Eichler E E, Budarf M L, Rocchi M, Deaven L L, Doggett N A, Baldini A, Nelson D L, Mohrenweiser H W
Human Genome Center, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Hum Mol Genet. 1997 Jul;6(7):991-1002. doi: 10.1093/hmg/6.7.991.
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.
一个包含X染色体肾上腺脑白质营养不良（ALD）基因座外显子7至10的9.7 kb片段已复制到人类染色体2p11、10p11、16p11和22q11着丝粒周围区域附近的特定位置。比较序列分析显示核苷酸同一性为92%至96%，这表明常染色体ALD旁系同源物是在高等灵长类动物进化过程中相对较近的时期（500万至1000万年前）出现的。对复制区域侧翼序列的分析确定存在一个不寻常的GCTTTTTGC重复序列，它可能是着丝粒定向转座过程中的一个序列特异性整合位点。断点序列和系统发育分析预测了一个两步转座模型，其中从Xq28到着丝粒2p11的一次复制发生后，一个更大的重复子盒在着丝粒区域之间迅速分布。除了有助于在ALD患者中更有效地检测突变外，这些发现还为着丝粒定向的非同源染色体间交换机制的分子基础提供了进一步的见解。
