Elsevier

Genomics

Volume 79, Issue 2, February 2002, Pages 210-217
Genomics

Regular Article
Genomic Analysis of Human Chromosome 10q and 4q Telomeres Suggests a Common Origin

https://doi.org/10.1006/geno.2002.6690Get rights and content

Abstract

The subtelomeric region of human chromosome 4q contains the locus for facioscapulohumeral muscular dystrophy (FSHD). The FSHD mutation is a deletion within an array of 3.3-kb tandem repeats (D4Z4). The disease mechanism is unknown but is postulated to involve position effect. A closely related 3.3-kb array on chromosome 10qter, in contrast, is not associated with a disease phenotype. We show here that the 4q homology on chromosome 10 is not confined to the 3.3-kb repeats but extends both proximally (42 kb) and distally to include the telomere. We have also identified the most distal expressed gene on 10q known so far, mapping only 96 kb from the 3.3-kb repeat array. A 4q variant has also been identified; there is 92%nucleotide identity between the two 4q forms, 4qA and 4qB. The 4qter and 10qter forms show homology to other chromosome ends, including 4p, 21q, and 22q, and these regions may represent a relatively common subtelomeric domain.

References (42)

  • P.K. Grewal et al.

    Recent amplification of the human FRG1 gene during primate evolution

    Gene

    (1999)
  • J. Gabriels

    Nucleotide sequencing of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element

    Gene

    (1999)
  • J. Flint

    Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

    Hum. Mol. Genet.

    (1997)
  • M. Hattori

    The DNA sequence of human chromosome 21

    Nature

    (2000)
  • R.J. Daniels

    Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16

    Hum. Mol. Genet.

    (2001)
  • S. Saccone et al.

    The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes

    Proc. Natl. Acad. Sci. USA

    (1992)
  • J.M. Craig et al.

    Chromosome bands–flavours to savour

    Bioessays

    (1993)
  • J. Flint

    The relationship between chromosome structure and function at a human telomeric region

    Nat. Genet.

    (1997)
  • J. Flint

    The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation

    Nat. Genet.

    (1995)
  • C. Wijmenga

    Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy

    Nat. Genet.

    (1992)
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    • The evolution of DUX4 gene regulation and its implication for facioscapulohumeral muscular dystrophy

      2022, Biochimica et Biophysica Acta - Molecular Basis of Disease
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      Yet, the difficulty in detecting DUX4 expression in FSHD muscle caused much skepticism in the gain-of-function model of DUX4 causing FSHD. The presence of a nearly identical D4Z4 repeat array containing DUX4 on chromosome 10q [12], contractions in which do not cause FSHD, also contributed to this skepticism. Several genes in the vicinity of D4Z4 were considered as potential candidates, but none could be definitively linked to FSHD through biochemical or genetic studies [30].

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    *

    Present address: University Medical Center Nijmegen, Department of Dermatology, 6500 HB Nijmegen, The Netherlands

    Present address: Children's Hospital Oakland, Oakland, California 94609, USA

    To whom correspondence and reprint requests should be addressed. Fax: +44-115-970-9906. E-mail: [email protected].

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