(WO202051530) Methods of using genetic markers associated with endometriosis 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(WO202051530) Methods of using genetic markers associated with endometriosis
公开号/公开日
WO2020/051530 / 2020-03-12
申请号/申请日
WOUS2019/050061 / 2019-09-06
发明人
ALBERTSEN HANSCHETTIER RAKESH NWARD KENNETHARGYLE VEEANN;
申请人
JENU BIOSCIENCES;
主分类号
IPC分类号
C07H-021/04 C12Q-001/68 C12Q-001/6876
摘要
(WO2020/051530) Disclosed herein are methods of using genetic markers associated with endometriosis, for example via a computer-implemented program to predict risk of developing endometriosis, and methods of preventing or treating endometriosis or a symptom thereof.
机翻摘要
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地址
代理人
(WO202051530) ARONIN, Caren P. ([US])
代理机构
;
优先权号
2018US-62728263 2018US-62741434 2018US-62741437 2018US-62741439 2018US-62741805 2018US-62741807
主权利要求
(WO2020/051530) CLAIMS WHAT IS CLAIMED: 1. A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting one or more genetic variants in said nucleic acid sample, wherein said one or more genetic variants are listed in Table 1, Table 2 or Table 3. 2. The method of claim 1, wherein said high throughput method comprises nanopore   sequencing. 3. The method of claim 1 or 2, wherein said nucleic acid sample comprises RNA. 4. The method of claim 3, wherein said RNA comprises mRNA. 5. The method of claim 1 or 2, wherein said nucleic acid sample comprises DNA. 6. The method of claim 5, wherein said DNA comprises cDNA, genomic DNA, sheared DNA, cell free DNA, fragmented DNA, or PCR amplified products produced therefrom, or any combination thereof. 7. The method of claim 5, wherein said DNA comprises DNA from an endometriosis lesion or peritoneal fluid. 8. The method of any one of claims 1-7, wherein said one or more genetic variants comprise a genetic variant defining a minor allele. 9. The method of any one of claims 1-7, wherein said one or more genetic variants comprise at least about: 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 500, or more genetic variants defining minor alleles. 10. The method of any one of claims 1-9, wherein detection of said one or more genetic variants has an odds ratio (OR) for endometriosis of at least about: 1.5, 2, 5, 10, 20, 50, 100, or more. 11. The method of any one of claims 1-10, wherein said one or more genetic variants comprise a synonymous mutation, a non-synonymous mutation, a stop-gain mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. 12. The method of any one of claims 1-11, wherein said one or more genetic variants comprise a protein damaging mutation. 13. The method of any one of claims 12, wherein said one or more genetic variants further   comprise a protein damaging or loss of function variant in one or more genes selected from the group consisting of GAT2, CCDC169, CASP8AP2, POU2F3, CD 19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR, and any combinations thereof. 14. The method of any one of claims 1-12, wherein said one or more genetic variants are comprised in GAT2, CCDC169, CASP8AP2, POU2F3, CD 19, IGSF3, GLI3, PEX26, OLIG3, CIB4, NKX3-2, CFTR or a combination thereof 15. The method of any one of claims 1-13, further comprising detecting one or more additional variants defining a minor allele listed in Table 4. 16. The method of any one of claim 1-15, wherein said one or more genetic variants are   identified or weighted based on a predictive mathematical or computer programmed algorithm. 17. The method of any one of claims 1-16, wherein said one or more genetic variants are   identified based on reference to a database. 18. The method of any one of claims 1-17, further comprising identifying said subject as having endometriosis or being at risk of developing endometriosis. 19. The method of claim 18, wherein said identifying said subject as having endometriosis or being at risk of developing endometriosis is with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 20. The method of any one of claims 18-19, wherein said identifying said subject as having   endometriosis or being at risk of developing endometriosis is with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 21. The method of any one of claims 18-20, wherein said identifying said subject as having   endometriosis or being at risk of developing endometriosis is with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 22. The method of any one of claims 18-21, wherein said subject is identified as having   endometriosis. 23. The method of claim 22, wherein said subject is asymptomatic for endometriosis. 24. The method of claim 22, wherein said subject is symptomatic for endometriosis. 25. The method of any one of claims 18-21, wherein said subject is identified as being at risk of developing endometriosis. 26. The method of any one of claims 1-25, further comprising administering a therapeutic to said subject. 27. The method of claim 26, wherein said therapeutic comprises hormonal therapy, an advanced reproductive technology therapy, a pain managing medication, or any combination thereof. 28. The method of claim 26, wherein said therapeutic comprises hormonal contraceptives,   gonadotropin-releasing hormone (Gn-RH) agonists, gonadotropin-releasing hormone (Gn- RH) antagonists, progestin, danazol, or any combination thereof. 29. The method of any one of claims 26-28, wherein said therapeutic comprises a pain medication. 30. The method of claim 29, wherein said pain medication comprises a nonsteroidal anti   inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof. 31. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 1. 32. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 2. 33. The method of any one of claims 1-26, wherein said one or more genetic variants are listed in Table 3. 34. The method of any one of claims 1-33, further comprising identifying said subject as having endometriosis-associated infertility or being at risk of developing endometriosis-associated infertility. 35. The method of claim 34, further comprising administering assisted reproductive technology therapy to said subject. 36. The method of claim 35, wherein said assisted reproductive technology therapy comprises in vitro fertilization, gamete intrafallopian transfer, or any combination thereof. 37. The method of claim 34, further comprising administering intrauterine insemination or   ovulation induction. 38. The method of any one of claims 1- 37, wherein said subject is a mammal. 39. The method of claim 38, wherein said mammal is a human. 40. The method of any one of claims 2-39, wherein said nanopore sequencing is performed with a biological nanopore, a solid state nanopore, or a hybrid nanopore. 