Background

As Tables 1 & 2 shows Genome Centers around the world are making rapid progress sequencing genomes of various organisms.
 

 
Sources: Genome Sequencing Projects (MAGPIE); Genomes in Public Databases, Genomes Statistics, GMT,
TIGR Microbial Database & TIGR Genomes in progress, DOE Microbial Genomes Project: Organisms in the Program: Complete and in Progress,  GenoscopeProjects

Progress on the Human Genome is increasing and at the current time the fraction of the Human Genome that has been sequenced is 24.7% (+66.2% in draft form, as of Sept. 18, 2000).  This data is available in public databases.  An additional 85,000+ gene sequence clusters from cDNA's representing ~100 Mbases (3% of human genome) is present in public and private database (Unigene and comments made by Incyte and HGS at public conferences).  In 1996, only ~20 MBases/year of large scale sequencing capacity was directed towards the HGP.  This has lead the Wellcome Trust to commit to providing the funding to increase the capacity of the Sanger Center to allow it to sequence 1/6th of the Human Genome (500 MBases) which would require a minimum capacity of 150 MBases / year (assuming a coverage of 2).  The entry of Celera Genomics in late 1998 caused the NIH to significantly accelerate genome sequencing in 1999, so estimates for the completion of the genome are now in the 2001-2002 time period.  In September of 1999, Incyte announced that it predicted the number of human genes would be between 129,769 and 142,634.
 

The requirements for sequencing capacity for the HGP underestimate the overall requirements for sequencing capacity.  There are projects, initial efforts, plans or good scientific reasons for doing the genomes of  the 50 major human disease causing organisms (500+ Mbp), Drosophila (~120 Mbp of coding sequence), Mouse (3 Gbp) and Zebrafish (1.7 Gbp).

In agriculture, mapping or sequencing projects are in progress for Cattle (3 Gbp), Pig (2.7 Gbp), Sheep, Chicken (1.2 Gbp), Arabidopsis (100 Mbp), Maize (5 Gbp), Rice (400 Mbp), Barley, Bean, Cotton, Lettuce, Mushroom, Pine, Rye, Sorghum, Sugarcane, Wheat, Apple, Brassicas, Cabbage, Clover, Cucumber, Grass, Lilium, Pea, Peach, Rye, Snapdragon, Spruce, Tobacco, Tomato,  Alfalfa, Almond, Asparagus, Berry, Carrot, Celery, Chrysanthemum, Citrus, Clover, Cocoa, Cotton, Cucumber, Cuphea, Lentil, Oat, Onion, Papaya, Pea, Peach, Peanut, Pear, Pepper, Pine, Plum, Poplar, Potato, Rice, Rose, Soybean, Spruce, Squash, Sugarcane, Sunflower and Turf Grass.

The sequencing requirements for these organisms should exceed 200 billion base pairs!

The Stanford Genome Center, SW Medical Center, and the Whitehead Institute have devoted significant resources to the developing highly automated high throughput methods for genome mapping and sequencing. The Stanford Genome Center intends to make available in October of 1997, the parts lists, plans and diagrams for the automated machines which have been developed for genome sequencing (www-sghc.stanford.edu).  Estimates from Stanford, place the current cost for finished DNA sequence information at around $.25 per base by the year 2000, implying that Genome Centers which are sequencing 10 MB/year have budgets in excess of $2.5 million per year.

NIH grants in 1997 were targeting a cost of $.05 per base for genome sequencing.  These may not have taken into account the throughput increases that would be allowed by newer capillary sequencing machines.

In understanding sequencing, it is necessary to recognize that the bacterial and yeast genome sequencing which has been done thus far has emphasized shotgun sequencing methods.  This approach requires that the genome be randomly fragmented, sequenced to high redundancy and assembled by computer sequence matching of overlapping fragments.  Genomes sequenced in this way require raw sequence data from 5 to 10 times greater than the actual genome size.  The lowest redundancy levels reached thus far have been around 2.5x genome size by the University of Heidelberg on M. pneumoniae primarily using primer walking sequencing methods.  Current estimates from Stanford would place human genome sequencing requirements at 3-4x the genome size.

