title: Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity.
abstract: A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric-directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non-homologous interchromosomal exchange.
authors.affiliation: Human Genome Center, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. eichler1@llnl.gov
authors.forename: E E
authors.initials: EE
authors.lastname: Eichler
authors.forename: M L
authors.initials: ML
authors.lastname: Budarf
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: L L
authors.initials: LL
authors.lastname: Deaven
authors.forename: N A
authors.initials: NA
authors.lastname: Doggett
authors.forename: A
authors.initials: A
authors.lastname: Baldini
authors.forename: D L
authors.initials: DL
authors.lastname: Nelson
authors.forename: H W
authors.initials: HW
authors.lastname: Mohrenweiser
mesh_terms: D000326:Adrenoleukodystrophy / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D002503:Centromere / Q000235:genetics*; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D017421:Sequence Analysis / Q000379:methods; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome