Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease

被引:355
作者
Shaw, CJ
Lupski, JR
机构
[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[3] Texas Childrens Hosp, Houston, TX 77030 USA
关键词
D O I
10.1093/hmg/ddh073
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The term 'genomic disorder' refers to a disease that is caused by an alteration of the genome that results in complete loss, gain or disruption of the structural integrity of a dosage sensitive gene(s). In most of the common chromosome deletion/duplication syndromes, the rearranged genomic segments are flanked by large (usually > 10 kb), highly homologous low copy repeat (LCR) structures that can act as recombination substrates. Recombination between non-allelic LCR copies, also known as non-allelic homologous recombination, can result in deletion or duplication of the intervening segment. Recent findings suggest that other chromosomal rearrangements, including reciprocal, Robertsonian and jumping translocations, inversions, isochromosomes and small marker chromosomes, may also involve susceptibility to rearrangement related to genome structure or architecture. In several cases, LCRs, AT-rich palindromes and pericentromeric repeats are located at such rearrangement breakpoints. Analysis of the products of recombination at the junctions of the rearrangements reveals both homologous recombination and non-homologous end joining as causative mechanisms. Thus, a more global concept of genomic disorders emerges in which susceptibility to rearrangements occurs due to underlying complex genomic architecture. Interestingly, this architecture plays a role not only in disease etiology, but also in primate genome evolution. In this review, we discuss recent advances regarding general mechanisms for the various rearrangements of our genome, and potential models for rearrangements with non-homologous breakpoint regions.
引用
收藏
页码:R57 / R64
页数:8
相关论文
共 85 条
  • [1] Palindrome resolution and recombination in the mammalian germ line
    Akgun, E
    Zahn, J
    Baumes, S
    Brown, G
    Liang, F
    Romanienko, PJ
    Lewis, S
    Jasin, M
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (09) : 5559 - 5570
  • [2] ASHLEY T, 1994, HUM GENET, V94, P587, DOI 10.1007/BF00206950
  • [3] Fluorescence in situ hybridization with a synthetic (T(2)AG(3))(n) polynucleotide detects several intrachromosomal telomere-like repeats on human chromosomes
    Azzalin, CM
    Mucciolo, E
    Bertoni, L
    Giulotto, E
    [J]. CYTOGENETICS AND CELL GENETICS, 1997, 78 (02): : 112 - 115
  • [4] Shuffling of genes within low-copy repeats on 22qll (LCR22) by Alu-mediated recombination events during evolution
    Babcock, M
    Pavlicek, A
    Spiteri, E
    Kashork, CD
    Ioshikhes, I
    Shaffer, LG
    Jurka, J
    Morrow, BE
    [J]. GENOME RESEARCH, 2003, 13 (12) : 2519 - 2532
  • [5] An Alu transposition model for the origin and expansion of human segmental duplications
    Bailey, JA
    Liu, G
    Eichler, EE
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (04) : 823 - 834
  • [6] Human-specific duplication and mosaic transcripts: The recent paralogous structure of chromosome 22
    Bailey, JA
    Yavor, AM
    Viggiano, L
    Misceo, D
    Horvath, JE
    Archidiacono, N
    Schwartz, S
    Rocchi, M
    Eichler, EE
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (01) : 83 - 100
  • [7] Segmental duplications: Organization and impact within the current Human Genome Project assembly
    Bailey, JA
    Yavor, AM
    Massa, HF
    Trask, BJ
    Eichler, EE
    [J]. GENOME RESEARCH, 2001, 11 (06) : 1005 - 1017
  • [8] Monosomy 1p36 breakpoint junctions suggest pre-meiotic breakage-fusion-bridge cycles are involved in generating terminal deletions
    Ballif, BC
    Yu, W
    Shaw, CA
    Kashork, CD
    Shaffer, LG
    [J]. HUMAN MOLECULAR GENETICS, 2003, 12 (17) : 2153 - 2165
  • [9] The breakpoint region of the most common isochromosome, i(17q), in human neoplasia is characterized by a complex genomic architecture with large, palindromic, low-copy repeats
    Barbouti, A
    Stankiewicz, P
    Nusbaum, C
    Cuomo, C
    Cook, A
    Höglund, M
    Johansson, B
    Hagemeijer, A
    Park, SS
    Mitelman, F
    Lupski, JR
    Fioretos, T
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (01) : 1 - 10
  • [10] Mutational mechanisms of Williams-Beuren syndrome deletions
    Bayés, M
    Magano, LF
    Rivera, N
    Flores, R
    Jurado, LAP
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (01) : 131 - 151