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PMID: 18660847 Published · ppublish English Journal Article

The Human Pseudoautosomal Region (PAR): Origin, Function and Future.

Current genomics ·Vol. 8 ·No. 2 ·2007-04-00 ·Pages 129-36

Helena Mangs A, Morris BJ

Abstract

The pseudoautosomal regions (PAR1 and PAR2) of the human X and Y chromosomes pair and recombine during meiosis. Thus genes in this region are not inherited in a strictly sex-linked fashion. PAR1 is located at the terminal region of the short arms and PAR2 at the tips of the long arms of these chromosomes. To date, 24 genes have been assigned to the PAR1 region. Half of these have a known function. In contrast, so far only 4 genes have been discovered in the PAR2 region. Deletion of the PAR1 region results in failure of pairing and male sterility. The gene SHOX (short stature homeobox-containing) resides in PAR1. SHOX haploinsufficiency contributes to certain features in Turner syndrome as well as the characteristics of Leri-Weill dyschondrosteosis. Only two of the human PAR1 genes have mouse homologues. These do not, however, reside in the mouse PAR1 region but are autosomal. The PAR regions seem to be relics of differential additions, losses, rearrangements and degradation of the X and Y chromosome in different mammalian lineages. Marsupials have three homologues of human PAR1 genes in their autosomes, although, in contrast to mouse, do not have a PAR region at all. The disappearance of PAR from other species seems likely and this region will only be rescued by the addition of genes to both X and Y, as has occurred already in lemmings. The present review summarizes the current understanding of the evolution of PAR and provides up-to-date information about individual genes residing in this region.

Keywords
PAR Pseudoautosomal region SHOX XE7 sex chromosomes
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Helena Mangs A
Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, The University of Sydney, NSW 2006, Australia.
Morris Brian J
References (94)
94 references, click to expand
  1. CD99 signals caspase-independent T cell death.
    J Immunol. 2001 Apr 15;166(8):4931-42 PMID: 11290771
  2. XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265.
    Nucleic Acids Res. 2006;34(17):4976-86 PMID: 16982639
  3. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome.
    Nat Genet. 1997 May;16(1):54-63 PMID: 9140395
  4. Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial.
    J Clin Endocrinol Metab. 2007 Jan;92(1):219-28 PMID: 17047016
  5. The Y chromosome as a target for acquired and amplified genetic material in evolution.
    Bioessays. 2005 Dec;27(12):1256-62 PMID: 16299764
  6. Sex chromosomes: evolution of the weird and wonderful.
    Curr Biol. 2005 Feb 22;15(4):R129-31 PMID: 15723783
  7. A human pseudoautosomal gene, ADP/ATP translocase, escapes X-inactivation whereas a homologue on Xq is subject to X-inactivation.
    Nat Genet. 1993 Jan;3(1):82-7 PMID: 8490661
  8. Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome.
    J Clin Endocrinol Metab. 1999 Dec;84(12):4613-21 PMID: 10599728
  9. Cloning and expression of the mouse pseudoautosomal steroid sulphatase gene (Sts).
    Nat Genet. 1996 May;13(1):83-6 PMID: 8673109
  10. Role of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in the development of an acute neutrophil inflammatory response in mice.
    Blood. 1996 Nov 15;88(10):3755-64 PMID: 8916939
  11. The alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling.
    J Biol Chem. 2006 Aug 4;281(31):22421-22426 PMID: 16760463
  12. The degeneration of Y chromosomes.
    Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1563-72 PMID: 11127901
  13. Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain.
    Trends Biochem Sci. 2001 Jul;26(7):407-9 PMID: 11440841
  14. Functional expression of IL-9 receptor by human neutrophils from asthmatic donors: role in IL-8 release.
    J Immunol. 2001 Feb 15;166(4):2768-74 PMID: 11160343
  15. Cloning and sequencing of a trophoblast-endothelial-activated lymphocyte surface protein: cDNA sequence and genomic structure.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10425-9 PMID: 1438229
  16. Identification of a novel type I cytokine receptor CRL2 preferentially expressed by human dendritic cells and activated monocytes.
