Boguski Genome Research

markboguski.net

Home Education Employment Publications Presentations Boards Teaching Awards

Genome Research

The Nucleotide and Derived Amino Acid Sequence of Human Apolipoprotein A-IV mRNA and the Close Linkage of Its Gene to the Genes of Apolipoproteins A-I and C-III (1986) |PubMed|PDF|
Structure and Expression of the Human Apolipoprotein A-IV Gene (1987) |PubMed|PDF|
Establishing a Human Transcript Map (1995) |PubMed|PDF| This paper introducted the concept of "UniGenes" and provided a resource that directly let to the first large-scale transcript map of the human genome (pictured at right) and described in the next paper.
A Gene Map of the Human Genome (1996) |PubMed|PDF| Historically speaking, this was the first instance of Science magazine using the World Wide Web to publish results, provide hyper-linked information resources and supplemental data sets. This map facilitated and accelerated the positional cloning of hundreds of genes and this transcript mapping approach was widely applied to other organisms.
Genome Maps 7. The Human Transcript Map. Wall Chart (1996) |PubMed|Chart|
An STS-Based Map of the Human Genome (1996)
A Physical Map of 30,000 Human Genes (1998) |PubMed|PDF|web site| This paper in Science represented an update of Gene Map '96. At this time it was still estimated that the human genome contained between 50,000 and 100,000 genes. Now that we know that there are only about 20,000 human genes, this '98 Gene Map was more comprehensive than we could have imagined at the time.
A YAC-Based Physical Map of the Mouse Genome (1999) |PubMed|PDF|
Frequent Human Genomic DNA Transduction Driven by Line-1 Retrotransposition (2000) |PubMed|PDF|
Experimental Annotation of the Human Genome Using Microarray Technology (2001) |PubMed|PDF| Despite the great success of bioinformatics and computational biology during the past 15 years, I had long believed that the most powerful approach to biomedical research problems is not through computational methods alone, nor is it through experimental methods alone, but rather via a synergistic fusion of the two approaches. This paper substantiates this view and was published in the February 2001 Genome Issue of Nature, directly following the historic publication describing the initial sequencing and analysis of the human genome (Lander et al., 2001). Why this juxtaposition? Because, as Lander and colleagues point out in their section on “Gene content of the human genome,” computer programs for gene prediction have only limited accuracy and direct, experimental evidence of transcription is needed to validate, refine, correct or refute such predictions. Our paper describes both conceptual and technological advances in the analysis of gene activity on a genome scale. Up until this point in time, microarrays were widely but exclusively used for gene expression profiling and genotyping and both of these applications depended upon prior knowledge of expressed transcripts or sequence polymorphisms, respectively. Our work showed that it was technically feasible to design arrays containing probes to every predicted, hypothetical exon in the human genome and then use these “exon arrays” to simultaneously assess the reality of predicted exons and examine differential splicing in mRNA transcripts under different conditions and in different tissue contexts. Exon arrays still depend upon algorithmic exon predictions, although one can afford to greatly reduce the stringency of the predictions to include all potential true positives because our approach is unaffected by large numbers of false positives. Nevertheless, gene prediction algorithms, even at low stringency, might miss transcription units they were not designed to detect. Therefore, we went on to show in this paper that one could probe the genome for gene activity in a completely unbiased fashion using “tiling arrays” of overlapping oligonucleotide probes representing both strands of genomic DNA to completely eliminate the need for any a priori information on which parts of the genome might be expressed. We demonstrated the potential of tiling arrays on an entire human chromosome. Our approaches to experimental gene validation described in this paper have been widely applied to other genomes and have also stimulated the development of new algorithms and statistical tools for both the design of arrays and analysis of the derived data.
Molecular Archeology of L1 Insertions in the Human Genome (2002) |PubMed|PDF|

Home Education Employment Publications Presentations Boards Teaching Awards

In the 1990s, the journal Science published an annual Genome Issue containing a fold-out poster representing highlights of the Human Genome Project that year. 1996 was the first year that the poster was also a web site built by Greg Schuler and I, working the Barbara Jansy, the editor of Science. This transcript map of the human genome was updated in 1998.