Premium
Molecular Mechanisms for CMT1A Duplication and HNPP Deletion
Author(s) -
BOERKOEL C. F.,
INOUE K.,
REITER L. T.,
WARNER L. E.,
LUPSKI J. R.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08563.x
Subject(s) - non allelic homologous recombination , homologous recombination , biology , genetics , recombination , gene duplication , genome , gene rearrangement , human genome , homologous chromosome , genomic dna , segmental duplication , direct repeat , dna , genome instability , non homologous end joining , genetic recombination , gene , dna damage , gene family
As the best characterized human genomic disorders, 118 CMT1A and HNPP illustrate several common mechanistic features of genomic rearrangements. These features include the following: (1) Recombination occurs between homologous sequences flanking the duplicated/deleted genomic segment. (2) The evolution of the mammalian genome may result in an architecture consisting of region‐specific low‐copy repeats that predispose to rearrangement secondary to providing homologous regions as substrate for recombination. (3) Strand exchange occurs preferentially in a region of perfect sequence identity within the flanking repeat sequences. (4) Double‐strand breaks likely initiate recombination between the flanking repeats. (5) The mechanism and rate of homologous recombination resulting in DNA rearrangement may differ for male and female gametogenesis. (6) Homologous recombination resulting in DNA rearrangement occurs with high frequency in the human genome. (7) Genomic disorders result from structural features of the human genome and not population specific alleles or founder effects; therefore, genomic disorders appear to occur with equal frequencies in different world populations.