SRY

From Wikipedia, the free encyclopedia

This article is about the SRY gene. For other uses, see SRY (disambiguation).
Sex determining region Y
PDB rendering based on 1hry.
Available structures: 1hry, 1hrz, 1j46, 1j47
Identifiers
Symbol(s) SRY; TDF; TDY
External IDs OMIM: 480000 MGI: 98660 HomoloGene: 48168
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 6736 21674
Ensembl ENSG00000184895 ENSMUSG00000069036
Uniprot Q05066 Q2T9H0
Refseq NM_003140 (mRNA)
NP_003131 (protein)		 NM_011564 (mRNA)
NP_035694 (protein)
Location Chr Y: 2.71 - 2.72 Mb Chr Y: 1.95 - 1.95 Mb
Pubmed search [1] [2]

SRY (Sex-determining Region Y) is a sex-determining gene on the Y chromosome in humans and other primates.

The SRY gene encodes the testis determining factor, which is also referred to as the SRY protein.

This intronless gene encodes a transcription factor that is a member of the high mobility group (HMG)-box family of DNA-binding proteins. This protein is the testis-determining factor (TDF), which initiates male sex determination. Mutations in this gene give rise to XY females with gonadal dysgenesis (Swyer syndrome); translocation of part of the Y chromosome containing this gene to the X chromosome causes XX male syndrome.[1]

Contents

[edit] Impact upon anatomical sex

Since its discovery, the importance of the SRY gene in sex determination has been extensively documented:

  • Humans with one Y chromosome and multiple X chromosomes (XXY, XXXY etc.) are usually males.
  • Individuals with a male phenotype and an XX (female) genotype have been observed; these males have the SRY gene in one or both X chromosomes, moved there by chromosomal translocation. (However, these males are infertile.)
  • Similarly, there are females with an XXY or XY genotype. These females have no SRY gene in their Y chromosome, or the SRY gene exists but is defective (mutated).

[edit] SRY and the Olympics

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 a 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. In the late 1990s, a number of relevant professional societies in United States called for elimination of gender verification, including the American Medical Association, the American Academy of Pediatrics, the American College of Physicians, the American College of Obstetricians and Gynecologists, the Endocrine Society and the American Society of Human Genetics, stating that the method used was uncertain and ineffective.[2] The screening was eliminated as of the 2000 Summer Olympics.[2][3][4]

[edit] SRY-related diseases and defects

Individuals with XY genotype and functional SRY gene can have a female phenotype, where the underlying cause is androgen insensitivity syndrome (AIS).

SRY has been linked to the fact that men are more likely than women to develop dopamine-related diseases such as schizophrenia and Parkinson's disease. SRY makes a protein that controls concentrations of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination.[5][6]

[edit] See also

[edit] References

  1. ^ Entrez Gene: SRY sex determining region Y.
  2. ^ a b Facius, Georg M. (August 2004). The Major Medical Blunder of the 20th Century. Bodies Like Ours. Retrieved on May 30, 2006.
  3. ^ Elsas, LJ; Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (July-August 2000). "Gender verification of female athletes". Genetics in Medicine 2 (4): 249-54. PMID 11252710. 
  4. ^ Dickinson, BD; Genel M, Robinowitz CB, Turner PL, Woods GL (October 2002). "Gender verification of female Olympic athletes". Medicine & Science in Sports & Exercise 34 (10): 1543. PMID 12370551. 
  5. ^ Dewing, P; Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (Feb 21 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Current Biology 16 (4): 415-20. PMID 16488877. 
  6. ^ Haaxma, C., et al. (Feb. 22-26, 2006). "Gender differences in Parkinson's disease". 1st World Parkinson Congress. 

