
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factor 9 (Fgf9), which in turn leads to further upregulation of SOX9 . Once proper SOX9 levels are reached, the bipotential cells of the gonad
begin to differentiate into Sertoli cells. Additionally, cells expressing TDF will continue to proliferate to form the primordial testis. While this
constitutes the basic series of events, this brief review should be taken with caution since there are many more factors that influence sex
differentiation.
Action in the nucleus
The TDF protein consists of three main regions. The central region encompasses the HMG (high-motility group) domain, which contains
nuclear localization sequences and acts as the DNA-binding domain. The C-terminal domain has no conserved structure, and the N-terminal
domain can be phosphorylated to enhance DNA-binding.[9] The process begins with nuclear localization of TDF by acetylation of the nuclear
localization signal regions, which allows for the binding of importin β and calmodulin to TDF, facilitating its import into the nucleus. Once in
the nucleus, TDF and SF1 (steroidogenic factor 1, another transcriptional regulator) complex and bind to TESCO (testis-specific enhancer of
Sox9 core), the testes-specific enhancer element of the Sox9 gene in Sertoli cell precursors, located upstream of the Sox9 gene transcription start
site.[3] Specifically, it is the HMG region of TDF that binds to the minor groove of the DNA target sequence, causing the DNA to bend and
unwind. The establishment of this particular DNA “architecture” facilitates the transcription of the Sox9 gene.[9] SOX9 protein then initiates a
positive feedback loop, involving SOX9 acting as its own transcription factor and resulting in the synthesis of large amounts of SOX9.[9]
SOX9 and testes differentiation
The SF1 protein, on its own, leads to minimal transcription of the SOX9 gene in both the XX and XY bipotential gonadal cells along the
urogenital ridge. However, binding of the TDF-SF1 complex to the testis-specific enhancer (TESCO) on SOX9 leads to significant up-regulation
of the gene in only the XY gonad, while transcription in the XX gonad remains negligible. Part of this up-regulation is accomplished by SOX9
itself through a positive feedback loop; like TDF, SOX9 complexes with SF1 and binds to the TESCO enhancer, leading to further expression of
SOX9 in the XY gonad. Two other proteins, FGF9 (fibroblast growth factor 9) and PDG2 (prostaglandin D2), also maintain this up-regulation.
Although their exact pathways are not fully understood, they have been proven to be essential for the continued expression of SOX9 at the levels
necessary for testes development.[3]
SOX9 and TDF are believed to be responsible for the cell-autonomous differentiation of supporting cell precursors in the gonads into Sertoli
cells, the beginning of testes development. These initial Sertoli cells, in the center of the gonad, are hypothesized to be the starting point for a
wave of FGF9 that spreads throughout the developing XY gonad, leading to further differentiation of Sertoli cells via the up-regulation of
SOX9.[12] SOX9 and TDF are also believed to be responsible for many of the later processes of testis development (such as Leydig cell
differentiation, sex cord formation, and formation of testis-specific vasculature), although exact mechanisms remain unclear.[13] It has been
shown, however, that SOX9, in the presence of PDG2, acts directly on Amh (encoding anti-Müllerian hormone) and is capable of inducing testis
formation in XX mice gonads, indicating its vital to testes development.[12]
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Influence on sex
Embryos are gonadally identical, regardless of genetic sex, until a certain point in development when the testis-determining factor causes male
sex organs to develop. Therefore, SRY plays an important role in sex determination. A typical male karyotype is XY. Individuals who inherit a
normal Y chromosome and multiple X chromosomes are generally male (such as in Klinefelter Syndrome, which has an XXY karyotype). A
genetic recombination event known as crossing over can result in karyotypes that do not match their phenotypic expression.
Crossing over during paternal meiosis prior to conception can cause SRY to be transferred from the Y chromosome to the X chromosome. The
Y chromosome that results from this crossover is now lacking an SRY gene, and can no longer initiate testis development. When this
chromosome is inherited from the father, the resulting offspring will have Swyer syndrome, characterized by a male karyotype (XY) and a
female phenotype. The X chromosome that results from this crossover event now has a SRY gene, and therefore the ability to initiate testis
development. Offspring who inherit this chromosome will have a condition called XX male syndrome, characterized by an XX karyotype, and a
male phenotype. While most XX males develop phenotypically as males, is it possible for them to experience incomplete differentiation of the
testis, resulting in the formation of both testicular and ovarian in the same individual. This true sterile hermaphroditism (not to be confused with
the hermaphroditism of hermaphroditic species and taxa such as earthworms, as they can reproduce) is most likely caused by the inactivation
(either random or non-random) of the X chromosome containing the SRY in some cells.[14]
While the presence or absence of SRY has generally determined whether or not testis development occurs, it has been suggested that there are
other factors that affect the functionality of SRY.[15] Therefore, there are individuals who have the SRY gene, but still develop as females, either
because the gene itself is defective or mutated, or because one of the contributing factors is defective.[16] This can happen in individuals
exhibiting a XY, XXY, or XX SRY-positive karyotype.
