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(genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors" (同)cistron, factor
the 19th letter of the Roman alphabet (同)s
informal term for information; "give me the gen on your new line of computers"

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遺伝子
sulfurの化学記号 / {略}South[ern]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/20 16:48:41」(JST)

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Testis-determining factor (TDF), also known as sex-determining region Y (SRY) protein, is a DNA-binding protein (also known as gene-regulatory 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 therians (placental mammals and marsupials);^[2] 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] SRY gene effects normally take place 6–8 weeks after foetus formation and inhibits the female anatomical structural growth in males. It also works towards developing the dominant male characteristics.

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 quickly 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

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 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]

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). Atypical genetic recombination during crossover when a sperm cell is developing can result in karyotypes that do not match their phenotypic expression.

Most of the time, when a developing sperm cell undergoes crossover during its meiosis, the SRY gene stays on the Y chromosome. If it is transferred to the X chromosome, however, the resulting Y chromosome will not have an SRY gene and can no longer initiate testis development. Offspring which inherit this Y chromosome will have Swyer syndrome, characterized by an XY karyotype 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 X chromosome will have a condition called XX male syndrome, characterized by an XX karyotype, and a male phenotype. While most XX males develop testis, is it possible for them to experience incomplete differentiation resulting in the formation of both testicular and ovarian tissues in the same individual. XX male syndrome results in infertility, 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 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]

References

^ Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (November 1990). "Genetic evidence equating SRY and the testis-determining factor". Nature 348 (6300): 448–50. Bibcode:1990Natur.348..448B. doi:10.1038/348448A0. PMID 2247149.
^ Wallis MC, Waters PD, Graves JA (June 2008). "Sex determination in mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95. doi:10.1007/s00018-008-8109-z. PMID 18581056.
^ ^a ^b ^c Kashimada K, Koopman P (December 2010). "Sry: the master switch in mammalian sex determination". Development 137 (23): 3921–30. doi:10.1242/dev.048983. PMID 21062860.
^ Mittwoch U (October 1988). "The race to be male". New Scientist 120 (1635): 38–42.
^ Katoh K, Miyata T (1999). "A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY". FEBS Lett 463 (1–2): 129–32. doi:10.1016/S0014-5793(99)01621-X. PMID 10601652.
^ Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (June 2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Res. 18 (6): 965–73. doi:10.1101/gr.7101908. PMC 2413164. PMID 18463302.
^ Bowles J, Schepers G, Koopman P (2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Dev Biol 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752.
^ ^a ^b ^c Ely D, Underwood A, Dunphy G, Boehme S, Turner M, Milsted A (November 2010). "Review of the Y chromosome, Sry and hypertension". Steroids 75 (11): 747–53. doi:10.1016/j.steroids.2009.10.015. PMC 2891862. PMID 19914267.
^ ^a ^b ^c ^d ^e ^f Harley VR, Clarkson MJ, Argentaro A (August 2003). "The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]". Endocr. Rev. 24 (4): 466–87. doi:10.1210/er.2002-0025. PMID 12920151.
^ Knower KC, Kelly S, Harley VR (2003). "Turning on the male--SRY, SOX9 and sex determination in mammals" (PDF). Cytogenet. Genome Res. 101 (3-4): 185–98. doi:10.1159/000074336. PMID 14684982.
^ Friedman, Theodore (2011). Advances in Genetics Vol 76. 108: Elsevier Inc.
^ ^a ^b McClelland K, Bowles J, Koopman P (January 2012). "Male sex determination: insights into molecular mechanisms". Asian J. Androl. 14 (1): 164–71. doi:10.1038/aja.2011.169. PMC 3735148. PMID 22179516.
^ Sekido R, Lovell-Badge R (2013). "Genetic control of testis development". Sex Dev 7 (1–3): 21–32. doi:10.1159/000342221. PMID 22964823.
^ Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (January 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". Am. J. Med. Genet. 90 (1): 25–8. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5. PMID 10602113.
^ Polanco JC, Koopman P (February 2007). "Sry and the hesitant beginnings of male development". Dev. Biol. 302 (1): 13–24. doi:10.1016/j.ydbio.2006.08.049. PMID 16996051.
^ Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene". Am. J. Hum. Genet. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780.
^ Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.
^ Lister Hill National Center for Biomedical Communications (2008). "Androgen insensitivity syndrome". Genetics Home Reference. U.S. National Library of Medicine.
^ Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (February 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Curr. Biol. 16 (4): 415–20. doi:10.1016/j.cub.2006.01.017. PMID 16488877.
^ ^a ^b "Olympic Gender Testing".
^ ^a ^b Facius GM (2004-08-01). "The Major Medical Blunder of the 20th Century". Gender Testing. facius-homepage.dk. Archived from the original on 26 January 2010. Retrieved 2011-06-12.
^ Elsas LJ, Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). "Gender verification of female athletes". Genet. Med. 2 (4): 249–54. doi:10.1097/00125817-200007000-00008. PMID 11252710.
^ Dickinson BD, Genel M, Robinowitz CB, Turner PL, Woods GL (October 2002). "Gender verification of female Olympic athletes". Med Sci Sports Exerc 34 (10): 1539–42; discussion 1543. doi:10.1097/00005768-200210000-00001. PMID 12370551.