[edit] Further reading

  • Haqq CM, King CY, Ukiyama E, et al. (1995). "Molecular basis of mammalian sexual determination: activation of Müllerian inhibiting substance gene expression by SRY.". Science 266 (5190): 1494-500. PMID 7985018. 
  • Goodfellow PN, Lovell-Badge R (1994). "SRY and sex determination in mammals.". Annu. Rev. Genet. 27: 71-92. doi:10.1146/annurev.ge.27.120193.000443. PMID 8122913. 
  • Hawkins JR (1994). "Mutational analysis of SRY in XY females.". Hum. Mutat. 2 (5): 347-50. doi:10.1002/humu.1380020504. PMID 8257986. 
  • Harley VR (2002). "The molecular action of testis-determining factors SRY and SOX9.". Novartis Found. Symp. 244: 57-66; discussion 66-7, 79-85, 253-7. PMID 11990798. 
  • Jordan BK, Vilain E (2003). "Sry and the genetics of sex determination.". Adv. Exp. Med. Biol. 511: 1-13; discussion 13-4. PMID 12575752. 
  • Oh HJ, Lau YF (2006). "KRAB: a partner for SRY action on chromatin.". Mol. Cell. Endocrinol. 247 (1-2): 47-52. doi:10.1016/j.mce.2005.12.011. PMID 16414182. 
  • Polanco JC, Koopman P (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. 
  • Hawkins JR, Taylor A, Berta P, et al. (1992). "Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal.". Hum. Genet. 88 (4): 471-4. doi:10.1007/BF00215684. PMID 1339396. 
  • Hawkins JR, Taylor A, Goodfellow PN, et al. (1992). "Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis.". Am. J. Hum. Genet. 51 (5): 979-84. PMID 1415266. 
  • Ferrari S, Harley VR, Pontiggia A, et al. (1992). "SRY, like HMG1, recognizes sharp angles in DNA.". EMBO J. 11 (12): 4497-506. PMID 1425584. 
  • Jäger RJ, Harley VR, Pfeiffer RA, et al. (1993). "A familial mutation in the testis-determining gene SRY shared by both sexes.". Hum. Genet. 90 (4): 350-5. PMID 1483689. 
  • Vilain E, McElreavey K, Jaubert F, et al. (1992). "Familial case with sequence variant in the testis-determining region associated with two sex phenotypes.". Am. J. Hum. Genet. 50 (5): 1008-11. PMID 1570829. 
  • Müller J, Schwartz M, Skakkebaek NE (1992). "Analysis of the sex-determining region of the Y chromosome (SRY) in sex reversed patients: point-mutation in SRY causing sex-reversion in a 46,XY female.". J. Clin. Endocrinol. Metab. 75 (1): 331-3. doi:10.1210/jc.75.1.331. PMID 1619028. 
  • McElreavey KD, Vilain E, Boucekkine C, et al. (1992). "XY sex reversal associated with a nonsense mutation in SRY.". Genomics 13 (3): 838-40. doi:10.1016/0888-7543(92)90164-N. PMID 1639410. 
  • Sinclair AH, Berta P, Palmer MS, et al. (1990). "A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif.". Nature 346 (6281): 240-4. doi:10.1038/346240a0. PMID 1695712. 
  • Berkovitz GD, Fechner PY, Zacur HW, et al. (1991). "Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation.". Medicine (Baltimore) 70 (6): 375-83. PMID 1956279. 
  • Berta P, Hawkins JR, Sinclair AH, et al. (1991). "Genetic evidence equating SRY and the testis-determining factor.". Nature 348 (6300): 448-50. doi:10.1038/348448A0. PMID 2247149. 
  • Jäger RJ, Anvret M, Hall K, Scherer G (1991). "A human XY female with a frame shift mutation in the candidate testis-determining gene SRY.". Nature 348 (6300): 452-4. doi:10.1038/348452a0. PMID 2247151. 
  • Ellis NA, Goodfellow PJ, Pym B, et al. (1989). "The pseudoautosomal boundary in man is defined by an Alu repeat sequence inserted on the Y chromosome.". Nature 337 (6202): 81-4. doi:10.1038/337081a0. PMID 2909893. 
  • Whitfield LS, Hawkins TL, Goodfellow PN, Sulston J (1995). "41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome.". Genomics 27 (2): 306-11. doi:10.1006/geno.1995.1047. PMID 7557997. 

[edit] External links

v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)
ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • Neurogenins • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Scleraxis • TAL1 • Twist • USF1
(1.3) bHLH-ZIP
MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4
GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3)
(2.3) Cys2His2
ATBF1 • BCL(6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF: 1, 2, TFIIH: 1, 2, 4, 2I, 3A, 3C1, 3C2) • GFI1 • GLI-Krüppel family (1, 2, 3, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 4, 5, 6, 9, 10, 11, 12, 13) • MTF1 • MYT1 • OSR1 • Sp1 • zinc finger ((3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 451, 452, 471, 593, 638, 649, 655) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6
(2.5) Alternating composition
AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B
(3) Helix-turn-helix
domains
ARX • CDX (1, 2) • CRX • CUTL1 • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-5, 3-1) • PHF (3, 6, 10, 17) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) • OTX (1, 2) • PDX1
(3.2) Paired box
PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, , O3A, O4, P1, P2, P3)
HSF (1, 2, 4)
(3.5) Tryptophan clusters
ELF (4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(3.6) TEA domain
transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region
NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)
(4.2) STAT
STAT (1, 2, 3, 4, 5, 6)
(4.3) p53
(4.4) MADS box
Mef2 (A, B, C, D) • SRF
HNF (1A, 1B) • LEF1 • SOX (2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 15, 18) • SRY • SSRP1
(4.10) Cold-shock domain
(4.11) Runt
(0) Other
transcription factors
(0.2) HMGI(Y)
HMGA (1, 2) • HBP1
Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-related factors
Apetala 2 • EREBP • B3
(0.6) Miscellaneous
ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFI (A, B, C, X) • NFY (A, B, C) • Rho/Sigma • R-SMAD