Analysis of the Organisation and Localisation of the FSHD-associated Tandem Array in Primates: Implications for the Origin and Evolution of the 3.3 Kb Repeat Family

Overview

Journal Chromosoma

Specialty Molecular Biology

Date 1996 Sep 1

PMID 8781186

Citations 14

Authors

L N Clark

U Koehler

D C Ward

J Wienberg

J E Hewitt

Affiliations

Soon will be listed here.

Abstract

The D4Z4 locus is a polymorphic tandem repeat sequence on human chromosome 4q35. This locus is implicated in the neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD). The majority of sporadic cases of FSHD are associated with de novo DNA deletions within D4Z4. However, it is still not known how this rearrangement causes FSHD. Although the repeat contains homeobox sequences, despite exhaustive searching, no transcript from this locus has been identified. Therefore, it has been proposed that the deletion may invoke a position effect on a nearby gene. In order to try to understand the role of the D4Z4 repeat in this disease, we decided to investigate its conservation in other species. In this study, the long-range organisation and localisation of loci homologous to D4Z4 were investigated in primates using Southern blot analysis, pulsed field gel electrophoresis and fluorescence in situ hybridisation. In humans, probes to D4Z4 identify, in addition to the 4q35 locus, a closely related tandem repeat at 10qter and many related repeat loci mapping to the acrocentric chromosomes; a similar pattern was seen in all the great apes. In Old World monkeys, however, only one locus was detected in addition to that on the homologue of human chromosome 4, suggesting that the D4Z4 locus may have originated directly from the progenitor locus. The finding that tandem arrays closely related to D4Z4 have been maintained at loci homologous to human chromosome 4q35-qter in apes and Old World monkeys suggests a functionally important role for these sequences.

Citing Articles

Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7.

Banerji C, Zammit P EMBO Mol Med. 2021; 13(8):e13695.

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Dark Matter of Primate Genomes: Satellite DNA Repeats and Their Evolutionary Dynamics.

Ahmad S, Singchat W, Jehangir M, Suntronpong A, Panthum T, Malaivijitnond S Cells. 2020; 9(12).

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Therapeutic Strategies Targeting DUX4 in FSHD.

Le Gall L, Sidlauskaite E, Mariot V, Dumonceaux J J Clin Med. 2020; 9(9).

PMID: 32906621 PMC: 7564105. DOI: 10.3390/jcm9092886.

Current status and future prospect of FSHD region gene 1.

Hansda A, Tiwari A, Dixit M J Biosci. 2017; 42(2):345-353.

PMID: 28569257 DOI: 10.1007/s12038-017-9681-x.

Polycomb repressive complex 1 provides a molecular explanation for repeat copy number dependency in FSHD muscular dystrophy.

Casa V, Runfola V, Micheloni S, Aziz A, Dilworth F, Gabellini D Hum Mol Genet. 2017; 26(4):753-767.

PMID: 28040729 PMC: 5409123. DOI: 10.1093/hmg/ddw426.

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