The Salk Institute for Biological Studies

Other

Egea Biosciences, Inc.

University of Texas System

Johnson & Johnson Gmbh

Janssen Biotech, Inc.

Glen A Evans

Licia Selleri

Gopalan Raghunathan

Katya McLane

Gary G Hermanson

Jia Li

Liying Huang

Pauline Parry

Malek Djabali

Edward D Esplin

Michael W Smith

James H Eubanks

Steven Siqing Wang

The present invention outlines a novel approach to utilizing the results of genomic sequence information by computer-directed polynucleotide assembly based upon information available in databases such as the human genome database. Specifically, the present invention may be used to select, synthesize and assemble a novel, synthetic target polynucleotide sequence encoding a target polypeptide. The target polynucleotide may encode a target polypeptide that exhibits enhanced or altered biological activity as compared to a model polypeptide encoded by a natural (wild-type) or model polynucleotide sequence.

Computer-directed assembly of a polynucleotide encoding a target polypeptide

Novel TNF&#x3b1; antibody polypeptides and nucleic acids are disclosed. Methods of utilizing the polypeptides to treat TNF&#x3b1;-related diseases are also disclosed.

Anti-TNF&#x3b1; antibodies and methods of use

Anti-TNF&#x3b1; antibodies

The present invention identifies the PPP2R1B gene, as a human tumor suppressor gene. Sequencing of the PPP2R1B revealed that the gene is located on human chromosome 11q22-24 and that gene were mutated in tumors and tumor cell lines, leading to the classification of this gene as a tumor suppressor. Further analyses have demonstrated the presence of a number of mutations in the gene in lung, colon, breast and cervical cancer cells. Methods for diagnosing and treating cancers related to this tumor suppressor also are disclosed.

PPP2R1B is a tumor suppressor

The present invention provides a novel approach to utilizing the results of genomic sequence information by computer-directed polynucleotide assembly based upon information available in databases such as the human genome database. Specifically, the present invention can be used to select, synthesize and assemble a novel, synthetic target polynucleotide sequence encoding a target polypeptide. The target polynucleotide can encode a target polypeptide that exhibits enhanced or altered biological activity as compared to a model polypeptide encoded by a natural (wild-type) or model polynucleotide sequence.

Method for assembly of a polynucleotide encoding a target polypeptide

The present invention relates generally to the fields of oligonucleotide synthesis. More particularly, it concerns the assembly of genes and genomes of completely synthetic artificial organisms. Thus, the present invention outlines a novel approach to utilizing the results of genomic sequence information by computer directed gene synthesis based on computing on the human genome database. Specifically, the present invention contemplates and describes the chemical synthesis and resynthesis of genes defined by the genome sequence in a host vector and transfer and expression of these sequences into suitable hosts.

Method for the complete chemical synthesis and assembly of genes and genomes

In accordance with the present invention, there is provided an isolated peptide having the characteristics of human trithorax protein (as well as DNA encoding same, antisense DNA derived therefrom and antagonists therefor). The invention peptide is characterized by having a DNA binding domain comprising multiple zinc fingers and at least 40% amino acid identity with respect to the DNA binding domain of,protein and at least 70% conserved sequence with respect to the DNA binding domain of,protein, and wherein said peptide is encoded by a gene located at chromosome 11 of the human genome at q23. Also provided are methods for the treatment of subject(s) suffering from immunodeficiency, developmental abnormality, inherited disease, or cancer by administering to said subject a therapeutically effective amount of one of the above-described agents (i.e., peptide, antagonist therefor, DNA encoding said peptide or antisense DNA derived therefrom). Also provided is a method for the diagnosis, in a subject, of immunodeficiency, developmental abnormality, inherited disease, or cancer associated with disruption of chromosome 11 at q23.

Nucleic acids encoding human trithorax protein

Nucleotide sequence defining a polymorphic locus useful for identification of an individual. Also disclosed are oligonucleotide primers useful in amplification of the locus and methods for detecting the amplified locus.

Polymorphic locus

The present invention relates to a rapid and powerful sequence 'sequence sampled mapping' method for sequencing complex genomes. The invention method is applicable to genomic DNA, preferably mammalian chromosomes, and in a preferred embodiment, employs a 'bottom-up' mapping strategy, which allows for the simultaneous analysis of multiple cosmid clones for the detection of overlaps. The sequence sample mapping method is useful first, for the completion of high density sequence-based maps, and ultimately, for the complete sequencing of genomic DNA directly from cosmid clones.

Method for generation of sequence sampled maps of complex genomes

Methods for identifying the existence, and optionally the location, of chromosomal aberration(s) in the genome of an organism are disclosed. Intact, chromosomal DNA is hybridized with one or more clones constructed from chromosomal DNA derived from an organism of the same species as the organism to be tested. By identifying the existence of a chromosomal aberration, the susceptibility of an individual to certain disease states can be predicted, and/or the nature of a given disease state can be ascertained with greater certainty.

Analytical methods and probes for the identification of chromosomal

Method for simultaneous identification of overlapping cosmid clones among multiple cosmid clones and the use of the method for mapping complex genomes are provided. A library of cosmid clones that contains the DNA to be mapped is constructed and arranged in a manner such that individual clones can be identified and replicas of the arranged clones prepared. In preferred embodiments, the clones are arranged in a two dimensional matrix. In such embodiments, the cosmid clones in a row are pooled, mixed probes complementary to the ends of the DNA inserts int he pooled clones are synthesized, hybridized to a first replica of the library. Hybridizing clones, which include the pooled row, are identified. A second portion of clones is prepared by pooling cosmid clones that correspond to a column in the matrix. The second pool thereby includes one clone from the first portion pooled clones. This common clone is located on the replica at the intersection of the column and row. Mixed probes complementary to the ends of the DNA inserts in the second pooled portion of clones are prepared and hybridized to a second replica of the library. The hybridization pattern on the first and second replicas of the library are compared and cross-hybridizing clones, other than the clones in the pooled column and row, that hybridize to identical clones in the first and second replicas are identified. These clones necessarily include DNA inserts that overlap with the DNA insert int he common clone located at the intersection of the pooled row and pooled column. The DNA in the entire library may be mapped by pooling the clones in each of the rows and columns of the matrix, preparing mixed end-specific probes and hybridizing the probes from each row or column to a replica of the library. Since all clones in the library are located at the intersection of a column and a row, the overlapping clones for all clones in the library may be identified and a physical map constructed. In other preferred embodiments, the cosmid clones are arranged in a three dimensional matrix, pooled and compared in threes according to intersecting planes of the three dimensional matrix. Arrangements corresponding to geometries of higher dimensions may also be prepared and used to simultaneously identify overlapping clones in highly complex libraries with relatively few hybridization reactions.

Growing community of inventors

San Marcos, CA, United States of America

Glen A Evans