41. The method of any one of claims 1-40, wherein said one or more genetic variants further comprise a mutation in SEPT 10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof. 42. The method of claim 41, wherein said one or more genetic variants comprise a mutation in SEPT10 and wherein said mutation comprises a missense mutation. 43. The method of claim 41, wherein said one or more genetic variants comprise a mutation in TNFRSF6B and wherein said mutation comprises a homozygous or hemizygous mutation. 44. The method of claim 41, wherein said one or more genetic variants comprise a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion. 45. The method of any one of claims 1-44, wherein the one or more variants are identified based on a predictive computer algorithm. 46. The method of claim 45, wherein said predictive computer algorithm is Polyphen 2, Sift, Mutation Accessor, Mutation Taster, FATHMM, LRT, or MetaLR. 47. The method of any one of claims 1-46, further comprising administering a hormonal therapy to said subject. 48. The method of claim 47, wherein the hormonal therapy comprises administration of   hormonal contraceptives, gonadotropin-releasing hormone (GnRH) agonists, gonadotropin releasing hormone (GnRH) antagonists, progestin, danazol, or any combination thereof. 49. The method of any one of claims 1-46, further comprising administering to the subject an assisted reproductive therapy. 50. The method of claim 49, wherein the assisted reproductive therapy comprises in vitro   fertilization, intrauterine insemination, ovulation induction, gamete intrafallopian transfer, or any combination thereof. 51. The method of any one of claims 1-46, further comprising administering to the subject a pain medication. 52. The method of claim 51, wherein the pain medication comprises a nonsteroidal anti   inflammatory drug (NSAID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof. 53. The method of any one of claims 1-46, further comprising administering a therapeutic to the subject. 54. The method of claim 53, wherein the therapeutic comprises a regenerative therapy, a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof. 55. The method of claim 53, wherein the therapeutic comprises a non-steroidal anti   inflammatory, a hormone treatment, a dietary supplement, a cannabis-derived therapeutic or any combination thereof. 56. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises an at least partially hemp-derived therapeutic, an at least partially cannabis-derived therapeutic, a cannabidiol (CBD) oil derived therapeutic, or any combination thereof. 57. The method of claim 53, wherein the therapeutic comprises the medical procedure, and   wherein the medical procedure comprises a laparoscopy, a laser ablation procedure, a hysterectomy or any combination thereof. 58. The method of claim 53, wherein the therapeutic comprises the regenerative therapy, and wherein the regenerative therapy comprises a stem cell, a cord blood cell, a Wharton’s jelly, an umbilical cord tissue, a tissue, or any combination thereof. 59. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises cannabis, cannabidiol oil, hemp, or any combination thereof. 60. The method of claim 53, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition is formulated in a unit dose. 61. The method of claim 53, wherein the therapeutic comprises hormonal therapy, an advanced reproductive therapy, a pain managing medication, or any combination thereof. 62. The method of claim 53, wherein the therapeutic comprises a hormonal contraceptive,   gonadotropin-releasing hormone (GnRH) agonist, gonadotropin-releasing hormone (GnRH) antagonist, progestin, danazol, or any combination thereof. 63. The method of any one of claims 1-62, wherein the subject is asymptomatic for   endometriosis. 64. A kit comprising: one or more probes for detecting one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof in a sample. 65. The kit of claim 64, further comprising a control sample. 66. The kit of claim 64, wherein the control sample comprises one or more genetic variants of Table 1, Table 2, Table 3, or any combination thereof. 67. The kit of any one of claims 64-66, wherein the one or more probes comprise a hybridization probe or amplification primer. 68. The kit of any one of claims 64-67, wherein the one or more probes is configured to associate with a solid support. 69. The kit of any one of claims 64-68, wherein the kit further comprises instructions for use and wherein the instructions for use comprise high stringent hybridization conditions. 70. The kit of any one of claims 64-69, wherein the one or more probes is configured to   hybridize to a target region of a nucleic acid of the sample, wherein the target region comprises one or more genetic variants. 71. A system comprising: (a) a computer processor configured to receive sequencing data   obtained from assaying a sample, wherein the computer processor is configured to identify a presence or an absence of one or more genetic variants of Table 1, Table 2, Table 3 or any combination thereof in the sample, and (b) a graphical user interface configured to display a report comprising the identification of the presence or the absence of the one or more genetic variants in the sample. 72. The system of claim 71, wherein the computer processor comprises a trained algorithm. 73. The system of claim 71 or 72, wherein the computer processor communicates a result. 74. The system of claim 73, wherein the result comprises an identification of the presence or the absence of one or more genetic variants in the sample. 75. A method comprising: (a) sequencing or genotyping a nucleic acid sample obtained from a subject having endometriosis, suspected of having endometriosis, or suspected of having a risk of developing endometriosis using a high throughput method; and (b) detecting a genetic variant in said nucleic acid sample, wherein said genetic variant comprises a mutation in SEPT 10, TNFRSF6B, UGT2B28, USP17L2 or any combination thereof. 76. The method of claim 75, wherein said genetic variant is a mutation in SEPT10 and wherein said mutation comprises a missense mutation. 77. The method of claim 75, wherein said genetic variant is a mutation in TNFRSF6B and   wherein said mutation comprises a homozygous or hemizygous mutation. 78. The method of claim 75, wherein said genetic variant is a mutation in UGT2B28 or USP17L2 and wherein said mutation comprises a hemizygous deletion. 79. The method of claim 75, wherein said high throughput method comprises nanopore   sequencing.
法律状态
PENDING
专利类型码
A1
国别省市代码
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