Role in other diseases
SRY has been shown to interact with the androgen receptor and individuals with XY karyotype and a functional SRY gene can have an
outwardly female phenotype due to an underlying androgen insensitivity syndrome (AIS).[17] Individuals with AIS are unable to respond to
androgens properly due to a defect in their androgen receptor gene, and affected individuals can have complete or partial AIS.[18] SRY has also
been linked to the fact that males are more likely than females to develop dopamine-related diseases such as schizophrenia and Parkinson's
disease. SRY encodes a protein that controls the concentration of dopamine, the neurotransmitter that carries signals from the brain that control
movement and coordination.[19]
Use in Olympic screening
One of the most controversial uses of this discovery was as a means for gender verification at the Olympic Games, under a system implemented
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by the International Olympic Committee in 1992. Athletes with an SRY gene were not permitted to participate as females, although all athletes
in whom this was "detected" at the 1996 Summer Olympics were ruled false positives and were not disqualified. Specifically, eight female
participants (out of a total of 3387) at these games were found to have the SRY gene. However, after further investigation of their genetic
conditions, all these athletes were verified as female and allowed to compete. These athletes were found to have either partial or full androgen
insensitivity, despite having an SRY gene, making them phenotypically female and giving them no advantage over other female competitors.[20]
In the late 1990s, a number of relevant professional societies in United States called for elimination of gender verification, including the
American Medical Association, stating that the method used was uncertain and ineffective.[21] The screening was eliminated as of the 2000
Summer Olympics.[21][22][23] Since this method of testing was eliminated there has been no form of Olympic gender screening that all athletes
must undergo. Rather, questions regarding an athlete's gender are now addressed on an individual basis by medical experts, only when there is
significant reason to suspect a male athlete may be posing as a female. However, there have been few, if any, instances of such suspicion and
evaluation since the system of screening was eliminated, due to the difficulties and impracticality of a male successfully disguising himself as a
female athlete (such as the nature of women's event uniforms, which make concealment of a male's body near impossible).[20]
Ongoing research
Despite the progress made during the past several decades in the study of sex determination, the SRY gene, and the TDF protein, work is still
being done to further our understanding in these areas. There remain factors that need to be identified in the sex-determining molecular network,
and the chromosomal changes involved in many other human sex-reversal cases are still unknown. Scientists continue to search for additional
sex-determining genes, using techniques such as microarray screening of the genital ridge genes at varying developmental stages, mutagenesis
screens in mice for sex-reversal phenotypes, and identifying the genes that transcription factors act on using chromatin immunoprecipitation.[9]
See also
Y chromosome
Sex-determination system
References
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Testis determining factor - Wikipedia, the free encyclopedia
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Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). "Gender
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verification of female athletes". Genet. Med. 2 (4): 249–54.
Sci Sports Exerc 34 (10): 1539–42; discussion 1543.
doi:10.1097/00125817-200007000-00008 (http://dx.doi.org
doi:10.1097/00005768-200210000-00001 (http://dx.doi.org
/10.1097%2F00125817-200007000-00008). PMID 11252710
/10.1097%2F00005768-200210000-00001). PMID 12370551
(https://www.ncbi.nlm.nih.gov/pubmed/11252710).
(https://www.ncbi.nlm.nih.gov/pubmed/12370551).
Further reading
Haqq CM, King CY, Ukiyama E, Falsafi S, Haqq TN, Donahoe PK,
Harley VR (2002). "The molecular action of testis-determining factors
Weiss MA (December 1994). "Molecular basis of mammalian sexual
SRY and SOX9". Novartis Found. Symp. Novartis Foundation
determination: activation of Müllerian inhibiting substance gene
Symposia 244: 57–66; discussion 66–7, 79–85, 253–7.
expression by SRY". Science 266 (5190): 1494–500.
doi:10.1002/0470868732.ch6 (http://dx.doi.org
doi:10.1126/science.7985018 (http://dx.doi.org
/10.1002%2F0470868732.ch6). ISBN 978-0-470-86873-7.