    Biochem Biophys Res Commun. 2001 Mar 9;281(4):878-83 PMID: 11237741
  17. Phenotypic variation and genetic heterogeneity in Léri-Weill syndrome.
    Eur J Hum Genet. 2000 Jan;8(1):54-62 PMID: 10713888
  18. Granulocyte-macrophage colony-stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos.
    Biol Reprod. 2002 Dec;67(6):1817-23 PMID: 12444058
  19. Asthma and bronchial hyperresponsiveness linked to the XY long arm pseudoautosomal region.
    Genomics. 1998 Sep 1;52(2):233-5 PMID: 9782093
  20. High incidence of SHOX anomalies in individuals with short stature.
    J Med Genet. 2006 Sep;43(9):735-9 PMID: 16597678
  21. Isolation and characterization of the human interleukin-9 receptor gene.
    Blood. 1994 Jun 1;83(11):3199-205 PMID: 8193355
  22. SHOX point mutations in dyschondrosteosis.
    J Med Genet. 2001 May;38(5):323 PMID: 11403039
  23. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.
    J Immunol. 2001 Jul 1;167(1):336-43 PMID: 11418668
  24. Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone.
    J Clin Endocrinol Metab. 2000 Jan;85(1):245-9 PMID: 10634394
  25. Differentially regulated and evolved genes in the fully sequenced Xq/Yq pseudoautosomal region.
    Hum Mol Genet. 2000 Feb 12;9(3):395-401 PMID: 10655549
  26. X-linkage of steroid sulphatase in the mouse is evidence for a functional Y-linked allele.
    Nature. 1985 May 16-22;315(6016):226-7 PMID: 3858674
  27. Characterization of the murine orthologue of a novel human subtelomeric multigene family.
    Cytogenet Cell Genet. 2001;94(1-2):98-100 PMID: 11701968
  28. Immunoreactivity of CD99 in invasive malignant melanoma.
    J Cutan Pathol. 2006 Oct;33(10):663-6 PMID: 17026517
  29. Differential divergence of three human pseudoautosomal genes and their mouse homologs: implications for sex chromosome evolution.
    Genome Res. 2001 Dec;11(12):2095-100 PMID: 11731500
  30. PHOG, a candidate gene for involvement in the short stature of Turner syndrome.
    Hum Mol Genet. 1997 Aug;6(8):1341-7 PMID: 9259282
  31. The E2 antigen, a 32 kd glycoprotein involved in T-cell adhesion processes, is the MIC2 gene product.
    EMBO J. 1989 Nov;8(11):3253-9 PMID: 2479542
  32. The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes.
    Hum Mol Genet. 1994 May;3(5):771-8 PMID: 8081364
  33. Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay.
    J Hum Genet. 2007;52(1):21-27 PMID: 17091221
  34. Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark.
    Birth Defects Orig Artic Ser. 1990;26(4):209-23 PMID: 2090319
  35. Complex events in the evolution of the human pseudoautosomal region 2 (PAR2).
    Genome Res. 2003 Feb;13(2):281-6 PMID: 12566406
  36. SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity.
    J Clin Endocrinol Metab. 2004 Sep;89(9):4403-8 PMID: 15356038
  37. Complete SHOX deficiency causes Langer mesomelic dysplasia.
    Am J Med Genet. 2002 Jun 15;110(2):158-63 PMID: 12116254
  38. Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
    Genome Res. 2006 Jan;16(1):55-65 PMID: 16344560
  39. Deficiency of X and Y chromosomal pairing at meiotic prophase in spermatocytes of sterile interspecific hybrids between laboratory mice (Mus domesticus) and Mus spretus.
    Chromosoma. 1992 Jun;101(8):483-92 PMID: 1424992
  40. A novel pseudoautosomal human gene encodes a putative protein similar to Ac-like transposases.
    Hum Mol Genet. 1999 Jan;8(1):61-7 PMID: 9887332
  41. CSF2RA, ANT3, and STS are autosomal in marsupials: implications for the origin of the pseudoautosomal region of mammalian sex chromosomes.
    Mamm Genome. 1998 May;9(5):373-6 PMID: 9545494
  42. Loss of the Y chromosomal PAR2-region in four familial cases of satellited Y chromosomes (Yqs).
    Chromosome Res. 2001;9(3):215-22 PMID: 11330396
  43. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor.
