Functional & Integrative Genomics

, Volume 13, Issue 3, pp 285–293 | Cite as

Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome

  • Avinash M. Veerappa
  • Prakash Padakannaya
  • Nallur B. Ramachandra
Original Paper

Abstract

A 3.5-Mb region of the X chromosome underwent duplication and transposition to the Y chromosome ~5–6 Mya. This X-transposed-region (XTR) originated at Xq21.3 and was inserted at Yp11.2. The two locations have 98.78 % homology and a high concentration of tandem repeats. In whole-genome scans of ten large families with dyslexic members, we identified transposed blocks comprising >102 kb of the Yp11.2 region in its homologous region at Xq21.3 in three females from three different families. Although recombination is known to be limited only to the pseudoautosomal regions (PARs) of the X and Y chromosomes, we report allelic unequal recombination between the XTR region Yp11.2 and Xq21.3, indicating the presence of a new PAR, which we named PAR3. This PAR3 region was also found in 2 % of the general population. An additional layer of justification could be provided from six other dyslexic cases which harbored duplications and deletions in the same Xq21.3 and Yp11.2 regions through allelic unequal recombination.

Keywords

PAR1 PAR2 CNV X-transposed region Yp11.2 Xq21.3 PAR3 

Supplementary material

10142_2013_323_MOESM1_ESM.jpg (913 kb)
Supplementary Fig. 1Illustration of three pedigrees under study. a, b and c are the pedigrees of three dyslexic families showing the recombined blocks of Yp11.2 in one of the X-chromosome Xq21.3 region (a-IV-2; b-III-11 and c-III-6). The arrows indicate the probands which shows the duplicated and deleted blocks found in Xq21.3/PCDH11X/TGIF2LX region (a-V-2 and b-III-10). (JPEG 912 kb)
10142_2013_323_MOESM2_ESM.jpg (178 kb)
Supplementary Fig. 2(JPEG 177 kb)

References

  1. Affymetrix Inc. (2005) Technical note: guide to probe logarithmic intensity error (PLIER) estimationGoogle Scholar
  2. Affymetrix Inc. (2007) White Paper: BRLMM-P: a genotype calling method for the SNP array 5.0Google Scholar
  3. Affymetrix Inc. (2008) User manual: Genotyping Console™ Software 2.1Google Scholar
  4. Affymetrix Inc. (2009) Data sheet: Genome Wide Human SNP Array 6.0Google Scholar
  5. Benyamin B, Visscher PM, McRae A (2009) Family-based genome-wide association studies. Pharmacogenomics 10:181–190PubMedCrossRefGoogle Scholar
  6. Charlesworth B (1991) The evolution of sex chromosomes. Science 4997:1030–1033CrossRefGoogle Scholar
  7. De Bonis ML, Cerase A, Matarazzo MR, Ferraro M, Strazzullo M et al (2006) Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications. Hum Mol Genet 15:1123–1132PubMedCrossRefGoogle Scholar
  8. Flaquer A, Rappold GA, Wienker TF, Fischer C (2008) The human pseudoautosomal regions: a review for genetic epidemiologists. Eur J Hum Genet 16:771–779PubMedCrossRefGoogle Scholar
  9. Giouzeli M, Williams NA, Lonie LJ, DeLisi LE, Crow TJ (2004) ProtocadherinX/Y, a candidate gene-pair for schizophrenia and schizoaffective disorder: a DHPLC investigation of genomic sequences. Am J Med Genet Part B 129B:1–9PubMedCrossRefGoogle Scholar
  10. Jobling MA, Lo LC, Turner DJ, Bowden GR, Lee AC et al (2007) Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y. Hum Mol Genet 16:307–316PubMedCrossRefGoogle Scholar
  11. Lambson B, Affara NA, Mitchell M, Ferguson-Smith MA (1992) Evolution of DNA sequence homologies between the sex chromosomes in primate species. Genomics 14:1032–1040PubMedCrossRefGoogle Scholar
  12. Lima RD, Iamanda CF, Silva LR, Mello MP, Maciel-Guerra AT (2008) An illustrative case of Leri–Weill dyschondrosteosis. Genet Mol Biol 31:839–842CrossRefGoogle Scholar
  13. Lopes AM, Ross N, Close J, Dagnall A, Amorim A et al (2006) Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain. Hum Genet 119:267–275PubMedCrossRefGoogle Scholar
  14. Mangs AH, Morris BJ (2007) The human pseudoautosomal region (PAR): origin, function and future. Curr Genomics 8:129–136CrossRefGoogle Scholar
  15. Ohno S (1967) Sex chromosomes and sex-linked genes. Springer Books, BerlinCrossRefGoogle Scholar
  16. Page DC, Harper ME, Love J, Botstein D (1984) Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature 311:119–123PubMedCrossRefGoogle Scholar
  17. Rappold GA, Klink A, Weiss B, Fischer C (1994) Double crossover in the human Xp/Yp pseudoautosomal region and its bearing on interference. Hum Mol Genet 3(8):1337–1340PubMedCrossRefGoogle Scholar
  18. Ried K, Rao E, Schiebel K, Rappold GA (1998) Gene duplications as a recurrent theme in the evolution of the human pseudoautosomal region 1: isolation of the gene ASMTL. Hum Mol Gene 7:1771–1778CrossRefGoogle Scholar
  19. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K et al (2005) The DNA sequence of the human X chromosome. Nature 434:325–337PubMedCrossRefGoogle Scholar
  20. Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS et al (2003) Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423:873–876PubMedCrossRefGoogle Scholar
  21. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L et al (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423:825–837PubMedCrossRefGoogle Scholar
  22. SVS Golden Helix (2010) SVS Golden Helix testing manual. http://www.goldenhelix.com/SNP_Variation/tutorials/snp-with-svs7/introduction.html
  23. Weissenbach J, Levilliers J, Petit C, Rouyer F, and Simmler M-C (1987) Normal and abnormal interchanges between the human X and Y chromosomes. Development 101(Suppl):67–74Google Scholar
  24. Williams NA, Close J, Giouzeli M, Crow TJ (2006) Accelerated evolution of Protocadherin 11X/Y: a candidate gene-pair for cerebral asymmetry and language. Am J Med Genet Part B 141B:1–11CrossRefGoogle Scholar
  25. Zarate YA, Dwivedi A, Bartel FO, Corning K, DuPont BR (2011) 47, XY, +der(Y), t(X;Y) (p21.1;p11.2): a unique case of XY sex reversal. Am J Med Genet Part A 155:386–391CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Avinash M. Veerappa
    • 1
  • Prakash Padakannaya
    • 2
  • Nallur B. Ramachandra
    • 1
  1. 1.Genomics Laboratory, DOS in ZoologyUniversity of MysoreMysore-06India
  2. 2.DOS in PsychologyUniversity of MysoreMysore-06India

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