Large-Scale Copy Number Polymorphism in the Human Genome

@article{Sebat2004LargeScaleCN,
  title={Large-Scale Copy Number Polymorphism in the Human Genome},
  author={Jonathan Sebat and B. Lakshmi and Jennifer Troge and Joan Alexander and Janet M. Young and P{\"a}r Lundin and Susanne M{\aa}n{\'e}r and Hillary F. Massa and Megan Walker and Maoyen Chi and Nicholas E. Navin and Robert Lucito and John Healy and James Hicks and Kenny Q. Ye and Andrew Reiner and T. Conrad Gilliam and Barbara J. Trask and Nick J. Patterson and Anders Zetterberg and Michael Wigler},
  journal={Science},
  year={2004},
  volume={305},
  pages={525 - 528}
}
The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length… 
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References

SHOWING 1-10 OF 84 REFERENCES
Recent Segmental Duplications in the Human Genome
TLDR
A method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity.
Large-scale variation among human and great ape genomes determined by array comparative genomic hybridization.
TLDR
Results of an evolutionary analysis utilizing array comparative genomic hybridization (array CGH) indicate extensive local repatterning of hominoid chromosomes in euchromatic regions through a duplication-driven mechanism of genome evolution.
Analysis of primate genomic variation reveals a repeat-driven expansion of the human genome.
TLDR
Orthologous comparisons with the chimpanzee suggest that the human genome continues to significantly expand due to shifts in retrotransposition activity, and it is estimated that human euchromatin has expanded 30 Mb and 550 Mb compared to the primate genomes of chimpanzee and lemur, respectively.
Polymorphically duplicated genes: their relevance to phenotypic variation in humans
TLDR
There is evidence that polymorphic gene duplication may be common and a growing number of genes are known to be duplicated in a polymorphic manner although phenotypes cannot be associated with most of these.
Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation.
TLDR
ROMA (representational oligonucleotide microarray analysis) will assist in the discovery of genes and markers important in cancer, and theiscovery of loci that may be important in inherited predisposition to disease.
Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease.
TLDR
A more global concept of genomic disorders emerges in which susceptibility to rearrangements occurs due to underlying complex genomic architecture, and this architecture plays a role not only in disease etiology, but also in primate genome evolution.
A tiling resolution DNA microarray with complete coverage of the human genome
TLDR
The constructed tiling resolution array allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease and shows the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers.
BAC microarray analysis of 15q11–q13 rearrangements and the impact of segmental duplications
TLDR
Results indicate that the duplication composition of BAC substrates may affect the sensitivity for detecting dosage variation, and have important implications for effective microarray design, as well as for the detection of segmental aneusomy within the human population.
Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates.
TLDR
Comparative DNA sequence studies between humans and nonhuman primates are compared to identify genomic rearrangements that have occurred frequently during primate genome evolution and significantly contribute to the DNA differences between these species.
Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster.
TLDR
It is shown that a cluster of at least three antimicrobial beta-defensin genes (DEFB4, DEFB103, and DEFB104) at 8p23.1 are polymorphic in copy number, with a repeat unit >/=240 kb long, which is likely to have important consequences for immune system function.
...
1
2
3
4
5
...