External links

GeneReviews/NCBI/NIH/UW entry on 46,XX Testicular Disorder of Sex Development
OMIM entries on 46,XX Testicular Disorder of Sex Development
Genes, sry at the US National Library of Medicine Medical Subject Headings (MeSH)
Sex-Determining Region Y Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 正常な性的発育 normal sexual development
2. 外陰部異常を有する幼児の評価 evaluation of the infant with ambiguous genitalia
3. 性染色体異常 sex chromosome abnormalities
4. パーキンソン病の病因および発症機序 etiology and pathogenesis of parkinson disease
5. ターナー症候群（性腺発育不全）の臨床症状および診断 clinical manifestations and diagnosis of turner syndrome gonadal dysgenesis

English Journal

SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells.

Cai J1, Guan W1, Tan X1, Chen C1, Li L1, Wang N1, Zou X1, Zhou F1, Wang J1, Pei F1, Chen X1, Luo H1, Wang X1, He D1, Zhou L1, Jose PA2, Zeng C1.
Clinical science (London, England : 1979).Clin Sci (Lond).2015 Aug 1;129(3):259-69. doi: 10.1042/CS20140826.
We set out to investigate whether and how SRY (sex-determining region, Y) DNAs in plasma EVs (extracellular vesicles) is involved in the pathogenesis of atherosclerosis. PCR and gene sequencing found the SRY gene fragment in plasma EVs from male, but not female, patients; EVs from male patients with
PMID 25783200

Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction.

Ding Z1, Yang HW2, Xia TS3, Wang B4, Ding Q3.
International journal of molecular medicine.Int J Mol Med.2015 Aug;36(2):473-84. doi: 10.3892/ijmm.2015.2237. Epub 2015 Jun 5.
The RNA binding motif protein 38 (RBM38, also known as RNPC1) plays a pivotal role in regulating a wide range of biological processes, from cell proliferation and cell cycle arrest to cell myogenic differentiation. It was originally recognized as an oncogene, and was frequently found to be amplifie
PMID 26046131

First evidence of molecular characterization of rohu carp Sox2 gene being expressed in proliferating spermatogonial cells.

Patra SK1, Chakrapani V1, Panda RP1, Mohapatra C1, Jayasankar P1, Barman HK2.
Theriogenology.Theriogenology.2015 Jul 15;84(2):268-276.e1. doi: 10.1016/j.theriogenology.2015.03.017. Epub 2015 Mar 25.
Because little is known about the function of Sox2 (Sry-related box-2) in teleosts, the objective of this study was to clone and characterize Sox2 complementary DNA (cDNA) from the testis of Indian major carp, Labeo rohita (rohu). The full-length cDNA contained an open reading frame of 936 nucleotid
PMID 25913275

Japanese Journal

SRY-box-containing Gene 2 Regulation of Nuclear Receptor Tailless (Tlx) Transcription in Adult Neural Stem Cells

Shimozaki Koji,Zhang Chun-Li,Suh Hoonkyo,Denli Ahmet M.,Evans Ronald M.,Gage Fred H.
Journal of Biological Chemistry 287(8), 5969-5978, 2012-02-17
… Here we show that SRY-box-containing gene 2 (Sox2) and nuclear receptor tailless (TLX) form a molecular network in adult NSCs. … We observed that both Sox2 and TLX proteins bind to the upstream region of Tlx gene. …
NAID 120004270892

Spatial Framework of Nine Distinct Local Populations of the Japanese Dormouse Glirulus japonicus Based on Matrilineal Cytochrome b and Patrilineal SRY Gene Sequences

Yasuda Shumpei P.,Iwabuchi Manami,Aiba Haruka [他]
Zoological science 29(2), 111-120, 2012-02
NAID 40019149517

