Ventana Medical Systems, Inc.

Georgetown University

John F Connaughton

Joseph G Utermohlen

Jeanne Dietz-Band

Wang-Ting Hsieh

Jack G Chirikjian

Gordon B Collier

The present invention provides oligonucleotide probes and oligonucleotide probe collections for detecting or localizing a plurality nucleic acid target genes within a cell or tissue sample. Specifically, the invention provides collections of oligonucleotide probes for use in in situ hybridization analyses in which each probe has a label-domain with the sequence formulas of (CTATTTT)CT, (AAAATAG)or (TTTTATC)or (GATAAAA)in which all cases 'n' would equal 1 or greater. The present invention also provides collections or 'cocktails' of oligonucleotide probes for detecting or localizing specific nucleic acid target genes within a cell or tissue sample.

Oligonucleotide sequence formula for labeling oligonucleotide probes and proteins for in-situ analysis

The present invention provides oligonucleotide probes and oligonucleotide probe collections and protein labeling for detecting or localizing a plurality nucleic acid target genes or antigens within a cell or tissue sample. Specifically, the invention provides collections of oligonucleotide probes for use in in situ hybridization analyses in which each probe has a label-domain with the sequence formulas of (CTATTTT)CT, (AAAATAG)or (TTTTATC)or (GATAAAA)in which all cases 'n' would equal 1 or greater. The present invention provides collections or 'cocktails' of oligonucleotide probes for detecting or localizing specific nucleic acid target genes within a cell or tissue sample. The cocktails are useful for detecting the following: the Kappa gene (SEQ ID NOS: 1-16 inclusive); the Lambda gene (SEQ ID NOS: 17 through 29 inclusive); the CMV (cytomegalovirus) gene (SEQ ID NOS: 30 through 50 inclusive); EBER (Epstein-Barr early RNA) gene (SEQ ID NOS: 51-54 inclusive); Alu (SEQ ID NOS: 55-56); PolyA (SEQ ID NO: 57); and the detection tail (SEQ ID NO: 58).

Oligonucleotide sequence formula for labeling olignucleotide probes and proteins for in-situ analysis

The present invention provides oligonucleotide probes and oligonucleotide probe collections and protein labeling for detecting or localizing a plurality nucleic acid target genes or antigens within a cell or tissue sample. Specifically, the invention provides collections of oligonucleotide probes for use in in situ hybridization analyses in which each probe has a label-domain with the sequence formulas of (CTATTTT)CT, (AAAATAG)or (TTTTATC)or (GATAAAA)in which all cases 'n' would equal 1 or greater. The present invention provides collections or 'cocktails' of oligonucleotide probes for detecting or localizing specific nucleic acid target genes within a cell or tissue sample. The cocktails are useful for detecting the following: the Kappa gene (SEQ ID NOS: 1-16 inclusive); the Lamba gene (SEQ ID NOS: 17 through 29 inclusive); the CMV (cytomegalovirus) gene (SEQ ID NOS: 30 through 50 inclusive); EBER (Epstein-Barr early RNA) gene (SEQ ID NOS: 51-54 inclusive); Alu (SEQ ID NOS: 55-56); PolyA (SEQ ID NO: 57); and the detection tail (SEQ ID NO: 58).

A method of detecting reciprocal gene translocations by employing multiple probe sets which span the breakpoint regions and encompass regions on both sides of each breakpoint of the translocation on each chromosome involved in the translocation. Probe sets and diagnostic kits for the method are also disclosed.

Multiple fusion probes

The invention is directed to a DNA probe set, the probe set comprising a first probe set and a second probe set, the first probe set being sufficient in length and substantially complementary to an entire breakpoint region of a first DNA and nucleotides breakpoint region but less than an entire chromosome such that the first probe set will hybridize to both sides of the breakpoint region regardless of whether the first DNA has been broken in the breakpoint region and either end fused to another DNA, and the second probe set being sufficient in length and substantially complementary to an entire breakpoint region of a second DNA and nucleotides on both sides of the breakpoint region but less than an entire chromosome such that the second probe set will hybridize to both sides of the breakpoint region regardless of whether the second DNA has been broken in the breakpoint region and either end fused to another DNA. Diagnostic kits utilizing the probe sets of the invention are also claimed.

The present invention relates to a method for cloning genes that encode restriction endonucleases by altering the level of a methyl donor co-factor of a DNA methyltransferase that protects the DNA of a host cell from damage by a restriction endonuclease. The method can be used to screen entire DNA libraries en masse to identify clones that encode restriction enzymes by growing one library replicate under high or normal methyl donor conditions to protect host DNA and a second library replicate under low methyl donor conditions allowing DNA damage from the active restriction endonuclease. Clones that encode a restriction enzyme are identified by decreased growth or color produced in response to double stranded DNA damage under the low methyl donor conditions. Colorimetric methods useful in the invention can use SOS-sensitive promoters operably linked to .beta.-galactosidase, which detect DNA damage.

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Laytonsville, MD, United States of America

John F Connaughton