Genetic polymorphisms associated with Alzheimer's Disease, methods of detection and uses thereof
View Patent ↗The present invention is based on the discovery of genetic polymorphisms that are associated with Alzheimer's Disease. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.
1. A method of determining whether a human has an increased risk for late onset Alzheimer's disease, comprising testing nucleic acid from said human to determine the nucleotide content at polymorphism rs4878104 in gene DAPK1, and determining that said human has an increased risk for late onset Alzheimer's disease if said human has C or G at rs4878104, wherein said increased risk for late onset Alzheimer's disease is relative to being homozygous for T or A at rs4878104.
2. A method of determining whether a human has a decreased risk for late onset Alzheimer's disease, comprising testing nucleic acid from said human to determine the nucleotide content at polymorphism rs4878104 in gene DAPK1, and determining that said human has a decreased risk for late onset Alzheimer's disease if said human is homozygous for T or A at rs4878104, wherein said decreased risk for late onset Alzheimer's disease is relative to having C or G at rs4878104.
3. The method of claim 1 , wherein said polymorphism rs4878104 is at position 101 of SEQ ID NO: 28 or its complement.
4. The method of claim 2 , wherein said polymorphism rs4878104 is at position 101 of SEQ ID NO: 28 or its complement.
5. The method of claim 3 , wherein the presence of C at position 101 of SEQ ID NO: 28 or G at position 101 of its complement indicates said human has an increased risk for late onset Alzheimer's disease, relative to being homozygous for T at position 101 of SEQ ID NO: 28 or A at position 101 of its complement.
6. The method of claim 4 , wherein said human who is homozygous for T at position 101 of SEQ ID NO: 28 or A at position 101 of its complement has a decreased risk for late onset Alzheimer's disease, relative to having C at position 101 of SEQ ID NO: 28 or G at position 101 of its complement.
7. The method of claim 1 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human.
8. The method of claim 2 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human.
9. The method of claim 7 , wherein said biological sample is blood, saliva, or buccal cells.
10. The method of claim 8 , wherein said biological sample is blood, saliva, or buccal cells.
11. The method of claim 7 , further comprising preparing said nucleic acid extract from said biological sample prior to said testing step.
12. The method of claim 8 , further comprising preparing said nucleic acid extract from said biological sample prior to said testing step.
13. The method of claim 11 , further comprising obtaining said biological sample from said human prior to said preparing step.
14. The method of claim 12 , further comprising obtaining said biological sample from said human prior to said preparing step.
15. The method of claim 1 , wherein said testing step comprises nucleic acid amplification.
16. The method of claim 2 , wherein said testing step comprises nucleic acid amplification.
17. The method of claim 15 , wherein said nucleic acid amplification is carried out by polymerase chain reaction.
18. The method of claim 16 , wherein said nucleic acid amplification is carried out by polymerase chain reaction.
19. The method of claim 1 , wherein the step of determining that said human has said increased risk is performed by computer software.
20. The method of claim 5 , wherein the step of determining that said human has said increased risk is performed by computer software.
21. The method of claim 2 , wherein the step of determining that said human has said decreased risk is performed by computer software.
22. The method of claim 6 , wherein the step of determining that said human has said decreased risk is performed by computer software.
23. The method of claim 1 , wherein said testing is performed using sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, single-stranded conformation polymorphism analysis, or denaturing gradient gel electrophoresis (DGGE).
24. The method of claim 2 , wherein said testing is performed using sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, single-stranded conformation polymorphism analysis, or denaturing gradient gel electrophoresis (DGGE).
25. The method of claim 1 , wherein said testing is performed using an allele-specific method.
26. The method of claim 2 , wherein said testing is performed using an allele-specific method.
27. The method of claim 25 , wherein said allele-specific method is allele-specific probe hybridization, allele-specific primer extension, or allele-specific amplification.
28. The method of claim 26 , wherein said allele-specific method is allele-specific probe hybridization, allele-specific primer extension, or allele-specific amplification.
29. The method of claim 25 , wherein said allele-specific method detects said C or said G.
30. The method of claim 26 , wherein said allele-specific method detects said T or said A.
31. The method of claim 1 which is an automated method.
32. The method of claim 2 which is an automated method.
33. The method of claim 1 , wherein said human is homozygous for said C or said G.
34. The method of claim 5 , wherein said human is homozygous for said C or said G.
35. The method of claim 1 , wherein said human is heterozygous for said C or said G.
36. The method of claim 5 , wherein said human is heterozygous for said C or said G.