Recent Segmental Duplications in the Human Genome
Jeffrey A. Bailey,1
Zhiping Gu,2
Royden A. Clark,1
Knut Reinert,2
Rhea V. Samonte,1
Stuart Schwartz,1
Mark D. Adams,2
Eugene W. Myers,2
Peter W. Li,2
Evan E. Eichler1*
Primate-specific segmental duplications are considered
important in human disease and evolution. The inability to distinguish between allelic and duplication sequence overlap has hampered their
characterization as well as assembly and annotation of our genome. We
developed a method whereby each public sequence is analyzed at the
clone level for overrepresentation within a whole-genome shotgun
sequence. This test has the ability to detect duplications larger than
15 kilobases irrespective of copy number, location, or high sequence
similarity. We mapped 169 large regions flanked by highly similar
duplications. Twenty-four of these hot spots of genomic instability
have been associated with genetic disease. Our analysis indicates a
highly nonrandom chromosomal and genic distribution of recent segmental
duplications, with a likely role in expanding protein diversity.
1 Department of Genetics, Center for
Computational Genomics, and Center for Human Genetics, Case Western
Reserve University School of Medicine and University Hospitals of
Cleveland, Cleveland, OH 44106, USA.
2 Celera
Genomics, 45 West Gude Drive, Rockville, MD 20850, USA.
*
To whom correspondence should be addressed. E-mail:
eee{at}cwru.edu
