Expression profiles in adult and fetal organs

• US 6,033,860 A
• Filed: 10/30/1998
• Issued: 03/07/2000
• Est. Priority Date: 10/31/1997
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Warrington, Janet A., Nair, Archana, Lockhart, David J.
• Primary Examiner(s): KETTER, JAMES S
• Application Number:
  US09/182,991
• Time in Patent Office: 494 Days
• Field of Search: 435/6, 536/24.31
• US Class Current: 435/6.16
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6881 for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Expression profiles have been constructed for liver and brain, in adult and fetal and adolescent tissue. These provide the art with probes which are highly differentially expressed among stages and organs. The profiles and probes can be used to prioritize potential drug targets, to monitor disease progression and remission, and to assess drug metabolism. Solid supports are also provided which facilitate these uses.

Claims

1. A method of screening a drug for deleterious side effects on a cell comprising the steps of:

assaying for the amount of expression in the cell of two or more genes selected from the group consisting of;

G6PD, calcium channel, synaptotagamin, neuromodulin, calmodulin, nicotinic acetylcholine receptor beta 2, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, cytochrome p450-2E1, and thymosin beta-10, wherein the expression in the cell is assayed before and after the cell has been contacted with the drug, wherein alteration of the amount of expression of at least one of these genes by the drug is indicative of a deleterious side effect.

6. The method of claim 1, 2, 3, 4, or 5, wherein expression of at least 3 genes are assayed.

7. The method of claim 1, 2, 4, or 5, wherein expression of at least 4 genes are assayed.

8. The method of claim 1, 2, 4, or 5, wherein expression of at least 5 genes are assayed.

9. The method of claim 1, 2, 4, or 5, wherein expression of at least 6 genes are assayed.

10. The method of claim 1, 2, 4, or 5, wherein expression of at least 7 genes are assayed.

11. The method of claim 1, 2, 4, or 5, wherein expression of at least 8 genes are assayed.

12. The method of claim 1, 2, 4, or 5, wherein expression of at least 9 genes are assayed.

13. The method of claim 1, 4, or 5, wherein expression of at least 10 genes are assayed.

2. A method of distinguishing between a fetal and an adult liver sample comprising the steps of:

assaying for expression in the sample of two or more genes selected from the group consisting of;

G6PD, calmodulin, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, hepatocyte gf, IGF binding protein 1, ubiquitin, cytochrome p450-2E1, and thymosin beta-10, wherein expression of G6PD, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, cytochrome p450-2E1, and thymosin beta-10 are indicative of an adult liver, and expression of calmodulin, hepatocyte gf IGF binding protein 1, and ubiquitin are indicative of a fetal liver.

3. A method of distinguishing between a fetal and adult brain tissue, comprising the steps of:

assaying for expression in the tissue of two or more genes selected from the group consisting of;

nicotinic acetylcholine receptor beta 2, ubiquitin, and thymosin beta-10, wherein expression of nicotinic acetylcholine receptor beta 2 or ubiquitin indicates an adult brain.

4. A method of determining the source of a tissue as adult brain or adult liver, comprising the steps of:

assaying for expression in the tissue of two or more genes selected from the group consisting of;

calcium channel, synaptotagamin, neuromodulin, calmodulin, nicotinic acetylcholine receptor beta 2, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, and cytochrome p450-2E1, wherein expression of calcium channel, synaptotagamin, neuromodulin, calmodulin, nicotinic acetylcholine receptor beta 2, ubiquitin, or bone morphogenetic protein precursor indicates a brain source for the tissue, and wherein expression of pyruvate dehydrogenase E1, VLDLR, udulin1/undulin/extracellular matrix glycoprolein, apolipoprotein B100, thymosin beta-10, hepatocyte gf, IGF binding protein 1, or cytochrome p450-E1 indicates a liver source for the tissue.

5. A method of distinguishing a tissue source as fetal brain or fetal liver, comprising the steps of:

assaying for expression in the tissue of two or more genes selected from the group consisting;

of;

G6PD, calcium channel, synaptotagamin, neuromodulin, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, and thymosin beta-10, wherein expression of G6PD, calcium channel, synaptotagamin, neuromodulin, thymosin beta-10 or bone morphogenetic protein precursor indicates a fetal brain source and expression of pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, indicates a fetal liver source.

14. A solid support for screening a drug for deleterious side effects on a cell comprising:

at least two oligonucleotides for probing two or more genes selected from the group consisting of;

G6PD, calcium channel, synaptotagamin, neuromodulin, calmodulin, nicotinic acetylcholine receptor beta 2, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, cytochrome p450-2E1, and thymosin beta-10, wherein each oligonucleotide comprises a sequence which is complementary to one of the two or more genes.

19. The solid support of claim 14, 15, 16, 17, or 18 which is an array comprising at least 10 different oligonucleotides in discrete locations per cm².

20. The solid support of claim 14, 15, 16, 17, or 18 which is an array comprising at least 100 different oligonucleotides in discrete locations per cm².

21. The solid support of claim 14, 15, 16, 17, or 18 which is an array comprising at least 1,000 different oligonucleotides in discrete locations per cm².

22. The solid support of claim 14, 15, 16, 17, or 18 which is an array comprising at least 10,000 different oligonucleotides in discrete locations per cm².

15. A solid support for distinguishing between a fetal and an adult liver sample comprising:

two or more oligonucleotides for detecting two or more genes selected from the group consisting of;

G6PD, calmodulin, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, hepatocyte gf, IGF binding protein 1, ubiquitin, cytochrome p450-2E1, and thymosin beta-10 wherein each oligonucleotide comprises a sequence which is complementary to one of the two or more genes.

16. A solid support for distinguishing between a fetal and adult brain tissue, comprising:

two more oligonucleotides for detecting two or more genes selected from the group consisting of;

nicotinic acetylcholine receptor beta 2, ubiquitin, and thymosin beta-10, wherein each oligonucleotide comprises a sequence which is complementary to one of the two or more genes.

17. A solid support for determining the source of a tissue as adult brain or adult liver, comprising:

two or more oligonucleotides for detecting two or more genes selected from the group consisting of;

calcium channel, synaptotagamin, neuromodulin, calmodulin, nicotinic acetylcholine receptor beta 2, VLDLR, udulin1/undulin/extracellular matrix glycoprotein, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, and cytochrome p450-2E1, wherein each oligonucleotide comprises a sequence which is complementary to one of the two or more genes.

18. A solid support for distinguishing a tissue source as fetal brain or fetal liver, comprising:

two or more oligonucleotides for detecting two or more genes selected from the group consisting of;

G6PD, calcium channel, synaptotagamin, neuromodulin, pyruvate dehydrogenase E1, apolipoprotein B100, hepatocyte gf, IGF binding protein 1, ubiquitin, bone morphogenetic protein precursor, and thymosin beta-10, wherein each oligonucleotide comprises a sequence which is complementary to one of the two or more genes.