This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: 1929904v1 14/2/239    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leem, S.-H. Articles by Larionov, V. Search for Related Content PubMed PubMed Citation Articles by Leem, S.-H. Articles by Larionov, V. Social Bookmarking                   What's this?

Letter

Closing the Gaps on Human Chromosome 19 Revealed Genes With a High Density of Repetitive Tandemly Arrayed Elements

¹ Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute (NCI, NIH), Bethesda, Maryland, 20892, USA ² Department of Biology, Dong-A University, Busan 604-714, Korea ³ Department of Genetics, Stanford University School of Medicine, Stanford, California, 94305, USA ⁴ U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, 94598, USA

The reported human genome sequence includes about 400 gaps of unknown sequence that were not found in the bacterial artificial chromosome (BAC) and cosmid libraries used for sequencing of the genome. These missing sequences correspond to 1% of euchromatic regions of the human genome. Gap filling is a laborious process because it relies on analysis of random clones of numerous genomic BAC or cosmid libraries. In this work we demonstrate that closing the gaps can be accelerated by a selective recombinational capture of missing chromosomal segments in yeast. The use of both methodologies allowed us to close the four remaining gaps on the human chromosome 19. Analysis of the gap sequences revealed that they contain several abnormalities that could result in instability of the sequences in microbe hosts, including large blocks of micro- and minisatellites and a high density of Alu repeats. Sequencing of the gap regions, in both BAC and YAC forms, allowed us to generate a complete sequence of four genes, including the neuronal cell signaling gene SCK1/SLI. The SCK1/SLI gene contains a record number of minisatellites, most of which are polymorphic and transmitted through meiosis following a Mendelian inheritance. In conclusion, the use of the alternative recombinational cloning system in yeast may greatly accelerate work on closing the remaining gaps in the human genome (as well as in other complex genomes) to achieve the goal of annotation of all human genes.

⁵ Corresponding author.
E-MAIL larionov{at}mail.nih.gov; FAX (301) 480-2772.

[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to DDBJ under accession nos. AC140008, AY207046, and AY345879.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. P. Kumar, S. Mehta, P. K. Purbey, D. Notani, R. S. Jayani, H. J. Purohit, D. V. Raje, D. S. Ravi, R. R. Bhonde, D. Mitra, et al. SATB1-Binding Sequences and Alu-Like Motifs Define a Unique Chromatin Context in the Vicinity of Human Immunodeficiency Virus Type 1 Integration Sites J. Virol., June 1, 2007; 81(11): 5617 - 5627. [Abstract] [Full Text] [PDF]

				I. Horikawa, Y. J. Chiang, T. Patterson, L. Feigenbaum, S.-H. Leem, E. Michishita, V. Larionov, R. J. Hodes, and J. C. Barrett Differential cis-regulation of human versus mouse TERT gene expression in vivo: Identification of a human-specific repressive element PNAS, December 20, 2005; 102(51): 18437 - 18442. [Abstract] [Full Text] [PDF]