RT Journal
A1 Leem, Sun-Hee
A1 Kouprina, Natalay
A1 Grimwood, Jane
A1 Kim, Jung-Hyun
A1 Mullokandov, Michael
A1 Yoon, Young-Ho
A1 Chae, Ji-Youn
A1 Morgan, Jenna
A1 Lucas, Susan
A1 Richardson, Paul
A1 Detter, Chris
A1 Glavina, Tijana
A1 Rubin, Eddy
A1 Barrett, J. Carl
A1 Larionov, Vladimir
T1 Closing the Gaps on Human Chromosome 19 Revealed Genes With a High Density of Repetitive Tandemly Arrayed Elements
JF Genome Research 
JO Genome Research 
YR 2004 
FD February 01 
VO 14 
IS 2 
SP 239 
OP 246 
DO 10.1101/gr.1929904 
UL http://genome.cshlp.org/content/14/2/239.abstract 
AB 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.