Hybridization analysis of D4Z4 repeat arrays linked to FSHD

被引:19
作者
Ehrlich, Melanie [1 ]
Jackson, Kesmic
Tsumagari, Koji
Camano, Pilar
Lemmers, Richard J. F. L.
机构
[1] Tulane Med Sch, Program Human Genet, New Orleans, LA USA
[2] Tulane Med Sch, Dept Biochem, New Orleans, LA USA
[3] Hosp Donostia, Unidad Expt, San Sebastian, Spain
[4] Leiden Univ, Ctr Med, Leiden, Netherlands
关键词
D O I
10.1007/s00412-006-0080-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease involving shortening of D4Z4, an array of tandem 3.3-kb repeat units on chromosome 4. These arrays are in subtelomeric regions of 4q and 10q and have 1-100 units. FSHD is associated with an array of 1-10 units at 4q35. Unambiguous clinical diagnosis of FSHD depends on determining the array length at 4q35, usually with the array-adjacent p13E-11 probe after pulsed-field or linear gel electrophoresis. Complicating factors for molecular diagnosis of FSHD are the phenotypically neutral 10q D4Z4 arrays, cross-hybridizing sequences elsewhere in the genome, deletions including the genomic p13E-11 sequence and part of D4Z4, translocations between 4q and 10q D4Z4 arrays, and the extremely high G+C content of D4Z4 arrays (73%). In this study, we optimized conditions for molecular diagnosis of FSHD with a 1-kb D4Z4 subfragment probe after hybridization with p13E-11. We demonstrate that these hybridization conditions allow the identification of FSHD alleles with deletions of the genomic p13E-11 sequence and aid in determination of the nonpathogenic D4Z4 arrays at 10q. Furthermore, we show that the D4Z4-like sequences present elsewhere in the genome are not tandemly arranged, like those at 4q35 and 10q26.
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页码:107 / 116
页数:10
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