Below is a description of three papers by Harvard medical faculty based at the school and at Massachusetts General Hospital and Brigham and Women's Hospital:

PAPER: "Comparison of Public and Private Draft Sequences of the Human Genome"

George Church and his colleagues have compared the draft sequences of the human genome, one produced by the publicly funded Human Genome Project and the other by Celera Genomics, which are the main topic of the special human genome issue of Nature and the corresponding issue of Science.

The researchers found that overall, the two sequences are very similar. Both are about the same size; both show about the same number of unique 15-base stretches; and both show very similar numbers of candidate binding sites for the two DNA binding proteins the team considered.

The researchers did see differences in the distribution of sequence gaps that corresponded to the different strategies the two teams used for sequence assembly.

At a detailed level, they also found one instance where the sequences were assembled in different ways. (Church and colleagues could not determine which, if either, of the two different assemblies was correct; they believe that the sequencing teams themselves will be tracking and working through differences at this level.)

The article was written on the invitation and urging of Nature editors, who wanted to present a comparison of the two draft genome sequences. They contacted George Church, professor of genetics at Harvard Medical School, as a knowledgeable player in the field of sequencing who was part of neither gene mapping team, and who was therefore able to give an informed and independent assessment.

Church and his colleagues performed a small number of computational analyses that could be applied in parallel on the two draft sequences and compared the results.

Some of these analyses -- especially the comparisons of gap sizes in the sequences -- aimed directly at comparing attributes of the two draft sequences.

Others were chosen because the researchers believed they represented the kinds of analysis that others would perform regularly on complete human genome sequences. In this latter category were an analysis of 15-base stretches that are unique in the sequences and a search for candidate binding sites of selected DNA binding proteins.

AUTHORS: George Church, professor of genetics at Harvard Medical School and John Aach, lecturer on genetics at Harvard Medical School.

PAPER: "Keeping Time with the Human Genome"

Our understanding of the mammalian circadian clock has steadily increased through the cloning and characterization of its related gene family.

By analyzing the new genome data, Steven Reppert and his research team have identified additional relatives in the "clock gene" family that may further define our knowledge of the molecular workings of the circadian clock. This knowledge could lead to the development of therapies for sleep and neuropsychiatric disorders.

AUTHORS: Steven Reppert, professor of pediatrics at Massachusetts General Hospital and Harvard Medical School.

PAPER: "Integration of Cytogenetic Landmarks into the Draft Sequence of the Human Genome"

This paper addresses an important experimental problem: How do we tie the new DNA sequence map to other positional genetic maps, such as the chromosome structure (cytogenetic) map?

In this paper, members of a research consortium mapped more than 7,500 large segments of DNA from three standard positional genetic maps to the new DNA sequence map. This integrated map is a very powerful tool for rapid localization of chromosome rearrangement breakpoints and discovery of corresponding disease genes.

The Developmental Genome Anatomy Project (the Harvard extension of the consortium) provides an example of how this strategy will work in the search to find genes important in human development and congenital anomalies.

AUTHOR: Bradley Quade, assistant professor of pathology at Brigham and Women's Hospital and Harvard Medical School.

[Contact: Courtney Humphries, John Lacey, Christine Baratta, Georgia Peirce ]

13-Feb-2001