Table 3 lists the existing large scale genome centers and their current or planned participation in large scale sequencing efforts and the Human Genome Project.
 
 

There are several companies which have large amounts of sequencing capacity but which are not actively involved in the Human Genome Project as shown in Table 5.
 
 

At the current time these companies are focused primarily on human diseases with some emphasis on agricultural genomes.  It is not expected, with the exception of Genome Therapeutics that they will play a major role in genome sequencing at this time.

• NCBI's Human Genome Progress; Microbial Genomes
• How much of the human genome has been sequenced? by Jared Roach.
• TIGR Microbial Database
• Media Guide to The Human Genome Project
• euGenes Databases
• GenomeWeb: Prokaryotic Genome Databases
• ArcheaWeb Genomes
• EMBL: Genome Monitoring Table
• International Human Genome Sequencing Consortium, "Initial Sequencing and Analysis of the Human Genome", Nature 409:860-921 (15 Feb 2001).
• Pearson, H., "Human Gene Number Climbs", Nature News Service (24 August 2001).
• DOE Microbial Genomes Project: Organisms in the Program: Complete and in Progress (2002)
• Integrated Genomics: Gold (Genomes OnLine Database homepage);  Ergo
• Bernal, A., Ear, U., Kyrpides, N., "Genomes OnLine Database (GOLD): a monitor of genome projects world-wide", NAR 29:126-127 (2001).
• Kyrpides, N., "Genomes OnLine Database (GOLD): a monitor of complete and ongoing genome projects world wide", Bioinformatics 15:773-774  (1999).
• Rat Genome Project @ Baylor College of Medicine
• The Center for the Advancement of Genomics -- Genome News Network -- "A quick guide to sequenced genomes".
• Spencer, G., "Background on Comparative Genomic Analysis", NHGRI (Jan 2004).

1. Genome Sizes are typically measured in millions of base pairs (Mbp) or billions of base pares (Gbp), that is the number of A, C, G and T nucleotides.
2. This is the number of transcripts identified.  Transcripts may not produce functional genes.

• LLNL Instumentation (http://www-bio.llnl.gov/genome/html/05instrument.html )
• LBL Instrumentation (http://hgighub.lbl.gov/esd/HGCmain.htm )
• Sanger Center Instrumentation (http://www.sanger.ac.uk/Teams/Team52/)
• SW Medical Center Instrumentation (http://mcdermott.swmed.edu/gestec/automation/)
• Stanford HGC Instrumentation (http://sequence-www.stanford.edu/group/techdev/index.html)
• University of Oklahoma (http://dna1.chem.uoknor.edu/)

• Applied Biosytems (PE) (http://www2.perkin-elmer.com/ab/index.htm)
• Avantec, Inc. (manufacturer of MerMade oligonucleotide synthesizer)
• Curagen (http://www.curagen.com/); Sequencing apparatus for MIT/Whitehead genome center
• Beckman (http://www.beckman.com/biorsrch/prodinfo/biomek/bioinfo.htm)
• GeneSys Technologies (http://www.genesys-tech.com/); Univ. Wisconson offshoot for DNA sequencing
• Genomic Instrumentation Services (http://www.geneinst.com/); Stanford offshoot
• LiCor (http://www.licor.com/); Gel DNA sequencing apparatus
• Molecular Dynamics (http://www.mydyn.com/); Capillary DNA sequencing apparatus
• PBA Technologies (http://www.pbatech.co.uk/); Robots for the Sanger Center

• Profit vs. Science - Slashdot discussion regarding Science publication agreement with Celera.
• Database Of Genome Sizes (DOGS)
• CBS: Genome Atlas Database
• TIGR: Genomes Online Database (GOLD)
• TIGR: Comprehensive Microbial Resource (CMR)
• T.R.G.'s: Genome Size Database (GSD)
• Bioresearch UK: Protozoan Genomes Status
• GenomeCanada
• GNN: Genome News Network:
• A Quick Guide to Sequenced Organisms
• A complete list of sequenced organisms