LaDeana Hillier |
LaDeana Hillier
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Assistant Director, Genome Sequencing Center
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| Research Accomplishments & Interests |
LaDeana Hillier is an Assistant Director of the Genome Sequencing Center and Senior Research Scientist in the Department of Genetics at Washington University School of Medicine, joining the department in 1989. She has been with the Genome Sequencing Center since its inception and as Director of Informatics was finally responsible for all aspects of computational support for the lab from network design and support, to software used for all aspects of production for both mapping and sequencing (genomic and EST), to user support and education, to sequence analysis and submission of our data to public repositories, to grant preparation and publication. Her early credits related to software for PCR oligo design and sequence trace display and manipulation followed by sequence analysis of the human G6PD locus and sequence production and analysis of the model genome, C. elegans, and then large-scale EST sequencing and analysis for the human and mouse genomes and a myriad of plants and other animals.
LaDeana is an author of over 65 scientific publications including initial publications of the sequences of several genomes including C. elegans, yeast, human, mouse, chicken and chimpanzee including lead author on recent publications in Nature magazine: "The DNA sequence of human chromosome 7", "Generation and annotation of the DNA sequences of human chromosomes 2 and 4", and "Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution." She was also a featured author in Nature's Author's magazine.
LaDeana's current primary research interests are in integration of sequence and mapping data and in large-scale comparative genomic analysis.
Some details:
Following on the work on the early annotation and analysis of the C. elegans genome, LaDeana participated in an analysis effort using SAGE as a method to assess expression levels of cDNAs, where we detected changes in gene expression associated with developmental arrest and longevity in C. elegans (Jones et al., Genome Res. 2001;11:1346-52) followed by publishing a related genome, C. briggsae (Stein et al, PLoS Biol. 2003;1:E45). And now the lab is moving on to sequencing three related worms this year (C. remanei, C. japonica and CB1561) which should shed some interesting light on comparative genomics. We also did some interesting work on a bunch of related yeast strains (we participated in the finishing of the yeast genome as well (Johnston et al., Science 1994;265:2077-2081)) where we attempted to identify functional elements by comparative analysis of all of these strains (Cliften, Hillier et al., Genome Res. 2001;11:1175-86.).
In January, 1995, we received funding from Merck for the first publicly available large collection of human Expressed Sequence Tags (ESTs) which really began the flood of data into the EST public database, dbEST (http://www.ncbi.nlm.nih.gov/dbest). LaDeana developed the large-scale annotation pipeline and clustering tools as well as analyzing and publishing those data (Hillier et al., Genome Res. 1996;6:807-828) and later moved on to analyze mouse ESTs (Marra M, Hillier L, Kucaba T, et al., Nature Genetics 1999;8:191-194) as well as ESTs from many organisms (e.g. Genome Research 1998; 8:18-28)
We along with the Human Genome Sequencing Consortium announced completion of the "draft" of the human genome in June 2000 and published our findings in Nature in February 2001. For the human draft, LaDeana was responsible for software, automation, analysis, networks and systems for the lab, and in addition played a key role in the development of the physical map (the fingerprint map; McPherson, Marra, Hillier et al. Nature 2001;409:934-941) of the genome and then was responsible for the integration of the physical map and all genetic mapping data and existing sequence data to select the clones that were sequenced for the draft, attempting to maintain a non-redundant path through the genome and supplying clones to the all of the labs around the world sequencing the human genome, as well as the resulting analyses including support for the creation of the human chromosomal sequences.
Since the draft, we have moved toward actually "finishing" the human genome. Our lab has been responsible for human chromosomes 2, 4, 7, and Y, and participated in the work on other chromosomes including 14 22, and X. LaDeana was also responsible for the analyses of our chromosomes (Hillier et al., Nature 2003;424:157-164; Hillier et al., Nature, in press). Following up some of our work on human chrosomes 2, 4, and 7, we also worked on a paper studying discrepancies between all human mRNAs and their genomic regions, looking at mRNA polymorphic frameshifts, errors and RNA editing (Genome Res. 2004;14:2034-2040). We recently published a paper describing completion of the human genome (Nature 2004;431:931-945). We also participated in the human SNP consortium (Nature 2001;409:928-933) and more recently in the HAPMAP consortium (Nature 2003;426:789-96) in studying human variation.
On other larger genomes, our paper on the map (Gregory et al., Nature. 2002 Aug 15;418:743-50) and draft of the mouse genome (MGSC, Nature 2002;6915:520-562) was another great step and we are working to finish our chromosomes for the mouse genome. We also published the map of the rat genome (Kryzywinski et al., 2004;14:766-79). LaDeana recently organized and led the consortium which analyzed and published the sequence of the chicken genome (Nature 2004;432:695-716: companion papers Nature 2004;432:761-764 and Nature 2004;432:717-722). And, along with the Chimpanzee Genome Sequencing Consortium, we are currently finishing our draft sequence and analysis of the chimpanzee genome. For the chimp genome, in addition to working on the assembly of the genome from the underlying raw data, assessing those data, and other comparative primate analysis, LaDeana was also responsible for creating and assessing the alignments with the human genome, and then creating the chimpanzee chromosomal alignments and assignments. At the Genome Sequencing Center, we continue to develop new methods for sequencing and analyzing genomes.
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| Selected Publications: |
Hillier LW, Fulton RS, Fulton LA, ... Green ED, Waterston RH, Wilson, RK. The DNA sequence of human chromosome 7. Nature 2003;424:157-164.
Huang X, Wang J, Aluru S, Yang SP, Hillier L. PCAP: a whole-genome assembly program. Genome Res. 2003;13:2164-70.
Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004;431:931-945.
Hillier, LW, Miller, W, Birney, E et al. (International Chicken Genome Sequencing Consortium) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 2004;432:695-716.
Hillier, LW, Graves, TA, Fulton, RS, Fulton, LA ... Waterston, R.H., Wilson, R.K. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature (2005).
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