The Crown Human Genome Center
Doron Lancet, Director
The Ralph D. and Lois R. Silver Professorial Chair of Human Genomics
The center was inaugurated in 1998 in order to advance genome research at the Weizmann Institute. The center addresses the challenges posed by the enormous worldwide progress in DNA sequencing of numerous genomes.In 2008 the Crown Center initiated and introduced the novel Illumina (Solexa) high-throughput DNA sequencing technology to the Department of Biological Services, thus, once again, providing Weizmann scientists with the most advanced genome facilities world wide. This revolutionary technology enables various applications, including bacterial whole genome sequencing, whole genome scale gene expression, Transcriptome and miRNA sequencing, as well as identification of regulatory elements based on Chromatin Immuno-Precipitation analyses, in a most efficient and cost effective manner. In the coming year The Crown Center will also continue to support WIS users of this novel technology In previous years, the Crown Center helped introduce the following infrastructure activities that are continuously available for WIS scientists: 1) Large scale DNA sequencing of genomic segments. 2) DNA microarray technologies, including an Affymetrix instrument with photolithography-generated oligonucleotide arrays, which analyses mRNAs expression patterns or genomic mutations in thousands of genes from different species. In this scope, the GeneNote project, supported by the Abraham and Judith Goldwasser fund elucidated basic patterns of gene expression in human tissues over the entire genomic gamut of ~40,000 genes. 3) Computational genomics, including know-how on the utilization of the complete, diversely annotated human genome sequence, as well as other completed genomes, in terms of genomic maps and gene repositories. This includes access to external databases and internal data structures such as GeneCards and its affiliated databases (http://www.genecards.org/). Most recently, the GeneALaCart and GeneDecks facilities are being developed to enlarge the scope of GeneCards and exploit its wealth of annotations by providing batch queries and sophisticated analysis tools on sets of genes (e.g. those that result from the output of high throughput experiments). In the past, gene discovery projects, performed in collaboration with medical establishments throughout Israel, have led to the discovery of 7 novel genes that underlie human inherited diseases typical to Israeli ethnic groups, and are now available for genetic consultation. The Sequenom MassArray system for discovering and scoring human genetic variations (Single Nucleotide Polymorphisms - SNPs) is very successful. This technology is a central topic of genomic research, aimed at understanding variations among individuals within a species. Nearly thirty collaborative projects aimed at understanding how small genetic variations culminate in causing diseases, from cancer to schizophrenia, were carried out, six of which are ongoing. Pharmacogentic studies, as well as agricultural studies mapping quantitative traits loci were successfully carried out. All of these studies were concluded, and reported on in a variety of scientific publications. With the discovery of CNVs (Copy Number Variation) a year ago, a whole new vista of genetic variation, with dramatic implications for disease studies, has been revealed. In line with this discovery, the Crown Center initiated a study to identify CNVs in association with specific anosmia. The Center also harbors a program in evolutionary genomics, including the evolution of the sense of smell, whereby novel information on extreme genetic diversity has been uncovered, relevant to the fragrance and flavor industry. An important example of the olfaction evolution is the recent analysis of the platypus genome, performed at the center, that discovered an olfactory receptor (OR) repertoire of 700 genes. This repertoire is roughly half as large as that in a typical mammal, suggesting that monotremes serve as a departure point for the OR repertoire expansion in mammals, potentially via a duplication of the entire OR sub-genome around the monotreme-marsupial separation. Also, a program in prebiotic evolution is ongoing, aiming at solving one of the most important open questions of science: how life evolved on planet earth. Such computer-based early evolution studies focus on developing a model (The Graded Autocatalysis Replication Domain, GARD) which is an analogy to biochemical networks, with many of the realistic kinetic and thermodynamic properties of present-day cellular networks. More recently, the Synlet (Synthetic Lethality) project has been initiated. The purpose of this project is to develop methodologies which will predict synthetic lethality within the GARD network. We will then apply these methodologies on the yeast and human protein interaction networks. This is one of many efforts within the new realm of Systems Biology, and the Genome Center is thus in close interaction with the newly inaugurated Center for Systems Biology at Weizmann, directed by Prof. Eytan Domany. The Crown Human Genome Center receives current support from the Crown Family and the Israel Science Foundation Grant - Sub-Contract of Hadassah Medical Center. Past support was received from the Israel ministry of Science and Technology (National Knowledge Center for Genomics), a Magneton project of the Ministry of Industry and Trade, the Abraham and Judy Goldwasser Fund, Israel Science Foundation Grant - Sub-Contract of Hadassah Medical Center and Philip Morris External Research Program, and lately, an Israel Science Foundation equipment grant.