Methods of determining copy number of a genetic locus

1. A method of determining in a sample, the molar ratio of a query locus to a reference locus, the method comprising:

1) forming one or more mixtures, each mixture comprising: a) a reference-query coupled probe comprising a nucleobase polymer comprising i) a probe reference locus comprising a probe reference allele, and ii) a probe query locus comprising a probe query allele, and b) a sample comprising i) a sample reference locus comprising a sample reference allele and ii) a sample query locus comprising 0 or greater copies of a sample query allele;

2) determining for each mixture a) the amount of probe reference allele as a fraction of total reference allele and b) the amount of probe query allele as a fraction of total query allele; and

3) calculating the molar ratio of the sample query allele to the sample reference allele.

2. A method in accordance with claim 1 , wherein the one or more mixtures comprises at least 2 mixtures, wherein the molar ratio of the sample reference locus to the probe reference locus of at least one first mixture does not equal the molar ratio of the sample reference locus to the probe reference locus of at least one second mixture.

3. A method in accordance with claim 1 , wherein the nucleobase polymer is a nucleic acid.

4. A method in accordance with claim 3 , wherein the nucleic acid is selected from the group consisting of a single-stranded DNA, a double-stranded DNA, a single-stranded RNA and a double-stranded RNA.

5. A method in accordance with claim 1 , wherein the sample reference allele comprises a sample reference SNP allele, the sample query allele comprises a sample query SNP allele, the probe reference allele comprises a probe reference SNP allele, and the probe query allele comprises a probe query SNP allele.

6. A method in accordance with claim 5 , wherein the determining the molar ratios comprises sequencing each locus by pyrosequencing.

7. A method in accordance with claim 1 , wherein for each mixture the molar ratio of the probe reference allele to the sample reference allele is from about 1:9 to about 9:1.

8. A method in accordance with claim 1 , wherein the sample query locus comprising a 0 or greater copies of a sample query allele is a sample query locus comprising 1 or greater copies of the sample query allele.

9. A method in accordance with claim 1 , wherein the sample comprises DNA of an animal.

10. A method in accordance with claim 9 , wherein the animal is a mammal.

11. A method in accordance with claim 10 , wherein the mammal is selected from the group consisting of a rodent, a farm animal, a companion animal, and a human.

12. A method in accordance with claim 1 , wherein the sample reference locus is a haploinsufficient locus.

13. A method in accordance with claim 1 , wherein the sample comprises genomic DNA of a transformed or transfected stem cell.

14. A reference-query coupled probe, comprising a nucleobase polymer comprising a) a reference locus comprising a probe reference allele, and b) a probe query locus comprising a probe query allele.

15. A reference-query coupled probe of claim 14 , wherein the probe reference allele comprises a probe reference SNP.

16. A reference-query coupled probe of claim 14 , wherein the probe query allele comprises a probe query SNP.

17. A reference-query coupled probe of claim 14 , wherein the probe reference allele comprises a probe reference SNP and the probe query allele comprises a probe query SNP.

18. A mixture comprising a sample and the reference-query probe of claim 14 .