Methods and compositions for diagnosing, prognosing, and treating endometriosis

Abstract

This document provides methods and materials related to genetic variations associated with endometriosis. For example, this document provides methods for using such genetic variations to assess risk of, or susceptibility of developing or diagnosing endometriosis.

1 - 19 . (canceled) 
     
     
         20 . A method comprising:
 (a) (i) hybridizing a nucleic acid probe to a polynucleic acid, wherein the polynucleic acid is from a sample from a human female subject with endometriosis, or
 (ii) synthesizing a nucleic acid product from a polynucleic acid, wherein the polynucleic acid is from a sample from a human female subject with endometriosis; and 
   (b) detecting in the polynucleic acid at least one genetic variation comprising a copy number variation (CNV) from a panel of low frequency genetic variations;   wherein detecting comprises detecting by PCR, sequencing, nucleic acid hybridization, microarray analysis or northern blot or a combination thereof,   wherein the panel of low frequency genetic variations comprises at least one low frequency genetic variation for each of a plurality of genetic loci, and   wherein the at least one low frequency genetic variation occurs at a frequency of 0.1% or less in a population of female subjects without a diagnosis of endometriosis.   
     
     
         21 . The method of  claim 20 , wherein the CNV introduces a breakpoint in a gene. 
     
     
         22 . The method of  claim 20 , wherein detecting comprises detecting at least two genetic variations. 
     
     
         23 . The method of  claim 20 , wherein the CNV occurs in an exon of a gene. 
     
     
         24 . The method of  claim 23 , wherein the gene is selected from the group consisting of: HMGB3, IMPK, ACCS, PTK2, MUC4, MAGEA11, MSN, MYADML, CRHR2, PLA2G4C, NCOA1, and BNC2. 
     
     
         25 . The method of  claim 24 , wherein the CNV comprises a sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO:31, SEQ ID NO: 33 and SEQ ID NO: 35. 
     
     
         26 . The method of  claim 23 , wherein the CNV disrupts a function of at least two genes. 
     
     
         27 . The method of  claim 26 , wherein the CNV comprises a sequence selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 34. 
     
     
         28 . The method of  claim 20 , wherein the CNV occurs in an intron of a gene or an intergenic region. 
     
     
         29 . The method of  claim 28 , wherein the CNV comprises a sequence selected from the group consisting of: SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 21 and SEQ ID NO: 30. 
     
     
         30 . The method of  claim 20 , wherein the polynucleic acid comprises blood, saliva, urine, serum, tears, skin, tissue or hair from the human female subject. 
     
     
         31 . The method of  claim 20 , wherein detecting comprises detecting by multiplex ligation-dependent probe amplification (MLPA), molecular beacon, array Comparative Genomic Hybridization, Invader assay, ligase chain reaction (LCR), fluorescence in situ hybridization, or any combination thereof. 
     
     
         32 . The method of  claim 20 , wherein detecting comprises detecting by whole genome sequencing or whole exome sequencing. 
     
     
         33 . The method of  claim 20 , wherein the method further comprises administering a pharmaceutical composition for treating endometriosis to the subject. 
     
     
         34 . The method of  claim 20 , wherein the human female subject is asymptomatic or is infertile. 
     
     
         35 . The method of  claim 24 , wherein the CNV causes loss of function of a PLA2G4C gene. 
     
     
         36 . The method of  claim 23 , wherein the gene is selected from group consisting of LEPR, CNNM2, MKRN1 and SLC37A3. 
     
     
         37 . The method of  claim 32 , wherein the detecting further comprises an in-silico analysis. 
     
     
         38 . The method of  claim 20 , wherein the detecting comprises detecting a first genetic variation, wherein the first genetic variation is the CNV of the PLA2G4C gene, wherein the first genetic variation and a second genetic variation are in a panel comprising two or more genetic variations.