Identification of human haploinsufficient genes and their genomic proximity to segmental duplications

Dang, Vinh T., Kassahn, Karin S., Marcos, Andres Esteban and Ragan, Mark A. (2008) Identification of human haploinsufficient genes and their genomic proximity to segmental duplications. European Journal of Human Genetics, 16 11: 1350-1357. doi:10.1038/ejhg.2008.111

Author Dang, Vinh T.
Kassahn, Karin S.
Marcos, Andres Esteban
Ragan, Mark A.
Title Identification of human haploinsufficient genes and their genomic proximity to segmental duplications
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
Publication date 2008-11
Year available 2008
Sub-type Article (original research)
DOI 10.1038/ejhg.2008.111
Volume 16
Issue 11
Start page 1350
End page 1357
Total pages 8
Editor Gert-Jan B. van Ommen
Place of publication London, England
Publisher Nature Publishing Group
Collection year 2009
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060408 Genomics
Formatted abstract
Despite the significance of haploinsufficiency in human disease, no systematic study has been reported into the types of genes that are haploinsufficient in human, or into the mechanisms that commonly lead to their deletion and to the expression of the haploinsufficient phenotype. We have applied a rigorous text-searching and database-mining strategy to extract, as comprehensively as possible, from PubMed and OMIM an annotated list of currently known human haploinsufficient genes, including their functions and associated diseases. Gene-set enrichment analysis shows that genes-encoding transcription factors, and genes that function in development, the cell cycle, and nucleic acid metabolism are overrepresented among haploinsufficient genes in human. Many of the phenotypes associated with loss-of-function or deletion of one copy of a haploinsufficient gene describe mental retardation, developmental or metabolic disorders, or tumourigenesis. We also found that haploinsufficient genes are less likely than the complete set of human genes to be situated between pairs of segmental duplications (SDs) that are in close proximity to each other on the same chromosome. Given that SDs can initiate non-allelic homologous recombination (NAHR) and the deletion of adjacent genomic regions, this suggests that the location of haploinsufficient genes between SD pairs, from whence they may suffer intra-genomic rearrangement and loss, is selectively disadvantageous. We describe a custom-made Java visualization tool, HaploGeneMapper, to aid in visualizing the proximity of human haploinsufficient genes to SDs and to enable identification of haploinsufficient genes that are vulnerable to NAHR-mediated deletion. European Journal of Human Genetics (2008) 16, 1350-1357; doi:10.1038/ejhg.2008.111; published online 4 June 2008
Keyword haploinsufficiency genes
segmental duplications
copy number variation
low-copy repeats
non-allelic homologous recombination
human genome
Q-Index Code C1
Q-Index Status Provisional Code
Additional Notes Published online 4 June 2008.

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Created: Fri, 12 Jun 2009, 11:48:58 EST by Jennifer Greder on behalf of Institute for Molecular Bioscience