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Analysis of segmental duplications reveals a distinct pattern of continuation-of-synteny between human and mouse genomes

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Abstract

About 5% of the human genome consists of large-scale duplicated segments of almost identical sequences. Segmental duplications (SDs) have been proposed to be involved in non-allelic homologous recombination leading to recurrent genomic variation and disease. It has also been suggested that these SDs are associated with syntenic rearrangements that have shaped the human genome. We have analyzed 14 members of a single family of closely related SDs in the human genome, some of which are associated with common inversion polymorphisms at chromosomes 8p23 and 4p16. Comparative analysis with the mouse genome revealed syntenic inversions for these two human polymorphic loci. In addition, 12 of the 14 SDs, while absent in the mouse genome, occur at the breaks of synteny; suggesting a non-random involvement of these sequences in genome evolution. Furthermore, we observed a syntenic familial relationship between 8 and 12 breakpoint-loci, where broken synteny that ends at one family member resumes at another, even across different chromosomes. Subsequent genome-wide assessment revealed that this relationship, which we named continuation-of-synteny, is not limited to the 8p23 family and occurs 46 times in the human genome with high frequency at specific chromosomes. Our analysis supports a non-random breakage model of genomic evolution with an active involvement of segmental duplications for specific regions of the human genome.

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Acknowledgments

The study was supported by grants from NIGMS (GM068875) and NARSAD Young Investigator Award (to RAO).

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Authors and Affiliations

  1. Center for Neurobehavioral Genetics, Neuropsychiatric Institute, University of California Los Angeles, Gonda Building Room 3506, 695 Charles E. Young Drive South, Los Angeles, CA, 90095, USA

    Michael R. Mehan, Maricel Almonte, Erin Slaten, Nelson B. Freimer & Roel A. Ophoff

  2. Department of Human Genetics, University of California Los Angeles, Gonda Building Room 3506, 695 Charles E. Young Drive South, Los Angeles, CA, 90095, USA

    Roel A. Ophoff

  3. Molecular Cytogenetics Laboratories, Department of Pathology, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA

    P. Nagesh Rao

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  1. Michael R. Mehan
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  2. Maricel Almonte
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  3. Erin Slaten
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  4. Nelson B. Freimer
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  5. P. Nagesh Rao
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  6. Roel A. Ophoff
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Correspondence to Roel A. Ophoff.

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Mehan, M.R., Almonte, M., Slaten, E. et al. Analysis of segmental duplications reveals a distinct pattern of continuation-of-synteny between human and mouse genomes. Hum Genet 121, 93–100 (2007). https://doi.org/10.1007/s00439-006-0277-z

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  • DOI: https://doi.org/10.1007/s00439-006-0277-z

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