1. Finishing the human genome sequence?
2001 draft
90% of euchromatic sequence
Gaps: 150,000
Estimate of total number of protein-coding genes: ~30,000
2004 draft
99% of euchromatic sequence
Gaps: 341
Error rate: 1/100,000
Estimate of total number of protein-coding genes: 20,000-25,000
In 2001, the International Human Genome Sequencing Consortium (IHGSC) and the Celera Genomics corporation announced the completion of the first draft of the human genome sequence; however, these sequences were far from complete. For example, the initial IHGSC sequence covered only 90% of the gene-rich euchromatic region of the genome and had an estimated 150,000 gaps. A draft published in October of 2004 provided a substantial improvement over the sequence that had been released in Using a broad array of existing techniques (including the whole genome shotgun method), the IHGSC was able to produce a draft that covered 99% of the euchromatic portion of the human genome with an error rate of 1/100,000 and only 341 gaps. The more refined genome sequence along with improved gene prediction algorithms further allowed the IHGSC to revise the number of protein-coding genes from the original 30,000 to a range of 20,000 to 25,000.
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458

2. Comparing the 2001 and 2004 drafts
The graph in the slide shows a base pair by base pair comparison of the chromosome 7 sequence from the 2001 and 2004 drafts. If the two sequences had been identical, the line would be straight, continuous, and at a 45 degree angle. Breaks in the line represent gaps in the first draft and smaller perpendicular segments represent areas that had been improperly inverted in the initial draft. The larger graph is done at megabase (Mb) resolution, and the inset shows a smaller region at kilobase (kb) resolution. While the 2004 draft is a significant improvement over the 2001 sequence, it still omits the 20% of the human genome found in heterochromatin, a highly repetitive region that is implicated in replication and other chromosomal processes. Unfortunately, current technologies are not sufficient to deal with such highly repetitive sequences, suggesting that the human genome may not be fully sequenced for several years to come.
From Figure 1 in International Human Genome Sequencing Consortium (2004) “Finishing the euchromatic sequence of the human genome” Nature 431:
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458