Abstract:
:Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicroscopic level, thereby directly linking disease phenotypes to gene dosage alterations. At present, the entire human genome can be scanned for deletions and duplications at over 30,000 loci simultaneously by array CGH ( approximately 100 kb resolution), thus entailing an attractive gene discovery approach for monogenic conditions, in particular those that are associated with reproductive lethality. Here, we review the present and future potential of microarray-based mapping of genes underlying monogenic diseases and discuss our own experience with the identification of the gene for CHARGE syndrome. We expect that, ultimately, genomic copy number scanning of all 250,000 exons in the human genome will enable immediate disease gene discovery in cases exhibiting single exon duplications and/or deletions.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Vissers LE,Veltman JA,van Kessel AG,Brunner HGdoi
10.1093/hmg/ddi268subject
Has Abstractpub_date
2005-10-15 00:00:00pages
R215-23eissn
0964-6906issn
1460-2083pii
14/suppl_2/R215journal_volume
14 Spec No. 2pub_type
杂志文章,评审abstract::LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a ...
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