/10.1126%2Fscience.7985018). PMID 7985018
PMID 11990798 (https://www.ncbi.nlm.nih.gov/pubmed/11990798).
(https://www.ncbi.nlm.nih.gov/pubmed/7985018).
Jordan BK, Vilain E (2003). "Sry and the genetics of sex
Goodfellow PN, Lovell-Badge R (1993). "SRY and sex determination
determination". Adv. Exp. Med. Biol. Advances in Experimental
in mammals". Annu. Rev. Genet. 27: 71–92.
Medicine and Biology 511: 1–13; discussion 13–4.
doi:10.1146/annurev.ge.27.120193.000443 (http://dx.doi.org
doi:10.1007/978-1-4615-0621-8_1 (http://dx.doi.org
/10.1146%2Fannurev.ge.27.120193.000443). PMID 8122913
/10.1007%2F978-1-4615-0621-8_1). ISBN 978-1-4613-5162-7.
(https://www.ncbi.nlm.nih.gov/pubmed/8122913).
PMID 12575752 (https://www.ncbi.nlm.nih.gov/pubmed/12575752).
Hawkins JR (1993). "Mutational analysis of SRY in XY females". Hum.
Oh HJ, Lau YF (2006). "KRAB: a partner for SRY action on
Mutat. 2 (5): 347–50. doi:10.1002/humu.1380020504 (http://dx.doi.org
chromatin". Mol. Cell. Endocrinol. 247 (1–2): 47–52.
/10.1002%2Fhumu.1380020504). PMID 8257986
doi:10.1016/j.mce.2005.12.011 (http://dx.doi.org
(https://www.ncbi.nlm.nih.gov/pubmed/8257986).
/10.1016%2Fj.mce.2005.12.011). PMID 16414182
(https://www.ncbi.nlm.nih.gov/pubmed/16414182).
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http://en.wikipedia.org/wiki/Testis_determining_factor
Polanco JC, Koopman P (2007). "Sry and the hesitant beginnings of
Vilain E, McElreavey K, Jaubert F, Raymond JP, Richaud F, Fellous M
male development". Dev. Biol. 302 (1): 13–24.
(May 1992). "Familial case with sequence variant in the testis-
doi:10.1016/j.ydbio.2006.08.049 (http://dx.doi.org
determining region associated with two sex phenotypes"
/10.1016%2Fj.ydbio.2006.08.049). PMID 16996051
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682588). Am. J.
(https://www.ncbi.nlm.nih.gov/pubmed/16996051).
Hum. Genet. 50 (5): 1008–11. PMC 1682588
Hawkins JR, Taylor A, Berta P, Levilliers J, Van der Auwera B,
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682588).
Goodfellow PN (February 1992). "Mutational analysis of SRY:
PMID 1570829 (https://www.ncbi.nlm.nih.gov/pubmed/1570829).
nonsense and missense mutations in XY sex reversal". Hum. Genet. 88
Müller J, Schwartz M, Skakkebaek NE (July 1992). "Analysis of the
(4): 471–4. doi:10.1007/BF00215684 (http://dx.doi.org
sex-determining region of the Y chromosome (SRY) in sex reversed
/10.1007%2FBF00215684). PMID 1339396
patients: point-mutation in SRY causing sex-reversion in a 46,XY
(https://www.ncbi.nlm.nih.gov/pubmed/1339396).
female". J. Clin. Endocrinol. Metab. 75 (1): 331–3.
Hawkins JR, Taylor A, Goodfellow PN, Migeon CJ, Smith KD,
doi:10.1210/jc.75.1.331 (http://dx.doi.org/10.1210%2Fjc.75.1.331).
Berkovitz GD (November 1992). "Evidence for increased prevalence of
PMID 1619028 (https://www.ncbi.nlm.nih.gov/pubmed/1619028).
SRY mutations in XY females with complete rather than partial gonadal
McElreavey KD, Vilain E, Boucekkine C, Vidaud M, Jaubert F,
dysgenesis" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682856).
Richaud F, Fellous M (July 1992). "XY sex reversal associated with a
Am. J. Hum. Genet. 51 (5): 979–84. PMC 1682856
nonsense mutation in SRY". Genomics 13 (3): 838–40.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682856).
doi:10.1016/0888-7543(92)90164-N (http://dx.doi.org
PMID 1415266 (https://www.ncbi.nlm.nih.gov/pubmed/1415266).
