Gene expression profiles that identify genetically elite ungulate mammals

• US 20050137805A1
• Filed: 05/27/2004
• Published: 06/23/2005
• Est. Priority Date: 05/30/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Everts, Robin E., Lewin, Harris A., Rodriguez-Zas, Sandra, Liu, Zonglin
• Granted Patent: US 7,638,275 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• 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 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 1/6888 for detection or identification of organisms
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Genetically elite ungulate mammals are identified on the basis of gene expression profiles from biological samples such as liver and blood. Methods and compositions are presented to select genetically elite animals with a desired phenotype such as high milk production for breeding to improve production levels. A method to select an animal with a specific phenotype, e.g. milk production and health traits, includes creating a Gene Expression Index for a specific phenotype and using the index to identify candidate animals for breeding by comparing the index to gene expression profiles of the animals.

Claims

1. A method of constructing a Gene Expression Index for phenomic selection of a phenotype of an ungulate mammal, the method comprising:

(a) selecting ungulate mammals with specific levels of the phenotype;

(b) selecting a plurality of genes for which expression can be determined;

(c) comparing expression levels of the plurality of genes in ungulate mammals at each level of the phenotype; and

(d) determining a set of genes predictive of a specific phenotype level to create the Gene Expression Index.

2. A method of constructing a Reference Expression Profile of an ungulate mammal, the method comprising:

(a) selecting an optimal subset from the Gene Expression Index of claim 1 that accounts for a significant fraction of the variation in the phenotype;

(b) determining a gene expression profile of the ungulate mammal for the optimal subset; and

(c) designating the gene expression profile as a Reference Expression Profile.

3. A method of determining whether an ungulate mammal is genetically elite for a phenotype of interest, the method comprising:

(a) determining a gene expression profile for the ungulate mammal;

(b) comparing the gene expression profile with the Gene Expression Index of claim 1 for the phenotype of interest; and

(c) designating the ungulate mammal as elite if the gene expression profile is correlated with the Gene Expression Index.

4. The method of claim 1, wherein the plurality of genes are selected from the group consisting of nucleotide sequences designated by GenBank accession numbers listed in TABLE I, II, and III.

6. The method of claim 4, further comprising correlating gene expression values of the male of female cattle with a Reference Expression Profile, which is obtained from an optimal subset of the Gene Expression Index.

7. The method of claim 6, wherein the subset is about one to one hundred genes.

9. The method of claim 7, wherein the subset comprises genes designated by GenBank accession numbers AW461980, AW464526, AW465165, AW465571, AW466043, BF039168, BF044446, BF044893, BF046007, BF046202, BF440243, BF440261, AW466044, and BF039212.

12. The method of claim 6, wherein the optimal subset genes compromise ranked in the Gene Expression Index by statistical methods.

5. A method for selecting male or female cattle as genetically elite for milk production, the method comprising:

(a) constructing a Gene Expression Index comprising gene sequences designated by GenBank accession numbers listed in TABLE I, II, and III;

(b) determining a gene expression profile for the cattle; and

(c) designating the male or female cattle as genetically elite if their gene -expression profiles are correlated with the gene expression values in the Gene Expression Index.

10. The method of claim 5, wherein the gene expression profile is obtained by a microarray analysis.

11. The method of claim 5, wherein the gene expression profile is obtained by a quantitative polymerase chain reaction analysis.

8. A method for selecting male or female cattle as genetically elite for milk production, the method comprising:

(a) creating a Reference Expression Profile, wherein the Reference Expression Profile accounts for a significant fraction of the variation in milk production; and

(b) designating the male or female cattle as genetically elite if their gene expression profiles are correlated with the gene expression values in the Reference Expression Profile.

13. A microarray comprising nucleic acids comprising sequences designated by GenBank accession numbers listed in TABLES I or II or III or a combination thereof.

14. A Gene Expression Index comprising genes whose GenBank accession numbers are in Table I, Table II, Table III or a combination thereof.

15. The Gene Expression Index of claim 14 further comprising an optimal subset of about 1 to about 100 genes, said subset designating a Reference Expression Profile.

16. The Gene Expression Index of claim 14, wherein the optimal subset comprises genes designated by GenBank accession numbers AW461980, AW464526, AW465165, AW465571, AW466043, BF039168, BF044446, BF044893, BF046007, BF046202, BF440243, BF440261, AW466044, and BF039212.

17. The Gene Expression Index of claim 14, wherein the optimal subset comprises genes designated by GenBank accession numbers AW466043, BF044446, BF039168, BF046202, and AW461980.

18. A method for predicting milk production in a candidate cow, the method comprising:

(a) obtaining a candidate gene expression profile of the candidate cow; and

(b) comparing the candidate gene expression profile to a Gene Expression Index from cows with known milk production levels.

19. A method for predicting milk production in the daughters of a candidate bull, the method comprising:

(a) obtaining a candidate gene expression profile of the candidate bull; and

(b) comparing the candidate gene expression profile to a Gene Expression Index from bulls whose daughters have known milk production levels.

20. A method of increasing milk production in cattle, the method comprising:

(a) selecting a nucleic acid sequence whose GenBank accession number is listed in TABLE I, II or III; and

(b) modulating expression of the gene in the cattle to increase milk production by pharmaceutical or transgenic means.

21. A kit for determining if an ungulate mammal is genetically elite for milk production, the kit comprising:

(a) reagents for determining a gene expression profile in a biological sample from the ungulate mammal; and

(b) a Reference Expression Profile to which the gene expression profile is compared.

22. The kit of claim 21 further comprising a computer program to determine if the ungulate mammal is elite by comparing the gene expression profile to the Reference Expression Profile.

23. The kit of claim 21, wherein the reagents comprise genes selected from the group consisting of cDNA, oligonucleotides, and primers to amplify a subset of genes whose sequences are designated by GenBank accession numbers listed in TABLE I, II or III.

24. The kit of claim 23, wherein the genes are designated by GenBank accession numbers AW461980, AW464526, AW465165, AW465571, AW466043, BF039168, BF044446, BF044893, BF046007, BF046202, BF440243, BF440261, AW466044, and BF039212.

25. The kit of claim 21, wherein the reagents are on a microchip.

26. A microarray comprising genes designated by GenBank accession numbers AW461980, AW464526, AW465165, AW465571, AW466043, BF039168, BF044446, BF044893, BF046007, BF046202, BF440243, BF440261, AW466044, and BF039212.

27. A microarray comprising genes designated by GenBank accession numbers AW466043, BF044446, BF039168, BF046202, and AW461980.

28. A polynucleotide selected from the group consisting of sequences designated by SEQ ID NOS:

13, 26, 50, 56, 58, 61, 71, 72, 111, 123, 127, 129, 139, 149, 156, 166, 185, 195, 199, 217, 252, 253, 255, 268, 275, 296, 304, 306, 315, 339, 358 and 400.