    EMBO J. 1989 Dec 1;8(12):3667-76 PMID: 2555171
  44. Localization of the hydroxyindole-O-methyltransferase gene to the pseudoautosomal region: implications for mapping of psychiatric disorders.
    Hum Mol Genet. 1993 Feb;2(2):127-31 PMID: 8098975
  45. Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and bipolar affective disorder.
    Am J Med Genet. 2002 Jan 8;114(1):74-8 PMID: 11840509
  46. CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.
    J Immunol. 1997 Sep 1;159(5):2250-8 PMID: 9278313
  47. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9655-9 PMID: 1702217
  48. A functional isoform of the human granulocyte/macrophage colony-stimulating factor receptor has an unusual cytoplasmic domain.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7744-8 PMID: 1715577
  49. IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells.
    J Immunol. 2004 Aug 15;173(4):2771-9 PMID: 15294996
  50. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: meiotic studies in a man with a deletion of distal Xp.
    Am J Hum Genet. 1992 Sep;51(3):526-33 PMID: 1496984
  51. Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp.
    Nat Genet. 1994 Apr;6(4):394-400 PMID: 8054981
  52. A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis.
    Am J Hum Genet. 2005 Oct;77(4):533-44 PMID: 16175500
  53. The evolution of chromosomal sex determination.
    Novartis Found Symp. 2002;244:207-19; discussion 220-4, 253-7 PMID: 11990792
  54. Sex specific protective effects of interleukin-9 receptor haplotypes on childhood wheezing and sensitisation.
    J Med Genet. 2004 Dec;41(12):e123 PMID: 15591265
  55. Identification of a major recombination hotspot in patients with short stature and SHOX deficiency.
    Am J Hum Genet. 2005 Jul;77(1):89-96 PMID: 15931595
  56. Constitutive mutants of the GM-CSF receptor reveal multiple pathways leading to myeloid cell survival, proliferation, and granulocyte-macrophage differentiation.
    Blood. 2004 Jan 15;103(2):507-16 PMID: 14504109
  57. The DNA sequence of the human X chromosome.
    Nature. 2005 Mar 17;434(7031):325-37 PMID: 15772651
  58. Sex chromosome specialization and degeneration in mammals.
    Cell. 2006 Mar 10;124(5):901-14 PMID: 16530039
  59. Recombination and allelic association in the Xq/Yq homology region.
    Hum Mol Genet. 1995 Nov;4(11):2013-6 PMID: 8589676
  60. IL-4-induced upregulation of adenine nucleotide translocase 3 and its role in Th cell survival from apoptosis.
    Cell Immunol. 2006 May;241(1):14-25 PMID: 16930576
  61. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin.
    Nat Immunol. 2000 Jul;1(1):59-64 PMID: 10881176
  62. Structure and expression of the human pseudoautosomal gene XE7.
    Hum Mol Genet. 1992 Dec;1(9):691-6 PMID: 1302606
  63. Fertility in mice requires X-Y pairing and a Y-chromosomal "spermiogenesis" gene mapping to the long arm.
    Cell. 1992 Oct 30;71(3):391-8 PMID: 1423603
  64. A novel pseudoautosomal gene encoding a putative GTP-binding protein resides in the vicinity of the Xp/Yp telomere.
    Hum Mol Genet. 1998 Mar;7(3):407-14 PMID: 9466997
  65. Genes located in and near the human pseudoautosomal region are located in the X-Y pairing region in dog and sheep.
    Chromosome Res. 1997 Aug;5(5):301-6 PMID: 9292234
  66. A gene spans the pseudoautosomal boundary in mice.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12030-5 PMID: 9342357
  67. PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of Léri-Weill dyschondrosteosis (LWD) probands.
    Hum Mutat. 2006 Oct;27(10):1062 PMID: 16941489
  68. PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
    Mol Cell Biol. 2000 Feb;20(3):1021-9 PMID: 10629059
  69. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
    Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903 PMID: 12477932
  70. The IL9R region contribution in asthma is supported by genetic association in an isolated population.
    Eur J Hum Genet. 2000 Oct;8(10):788-92 PMID: 11039580
  71. Cytogenetics of collared lemmings (Dicrostonyx groenlandicus). I. Meiotic behavior and evolution of the neo-XY sex-chromosome system.