/10.1016%2F0888-7543%2892%2990164-N). PMID 1639410
Ferrari S, Harley VR, Pontiggia A, Goodfellow PN, Lovell-Badge R,
(https://www.ncbi.nlm.nih.gov/pubmed/1639410).
Bianchi ME (December 1992). "SRY, like HMG1, recognizes sharp
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ,
angles in DNA" (https://www.ncbi.nlm.nih.gov/pmc/articles
Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN (July 1990).
/PMC557025). EMBO J. 11 (12): 4497–506. PMC 557025
"A gene from the human sex-determining region encodes a protein with
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC557025).
homology to a conserved DNA-binding motif". Nature 346 (6281):
PMID 1425584 (https://www.ncbi.nlm.nih.gov/pubmed/1425584).
240–4. doi:10.1038/346240a0 (http://dx.doi.org
Jäger RJ, Harley VR, Pfeiffer RA, Goodfellow PN, Scherer G
/10.1038%2F346240a0). PMID 1695712 (https://www.ncbi.nlm.nih.gov
(December 1992). "A familial mutation in the testis-determining gene
/pubmed/1695712).
SRY shared by both sexes". Hum. Genet. 90 (4): 350–5.
doi:10.1007/BF00220457 (http://dx.doi.org/10.1007%2FBF00220457).
PMID 1483689 (https://www.ncbi.nlm.nih.gov/pubmed/1483689).
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http://en.wikipedia.org/wiki/Testis_determining_factor
Berkovitz GD, Fechner PY, Zacur HW, Rock JA, Snyder HM, Migeon
Ellis NA, Goodfellow PJ, Pym B, Smith M, Palmer M, Frischauf AM,
CJ, Perlman EJ (November 1991). "Clinical and pathologic spectrum of
Goodfellow PN (January 1989). "The pseudoautosomal boundary in
46,XY gonadal dysgenesis: its relevance to the understanding of sex
man is defined by an Alu repeat sequence inserted on the Y
differentiation". Medicine (Baltimore) 70 (6): 375–83.
chromosome". Nature 337 (6202): 81–4. doi:10.1038/337081a0
doi:10.1097/00005792-199111000-00003 (http://dx.doi.org
(http://dx.doi.org/10.1038%2F337081a0). PMID 2909893
/10.1097%2F00005792-199111000-00003). PMID 1956279
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(https://www.ncbi.nlm.nih.gov/pubmed/1956279).
Whitfield LS, Hawkins TL, Goodfellow PN, Sulston J (May 1995). "41
Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow
kilobases of analyzed sequence from the pseudoautosomal and
PN, Fellous M (November 1990). "Genetic evidence equating SRY and
sex-determining regions of the short arm of the human Y chromosome".
the testis-determining factor". Nature 348 (6300): 448–50.
Genomics 27 (2): 306–11. doi:10.1006/geno.1995.1047
doi:10.1038/348448A0 (http://dx.doi.org/10.1038%2F348448A0).
(http://dx.doi.org/10.1006%2Fgeno.1995.1047). PMID 7557997
PMID 2247149 (https://www.ncbi.nlm.nih.gov/pubmed/2247149).
(https://www.ncbi.nlm.nih.gov/pubmed/7557997).
Jäger RJ, Anvret M, Hall K, Scherer G (November 1990). "A human
XY female with a frame shift mutation in the candidate testisdetermining gene SRY". Nature 348 (6300): 452–4.
doi:10.1038/348452a0 (http://dx.doi.org/10.1038%2F348452a0).
PMID 2247151 (https://www.ncbi.nlm.nih.gov/pubmed/2247151).
External links
GeneReviews/NCBI/NIH/UW entry on 46,XX Testicular Disorder of Sex Development (http://www.ncbi.nlm.nih.gov/books/NBK1416/)
OMIM entries on 46,XX Testicular Disorder of Sex Development (http://www.ncbi.nlm.nih.gov/omim/278850,480000,278850,480000)
Genes, sry (https://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Genes,+sry) at the US National Library of Medicine Medical
Subject Headings (MeSH)
Sex-Determining Region Y Protein (https://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=SexDetermining+Region+Y+Protein) at the US National Library of Medicine Medical Subject Headings (MeSH)
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Testis determining factor - Wikipedia, the free encyclopedia
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Categories: Human proteins Transcription factors Mammal genes Genes on chromosome Y Human genes Epigenetics
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