genomic disorders molecular mechanisms for rearrangements and conveyed phenotypes重组基因疾病分子机制和转达了表型.pdfVIP

Review Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes James R. Lupski*, Pawel Stankiewicz ABSTRACT homologous recombination (HR) appears to be the predominant pathway underlying recurrent rearrangements earrangements of our genome can be responsible for of our genome. Regardless of mechanism, structural features R inherited as well as sporadic traits. The analyses of of the genome can predispose a particular region to chromosome breakpoints in the proximal short arm rearrangement. Determining the architectural features that of Chromosome 17 (17p) reveal nonallelic homologous result in the instability of the genomic regions has profound recombination (NAHR) as a major mechanism for recurrent consequences for clinical genetics as new technologies enable rearrangements whereas nonhomologous end-joining (NHEJ) high-resolution analysis of the human genome. This review can be responsible for many of the nonrecurrent will focus on the information culled from, and molecular rearrangements. Genome architectural features consisting of mechanisms elucidated by, breakpoint analyses of disease- low-copy repeats (LCRs), or segmental duplications, can associated rearrangements involving proximal 17p. Although stimulate and mediate NAHR, and there are hotspots for the the focus is 17p, such mechanisms appear to be generally crossovers within the LCRs. Rearrangements introduce applicable to all regions of the human genome. We also variation into our genome for selection to act upon and as describe the many mechanisms by wh