    Cytogenet Cell Genet. 1997;79(3-4):288-92 PMID: 9605875
  72. A cytokine receptor gene cluster in the X-Y pseudoautosomal region?
    Blood. 1993 Jul 1;82(1):22-8 PMID: 8100720
  73. PBDX is the XG blood group gene.
    Nat Genet. 1994 Nov;8(3):285-90 PMID: 7533029
  74. Gene duplications as a recurrent theme in the evolution of the human pseudoautosomal region 1: isolation of the gene ASMTL.
    Hum Mol Genet. 1998 Oct;7(11):1771-8 PMID: 9736779
  75. The pseudoautosomal regions of the human sex chromosomes.
    Hum Genet. 1993 Oct;92(4):315-24 PMID: 8225310
  76. Identification and molecular cloning of a soluble human granulocyte-macrophage colony-stimulating factor receptor.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8203-7 PMID: 1832774
  77. Directed isolation of human genes that escape X inactivation.
    Somat Cell Mol Genet. 1992 May;18(3):259-68 PMID: 1496421
  78. Analysis of the pseudoautosomal X-linked gene SYBL1in bipolar affective disorder: description of a new candidate allele for psychiatric disorders.
    Am J Med Genet. 2000 Jun 12;96(3):317-23 PMID: 10898908
  79. A role for TSLP in the development of inflammation in an asthma model.
    J Exp Med. 2005 Sep 19;202(6):829-39 PMID: 16172260
  80. A human pseudoautosomal gene encodes the ANT3 ADP/ATP translocase and escapes X-inactivation.
    Genomics. 1993 Apr;16(1):26-33 PMID: 8486369
  81. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).
    Nat Genet. 1998 May;19(1):67-9 PMID: 9590292
  82. MIC2: a human pseudoautosomal gene.
    Philos Trans R Soc Lond B Biol Sci. 1988 Dec 1;322(1208):145-54 PMID: 2907798
  83. Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males.
    J Med Genet. 2004 Oct;41(10):736-42 PMID: 15466006
  84. The origin and evolution of the pseudoautosomal regions of human sex chromosomes.
    Hum Mol Genet. 1998 Dec;7(13):1991-6 PMID: 9817914
  85. Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency.
    J Med Genet. 2007 May;44(5):306-13 PMID: 17182655
  86. Interleukin-9 receptor expression in asthmatic airways In vivo.
    Lung. 2000;178(3):149-60 PMID: 10871433
  87. A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes.
    Nature. 1986 Jan 23-29;319(6051):291-5 PMID: 3941746
  88. Identification of a second pseudoautosomal region near the Xq and Yq telomeres.
    Science. 1992 Dec 11;258(5089):1784-7 PMID: 1465614
  89. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors.
    Cell. 1991 Sep 20;66(6):1165-74 PMID: 1833064
  90. The evolution of sex chromosomes.
    Science. 1991 Mar 1;251(4997):1030-3 PMID: 1998119
  91. Large-scale proteomic analysis of the human spliceosome.
    Genome Res. 2002 Aug;12(8):1231-45 PMID: 12176931
  92. Expression cloning of the murine and human interleukin 9 receptor cDNAs.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5690-4 PMID: 1376929
  93. The human FXY gene is located within Xp22.3: implications for evolution of the mammalian X chromosome.
    Hum Mol Genet. 1998 Feb;7(2):299-305 PMID: 9425238
  94. Phenotypes Associated with SHOX Deficiency.
    J Clin Endocrinol Metab. 2001 Dec;86(12):5674-80 PMID: 11739418
Article Info
Journal
Current genomics
Abbr.
Curr Genomics
ISSN
1389-2029
DOI
10.2174/138920207780368141
Published
2007-04-00
Pages
129-36
Language
English
Region
United Arab Emirates
NLM ID
100960527
PMCID
PMC2435358
External Links
PubMed source DOI: 10.2174/138920207780368141 PMC Full Text View journal details
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