Related Pictures

The SRY gene on X chromosome | Download Scientific Diagram Sry: the master switch in mammalian sex determination | Development PPT - Meet The Fugates PowerPoint Presentation, free download - ID:4058132 Switching on sex: Mastered by SRY gene Steroidogenic Factor 1 PPT - Sex Determination PowerPoint Presentation - ID:2095001 Genetics - Fall 2002 Genetics chapter 3 part 2

★リンクテーブル★

リンク元	「SRY遺伝子」
関連記事	「SR」「S」

「SRY遺伝子」

Sex-determining region Y
	PDB rendering based on 1hry.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1HRY, 1HRZ, 1J46, 1J47, 2GZK
Identifiers
Symbols	SRY ; SRXX1; SRXY1; TDF; TDY
External IDs	OMIM: 480000 MGI: 98660 HomoloGene: 48168 GeneCards: SRY Gene
Gene ontology
Molecular function	• DNA binding; • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; • calmodulin binding; • transcription factor binding; • DNA binding, bending; • protein heterodimerization activity;
Cellular component	• nucleus; • nucleoplasm; • cytoplasm; • nuclear speck; • nuclear transcription factor complex;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • transcription, DNA-templated; • male gonad development; • cell differentiation; • male sex determination; • positive regulation of transcription, DNA-templated; • positive regulation of male gonad development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: SRY gene
同: 性決定遺伝子 sex determining gene、精巣決定遺伝子 TDF gene testis-determining factor gene
関: 性染色体、精巣決定遺伝子群

「SR」

　　[★]

筋小胞体 sarcoplasmic reticula sarcoplasmic reticulum

「S」

　　[★]

[TDF-1] Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (November 1990). "Genetic evidence equating SRY and the testis-determining factor". Nature 348 (6300): 448–50. Bibcode:1990Natur.348..448B. doi:10.1038/348448A0. PMID 2247149.

[pmid18581056-2] Wallis MC, Waters PD, Graves JA (June 2008). "Sex determination in mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95. doi:10.1007/s00018-008-8109-z. PMID 18581056.

[Kashimada_Koopman_2010-3] Kashimada K, Koopman P (December 2010). "Sry: the master switch in mammalian sex determination". Development 137 (23): 3921–30. doi:10.1242/dev.048983. PMID 21062860.

[Mittwoch_1988-4] Mittwoch U (October 1988). "The race to be male". New Scientist 120 (1635): 38–42.

[5] Katoh K, Miyata T (1999). "A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY". FEBS Lett 463 (1–2): 129–32. doi:10.1016/S0014-5793(99)01621-X. PMID 10601652.

[pmid18463302-6] Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (June 2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Res. 18 (6): 965–73. doi:10.1101/gr.7101908. PMC 2413164. PMID 18463302.

[7] Bowles J, Schepers G, Koopman P (2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Dev Biol 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752.

[pmid19914267-8] Ely D, Underwood A, Dunphy G, Boehme S, Turner M, Milsted A (November 2010). "Review of the Y chromosome, Sry and hypertension". Steroids 75 (11): 747–53. doi:10.1016/j.steroids.2009.10.015. PMC 2891862. PMID 19914267.

[Harley_2003-9] ^ ^a ^b ^c ^d ^e ^f Harley VR, Clarkson MJ, Argentaro A (August 2003). "The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]". Endocr. Rev. 24 (4): 466–87. doi:10.1210/er.2002-0025. PMID 12920151.

[pmid14684982-10] Knower KC, Kelly S, Harley VR (2003). "Turning on the male--SRY, SOX9 and sex determination in mammals" (PDF). Cytogenet. Genome Res. 101 (3-4): 185–98. doi:10.1159/000074336. PMID 14684982.

[11] Friedman, Theodore (2011). Advances in Genetics Vol 76. 108: Elsevier Inc.

[pmid22179516-12] McClelland K, Bowles J, Koopman P (January 2012). "Male sex determination: insights into molecular mechanisms". Asian J. Androl. 14 (1): 164–71. doi:10.1038/aja.2011.169. PMC 3735148. PMID 22179516.

[pmid22964823-13] Sekido R, Lovell-Badge R (2013). "Genetic control of testis development". Sex Dev 7 (1–3): 21–32. doi:10.1159/000342221. PMID 22964823.

[pmid10602113-14] Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (January 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". Am. J. Med. Genet. 90 (1): 25–8. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5. PMID 10602113.

[pmid16996051-15] Polanco JC, Koopman P (February 2007). "Sry and the hesitant beginnings of male development". Dev. Biol. 302 (1): 13–24. doi:10.1016/j.ydbio.2006.08.049. PMID 16996051.

[pmid19361780-16] Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene". Am. J. Hum. Genet. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780.

[pmid11585838-17] Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.

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SRY gene