التفاصيل البيبلوغرافية
| العنوان: |
Variants in Complement Regulatory Genes Predict Age-Related Macular Degeneration |
| Document Number: |
20120071356 |
| تاريخ النشر: |
March 22, 2012 |
| Appl. No: |
13/196121 |
| Application Filed: |
August 02, 2011 |
| مستخلص: |
Methods for identifying a subject at risk for developing AMD are disclosed, as are kits which can be used to practice the methods. The methods include identifying specific protective or risk polymorphisms or genotypes from the subject's genetic material, including polymorphisms in the BF, C2 and/or CFH genes. Microarrays and kits for use in these methods are also provided. |
| Inventors: |
Allikmets, Rando L. (Cornwall on Hudson, NY, US); Hageman, Gregory S. (Salt Lake City, UT, US); Dean, Michael C. (Frederick, MD, US); Gold, Albert M. (Frederick, MD, US) |
| Assignees: |
University of Iowa Research Foundation (Iowa City, IA, US), National Institutes of Health (Rockville, MD, US), The Trustees of Columbia University in The City of New York (New York, NY, US) |
| Claim: |
1. A method for assessing the risk of development of, or likely progression of, disease characterized by alternative complement cascade disregulation, including macular degeneration, in a human subject, the method comprising the steps of: i) obtaining a biological sample from a human subject; ii) analyzing the sample to determine whether the subject carries one or more of: a) A or G at rs641153 of the complement factor B (BF) gene, or R or Q at position 32 of the BF protein; b) A or T at rs4151667 of the BF gene, or L or H at position 9 of the BF protein; c) G or T at rs547154 of the C2 gene; and d) C or G at rs9332379 of the C2 gene, or E or D at position 318 of the C2 protein. |
| Claim: |
2. The method of claim 1 further comprising determining whether the subject carries one or more of: a) delTT in the complement factor H (CFH) gene; and b) C or T at rs1061170 of the CFH gene, or Y or H at position 402 of the CFH protein. |
| Claim: |
3. The method of claim 1, wherein the subject is asymptomatic of macular degeneration. |
| Claim: |
4. The method of claim 1, wherein the subject has symptoms of macular degeneration. |
| Claim: |
5. The method of claim 1, wherein the sample is an accessible body fluid. |
| Claim: |
6. The method of claim 1 comprising detecting a genotype from a cell of the subject. |
| Claim: |
7. The method of claim 1 comprising detecting a protein variant in the subject. |
| Claim: |
8. The method of claim 1 comprising detecting mRNA from a cell of the subject. |
| Claim: |
9. The method of claim 6 further comprising determining whether the subject is homozygous or heterozygous for a said polymorphism. |
| Claim: |
10. A kit for assessing the risk of development of, or likely progression of, disease characterized by alternative complement cascade disregulation, including macular degeneration, in a humans subject, the kit comprising reagents for detecting in a sample from the subject one or more of the polymorphisms or one or more of the allelic variants: a) A or G at rs641153 of the complement factor B (BF) gene, or R or Q at position 32 of the BF protein; b) A or T at rs451667 of the BF gene, or L or H at position 9 of the BF protein; c) G or T at rs547154 of the C2 gene; and, d) C or G at rs9332379 of the C2 gene, or E or D at position 318 of the C2 protein; |
| Claim: |
11. The kit of claim 10 comprising reagents for detecting in a sample from the subject one or more of the polymorphisms or one or more of the allelic variants a) delTT in the complement factor H (CFH) gene; b) C or Tat rs1061170 of the CFH gene, or Y or H at position 402 of the CFH protein. |
| Claim: |
12. The kit of claim 10 comprising reagents for detecting two or more of the polymorphisms or two or more of the allelic variants. |
| Claim: |
13. The kit of claim 10 comprising an oligonucleotide that detects a said polymorphism. |
| Claim: |
14. The kit of claim 10 further comprising reagents for amplifying a target polynucleotide sequence, wherein the target sequence comprises a said polymorphism. |
| Claim: |
15. The kit of claim 10 comprising oligonucleotides immobilized on a solid support. |
| Claim: |
16. The kit of claim 10 comprising a specific binding protein that recognizes and binds specifically to a said allelic variant. |
| Claim: |
17. A microarray comprising oligonucleotide probes capable of hybridizing under stringent conditions to one or more nucleic acid molecules having a protective polymorphism selected from the group consisting of: a) R32Q in BF (rs641153); b) L9H in BF (rs4151667); c) IVS 10 in C2 (rs547154); and, d) E318D in C2 (rs9332739). |
| Claim: |
18. The microarray of claim 17, further comprising oligonucleotide probes capable of hybridizing under stringent conditions to one or more nucleic acid molecules having a polymorphism selected from the group consisting of: a) the delTT polymorphism in CFH; b) the R150R polymorphism in BF; and, c) the Y402H polymorphism in CFH. |
| Current U.S. Class: |
506/16 |
| Current International Class: |
40; 01; 01; 12 |
| رقم الانضمام: |
edspap.20120071356 |
| قاعدة البيانات: |
USPTO Patent Applications |