title: Sequence homology between 4qter and 10qter loci facilitates the instability of subtelomeric KpnI repeat units implicated in facioscapulohumeral muscular dystrophy.
abstract: Physical mapping and in situ hybridization experiments have shown that a duplicated locus with a structural organization similar to that of the 4q35 locus implicated in facioscapulohumeral muscular dystrophy is present in the subtelomeric portion of 10q. We performed sequence analysis of the p13E-11 probe and of the adjacent KpnI tandem-repeat unit derived from a 10qter cosmid clone and compared our results with those published, by other laboratories, for the 4q35 region. We found that the sequence homology range is 98%-100% and confirmed that the only difference that can be exploited for differentiation of the 10qter from the 4q35 alleles is the presence of an additional BlnI site within the 10qter KpnI repeat unit. In addition, we observed that the high degree of sequence homology does facilitate interchromosomal exchanges resulting in displacement of the whole set of BlnI-resistant or BlnI-sensitive KpnI repeats from one chromosome to the other. However, partial translocations escape detection if the latter simply relies on the hybridization pattern from double digestion with EcoRI/BlnI and with p13E-11 as a probe. We discovered that the restriction enzyme Tru9I cuts at both ends of the array of KpnI repeats of different chromosomal origins and allows the use of cloned KpnI sequences as a probe by eliminating other spurious fragments. This approach coupled with BlnI digestion permitted us to investigate the structural organization of BlnI-resistant and BlnI-sensitive units within translocated chromosomes of 4q35 and 10q26 origin. A priori, the possibility that partial translocations could play a role in the molecular mechanism of the disease cannot be excluded.
authors.affiliation: Istituto di Biologia Cellulare, Consiglio Nazionale Ricerche, Università "Tor Vergata," Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cacurri
authors.forename: N
authors.initials: N
authors.lastname: Piazzo
authors.forename: G
authors.initials: G
authors.lastname: Deidda
authors.forename: E
authors.initials: E
authors.lastname: Vigneti
authors.forename: G
authors.initials: G
authors.lastname: Galluzzi
authors.forename: L
authors.initials: L
authors.lastname: Colantoni
authors.forename: B
authors.initials: B
authors.lastname: Merico
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: L
authors.initials: L
authors.lastname: Felicetti
mesh_terms: D001483:Base Sequence; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003001:Cloning, Molecular; D015342:DNA Probes / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; C055927:endodeoxyribonuclease MseI; C064053:CCTAGG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C029312:GGTACC-specific type II deoxyribonucleases