Detailed Sequence Analysis of the Distal Down
Syndrome Critical Region and the SOD1/AML1 Region
on Chromosome 21
Todd Taylor 1
taylor@hgc.ims.u-tokyo.ac.jp
Tomomi Shobu 1
shobu@ims.u-tokyo.ac.jp

Masahira Hattori 1
hattori@ims.u-tokyo.ac.jp
Kazuo Ishii 1
ishii@jet.sci.kitasato-u.ac.jp
Yoshiyuki Sakaki 1

Kiyoteru Noguchi 2
k-noguchi@comp.hitachi.co.jp
Atsushi Toyoda 1

toyoda@jet.sci.kitasato-u.ac.jp

sakaki@ims.u-tokyo.ac.jp

12

Human Genome Center, Institute of Medical Science, University of Tokyo
4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Hitachi, Ltd., Hitachi Omori 2nd Bldg., 27-18, Minami Oi 6-chome, Shinagawa-ku,Tokyo 140-8572, Japan

1 Introduction
Down syndrome (MIM 190685) is the most common genetic form of mental retardation. It is causedby trisomy of all or a portion of chromosome 21. The 2.5-Mb region [3, 4] between DNA markers
D21S17 and ERG (MIM 165080) is associated with the main features of Down syndrome and is termed
the Down syndrome critical region.
As part of the human genome project, our laboratory is studying the physical structure of humanchromosome 21. To identify the genes and functional units mapped on chromosome 21, we are focusing
on the physical mapping and sequencing of several regions. One region we have sequenced is the distal
1.6-Mb end of the Down syndrome critical region. The 4-Mb region from the SOD1 gene (MIM147450) to the AML1 (MIM 151385) gene will soon be completely sequenced. This study describes
the detailed sequence analysis of these two regions of chromosome 21.

2 Methods
Completed sequences are analyzed using several programs available on the Internet. Many of theprograms use di erent input formats and require that analyses be run one at a time. Most of these
programs can be run by cutting the large sequences into small, overlapping fragments and then saving them in FASTA format. For many of the analyses, the Baylor College of Medicine Search Launcher
Batch Client is used to interface with their WWW server (http://gc.bcm.tmc.edu:8088/search-launcher/launcher.html) [5]. The batch client reads in multiple input les, performs several di erent searches(i.e., BLAST [1]), and stores the results on the user's computer as individual HTML les. The output
les are parsed using several Perl scripts [2], and then the data is cleaned up and transferred to adatabase. The results are displayed graphically and conclusions are drawn. If necessary, sub-regionsof the sequence are re-BLASTed under di erent parameters.

3 Results
A summary of the chromosome 21 analysis will be presented.
384

Figure 1: Sequence analysis owchart.

References[1] Altschul, S.F., Madden, T.L., Scha er, A.A., Zhang, J., Zhang, Z., Miller, W. and Lipman, D.J.,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic
Acids Res., 25: 3389{3402, 1997.
[2] Wall, L., Christiansen, T. and Schwartz, R.L., Programming Perl (Second Edition), O'Reilly &Associates, Inc., Sebastopol, 1996.
[3] Lucente, D., Chen, H.M., Shea, D., Samec, S.N., Rutter, M., Chrast, R., Rossier, C., Buckler, A.,
Antonarakis, S.E. and McCormick, M.K., Localization of 102 exons to a 2.5 Mb region involved
in Down syndrome, Hum. Mol. Genet., 4:1305{1311, 1995.
[4] Peterson, A., Patil, N., Robbins, C., Wang, L., Cox, D.R. and Myers, R.M., A transcript map ofthe Down syndrome critical region on chromosome 21, Hum Mol. Genet., 3:1735{1742, 1994.
[5] Smith, R.F., Wiese, B.A., Wojzynski, M.K., Davison, D.B. and Worley, K.C., BCM Search
Launcher{an integrated interface to molecular biology data base search and analysis services
available on the World Wide Web, Genome Res., 6:454{462, 1996.

385