• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Mar 25, 1993; 21(6): 1409–1417.
PMCID: PMC309326

Duplicated KOX zinc finger gene clusters flank the centromere of human chromosome 10: evidence for a pericentric inversion during primate evolution.


Two related zinc finger (ZNF) gene clusters from the pericentromeric region of human chromosome 10, defined by cDNAs of the KOX series, have been cloned in yeast artificial chromosomes (YACs). The two clusters evolved by duplication of an ancestral gene cluster before the divergence of the human and great ape lineages. Included in cluster A are the ZNF gene sequences ZNF11A, ZNF33A, and ZNF37A, while cluster B comprises the related sequences ZNF11B, ZNF33B and ZNF37B. Genes from both clusters are expressed: cDNAs KOX2, KOX31 and KOX21 derive from ZNF11B, ZNF33A and ZNF37A, respectively. Further YACs have been isolated which link ZNF11A and ZNF33A to another gene, ZNF25, defined by cDNA clone KOX19. Therefore ZNF25 also forms part of cluster A, but has no counterpart in cluster B. Surprisingly, the KOX ZNF gene clusters are located on opposite sides of the centromere: cluster A maps to 10p11.2, while cluster B is in 10q11.2. This suggests the occurrence during primate evolution of a previously undescribed pericentric inversion subsequent to the cluster duplication. The evolution of this subset of KOX ZNF genes has therefore involved three types of genetic event: local gene duplication, gene cluster duplication, and chromosome rearrangement.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Nakamura Y, Mathew CG, Sobol H, Easton DF, Telenius H, Bragg T, Chin K, Clark J, Jones C, Lenoir GM, et al. Linked markers flanking the gene for multiple endocrine neoplasia type 2A. Genomics. 1989 Aug;5(2):199–203. [PubMed]
  • Wu JS, Carson NL, Myers S, Pakstis AJ, Kidd JR, Castiglione CM, Anderson L, Hoyle LS, Genel M, Verdy M, et al. The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10. Am J Hum Genet. 1990 Mar;46(3):624–630. [PMC free article] [PubMed]
  • Rousseau-Merck MF, Tunnacliffe A, Berger R, Ponder BA, Thiesen HJ. A cluster of expressed zinc finger protein genes in the pericentromeric region of human chromosome 10. Genomics. 1992 Jul;13(3):845–848. [PubMed]
  • Brown RS, Sander C, Argos P. The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett. 1985 Jul 8;186(2):271–274. [PubMed]
  • Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. [PMC free article] [PubMed]
  • Bellefroid EJ, Lecocq PJ, Benhida A, Poncelet DA, Belayew A, Martial JA. The human genome contains hundreds of genes coding for finger proteins of the Krüppel type. DNA. 1989 Jul-Aug;8(6):377–387. [PubMed]
  • Thiesen HJ. Multiple genes encoding zinc finger domains are expressed in human T cells. New Biol. 1990 Apr;2(4):363–374. [PubMed]
  • Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L, et al. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991 Oct 18;67(2):437–447. [PubMed]
  • Vortkamp A, Gessler M, Grzeschik KH. GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. Nature. 1991 Aug 8;352(6335):539–540. [PubMed]
  • Huebner K, Druck T, Croce CM, Thiesen HJ. Twenty-seven nonoverlapping zinc finger cDNAs from human T cells map to nine different chromosomes with apparent clustering. Am J Hum Genet. 1991 Apr;48(4):726–740. [PMC free article] [PubMed]
  • Lichter P, Bray P, Ried T, Dawid IB, Ward DC. Clustering of C2-H2 zinc finger motif sequences within telomeric and fragile site regions of human chromosomes. Genomics. 1992 Aug;13(4):999–1007. [PubMed]
  • Hoovers JM, Mannens M, John R, Bliek J, van Heyningen V, Porteous DJ, Leschot NJ, Westerveld A, Little PF. High-resolution localization of 69 potential human zinc finger protein genes: a number are clustered. Genomics. 1992 Feb;12(2):254–263. [PubMed]
  • Brownstein BH, Silverman GA, Little RD, Burke DT, Korsmeyer SJ, Schlessinger D, Olson MV. Isolation of single-copy human genes from a library of yeast artificial chromosome clones. Science. 1989 Jun 16;244(4910):1348–1351. [PubMed]
  • Burke DT, Carle GF, Olson MV. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science. 1987 May 15;236(4803):806–812. [PubMed]
  • Schwartz DC, Cantor CR. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984 May;37(1):67–75. [PubMed]
  • Radice P, Tunnacliffe A. Distinct breakpoints in band 11q23 of the t(4;11) and t(11;14) associated with leukocyte malignancy. Genes Chromosomes Cancer. 1992 Jul;5(1):50–56. [PubMed]
  • Nelson DL, Ledbetter SA, Corbo L, Victoria MF, Ramírez-Solis R, Webster TD, Ledbetter DH, Caskey CT. Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6686–6690. [PMC free article] [PubMed]
  • Hultman T, Ståhl S, Hornes E, Uhlén M. Direct solid phase sequencing of genomic and plasmid DNA using magnetic beads as solid support. Nucleic Acids Res. 1989 Jul 11;17(13):4937–4946. [PMC free article] [PubMed]
  • Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980 Dec;16(2):111–120. [PubMed]
  • Mathew CG, Wakeling W, Jones E, Easton D, Fisher R, Strong C, Smith B, Chin K, Little P, Nakamura Y, et al. Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping. Ann Hum Genet. 1990 May;54(Pt 2):121–129. [PubMed]
  • Trask BJ, van den Engh G, Christensen M, Massa HF, Gray JW, Van Dilla M. Characterization of somatic cell hybrids by bivariate flow karyotyping and fluorescence in situ hybridization. Somat Cell Mol Genet. 1991 Mar;17(2):117–136. [PubMed]
  • Kao FT, Puck TT. Induction and isolation of auxotrophic mutants in mammalian cells. Methods Cell Biol. 1974;8(0):23–39. [PubMed]
  • Decker RA, Moore J, Ponder B, Weber JL. Linkage mapping of human chromosome 10 microsatellite polymorphisms. Genomics. 1992 Mar;12(3):604–606. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Cremer T, Lichter P, Borden J, Ward DC, Manuelidis L. Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum Genet. 1988 Nov;80(3):235–246. [PubMed]
  • Suijkerbuijk RF, Matthopoulos D, Kearney L, Monard S, Dhut S, Cotter FE, Herbergs J, van Kessel AG, Young BD. Fluorescent in situ identification of human marker chromosomes using flow sorting and Alu element-mediated PCR. Genomics. 1992 Jun;13(2):355–362. [PubMed]
  • Pinkel D, Straume T, Gray JW. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. [PMC free article] [PubMed]
  • Fan YS, Davis LM, Shows TB. Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6223–6227. [PMC free article] [PubMed]
  • Sibley CG, Ahlquist JE. DNA hybridization evidence of hominoid phylogeny: results from an expanded data set. J Mol Evol. 1987;26(1-2):99–121. [PubMed]
  • Jackson MS, Mole SE, Ponder BA. Characterisation of a boundary between satellite III and alphoid sequences on human chromosome 10. Nucleic Acids Res. 1992 Sep 25;20(18):4781–4787. [PMC free article] [PubMed]
  • Harrison SC. A structural taxonomy of DNA-binding domains. Nature. 1991 Oct 24;353(6346):715–719. [PubMed]
  • Pankratz MJ, Jäckle H. Making stripes in the Drosophila embryo. Trends Genet. 1990 Sep;6(9):287–292. [PubMed]
  • Kasai Y, Nambu JR, Lieberman PM, Crews ST. Dorsal-ventral patterning in Drosophila: DNA binding of snail protein to the single-minded gene. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3414–3418. [PMC free article] [PubMed]
  • Chowdhury K, Deutsch U, Gruss P. A multigene family encoding several "finger" structures is present and differentially active in mammalian genomes. Cell. 1987 Mar 13;48(5):771–778. [PubMed]
  • Stanojević D, Hoey T, Levine M. Sequence-specific DNA-binding activities of the gap proteins encoded by hunchback and Krüppel in Drosophila. Nature. 1989 Sep 28;341(6240):331–335. [PubMed]
  • Hsu T, Gogos JA, Kirsh SA, Kafatos FC. Multiple zinc finger forms resulting from developmentally regulated alternative splicing of a transcription factor gene. Science. 1992 Sep 25;257(5078):1946–1950. [PubMed]
  • Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. [PubMed]
  • Hoch M, Gerwin N, Taubert H, Jäckle H. Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. Science. 1992 Apr 3;256(5053):94–97. [PubMed]
  • Drummond IA, Madden SL, Rohwer-Nutter P, Bell GI, Sukhatme VP, Rauscher FJ., 3rd Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science. 1992 Jul 31;257(5070):674–678. [PubMed]
  • Seite P, Huebner K, Rousseau-Merck MF, Berger R, Thiesen HJ. Two human genes encoding zinc finger proteins, ZNF 12 (KOX 3) and ZNF 26 (KOX 20), map to chromosome 7p22-p21 and 12q24.33, respectively. Hum Genet. 1991 Apr;86(6):585–590. [PubMed]
  • Williams TM, Montoya G, Wu Y, Eddy RL, Byers MG, Shows TB. The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2. Genomics. 1992 Sep;14(1):194–196. [PubMed]
  • Crossley PH, Little PF. A cluster of related zinc finger protein genes is deleted in the mouse embryonic lethal mutation tw18. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7923–7927. [PMC free article] [PubMed]
  • Grosveld F, van Assendelft GB, Greaves DR, Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. [PubMed]
  • Huber C, Thiebe R, Hameister H, Smola H, Lötscher E, Zachau HG. A human immunoglobulin kappa orphon without sequence defects may be the product of a pericentric inversion. Nucleic Acids Res. 1990 Jun 25;18(12):3475–3478. [PMC free article] [PubMed]
  • Zimmer FJ, Hameister H, Schek H, Zachau HG. Transposition of human immunoglobulin V kappa genes within the same chromosome and the mechanism of their amplification. EMBO J. 1990 May;9(5):1535–1542. [PMC free article] [PubMed]
  • Yunis JJ, Prakash O. The origin of man: a chromosomal pictorial legacy. Science. 1982 Mar 19;215(4539):1525–1530. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...