PMID- 18724050
OWN - NLM
STAT- MEDLINE
DCOM- 20081218
LR  - 20190805
IS  - 1660-9263 (Print)
IS  - 1660-9263 (Linking)
VI  - 1
DP  - 2006
TI  - The genomic basis of disease, mechanisms and assays for genomic disorders.
PG  - 1-16
LID - 10.1159/000092496 [doi]
AB  - In the past fifteen years, an emerging group of genetic diseases have been 
      described that result from DNA rearrangements rather than from single nucleotide 
      changes. Such conditions have been referred to as genomic disorders. The 
      predominant molecular mechanism underlying the rearrangements that cause this 
      group of diseases and traits is nonallelic homologous recombination (NAHR) 
      (unequal crossing-over between chromatids or chromosomes) utilizing low-copy 
      repeats (LCRs) (also known as segmental duplications) as substrates. In 
      contradistinction to highly repetitive sequences (e.g. Alu and LINE elements), 
      these higher-order genomic architectural features usually span >1kb and up to 
      hundreds of kilobases of genomic DNA, share >96% sequence identity and constitute 
      >5% of the human genome. Many LCRs have complex structure and have arisen during 
      primate speciation as a result of serial segmental duplications. LCRs can 
      stimulate and/or mediate constitutional (both recurrent and nonrecurrent), 
      evolutionary, and somatic rearrangements. Recently, copy-number variations 
      (CNVs), also referred to as large-scale copy-number variations (LCVs) or 
      copy-number polymorphisms (CNPs), parenthetically often associated with LCRs, 
      have been demonstrated as a source of human variation as well as a potential 
      cause of diseases. In addition to fluorescence in situ hybridization (FISH), 
      pulsed-field gel electrophoresis (PFGE), and in silico analyses, multiplex 
      ligation-dependent probe amplification (MLPA), and array comparative genomic 
      hybridization (aCGH) with BAC and PAC clones have proven to be useful diagnostic 
      methods for the detection and characterization of DNA rearrangements with the 
      latter enabling high-resolution genome-wide analysis. The clinical implementation 
      of such techniques is revolutionizing clinical cytogenetics.
FAU - Stankiewicz, P
AU  - Stankiewicz P
AD  - Department of Molecular & Human Genetics, Baylor College Medicine, Houston, Tex., 
      USA.
FAU - Lupski, J R
AU  - Lupski JR
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Switzerland
TA  - Genome Dyn
JT  - Genome dynamics
JID - 101319425
SB  - IM
MH  - *Comparative Genomic Hybridization
MH  - Genetic Diseases, Inborn/*diagnosis/*genetics
MH  - Genetic Techniques
MH  - Genetics
MH  - *Genome, Human
MH  - Humans
MH  - Models, Genetic
MH  - Recombination, Genetic
RF  - 102
EDAT- 2008/08/30 09:00
MHDA- 2008/12/19 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2008/12/19 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - 000092496 [pii]
AID - 10.1159/000092496 [doi]
PST - ppublish
SO  - Genome Dyn. 2006;1:1-16. doi: 10.1159/000092496.