Allelic Form of the HMGA2 Gene Predisposing Women to the Formation of Leiomyomas

Abstract

The present invention is directed to diagnostic assays that can be used to determine if a woman carries an allelic form of the HMGA2 gene that predisposes her to the formation of fibroid tumors. The invention also encompasses vectors containing this allele, cells transformed with these vectors and transgenic animals that carry at least one copy of the allele.

1 - 21 . (canceled) 
     
     
         22 . A diagnostic kit comprising one or more components needed to conduct an assay to determine if a woman carries an HMGA2 allele that predisposes her to the formation of uterine fibroids. 
     
     
         23 . The diagnostic kit of  claim 22 , comprising an oligonucleotide that can be used to determine if a woman carries an HMGA2 allele that predisposes her to the formation of uterine fibroids. 
     
     
         25 . The diagnostic kit of  claim 22 , wherein said assay comprises:
 a) determining if the genome of said woman includes an allelic form of an HMGA2 gene sequence encoding the protein of either SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3, wherein said HMGA2 gene is characterized by a repeat sequence (TC) n  where n=27, located in the 5′ untranslated region of said gene; and   b) concluding that said woman is predisposed to developing uterine fibroids if said allelic form is present.   
     
     
         26 . The diagnostic kit of  claim 25 , wherein said repeat sequence in said assay is located 400-800 nucleotides 5′ to the ATG translation start codon of said HMGA2 gene as shown in SEQ ID NOs:4-7. 
     
     
         27 . The diagnostic kit of  claim 26 , wherein said repeat sequence is found 500-700 nucleotides 5′ to the ATG translation start of said HMGA2 gene as shown in SEQ ID NOs:4-7. 
     
     
         28 . The diagnostic kit of  claim 25 , wherein the determination of step a) in said assay includes an amplification of the region of said HMGA2 gene comprising said repeat sequence by PCR. 
     
     
         29 . The diagnostic kit of  claim 28 , wherein said region comprises at least 54 sequential nucleotides located in the region 400-800 nucleotides 5′ to the ATG start codon of said HMGA2 gene. 
     
     
         30 . The diagnostic kit of  claim 29 , wherein the PCR amplification produces a product 54-400 nucleotides in length. 
     
     
         31 . The diagnostic kit of  claim 28 , wherein said assay further comprises either:
 a) sequencing the amplification product produced;   b) analyzing the size of the amplification product; or   c) analyzing the amplification product by hybridization under stringent conditions.   
     
     
         32 . The diagnostic kit of  claim 31 , wherein amplification by PCR is performed using primers comprising the sequences of SEQ ID NO:11 and SEQ ID NO:12. 
     
     
         33 . The diagnostic kit of  claim 31 , wherein amplification by PCR is performed using, in part, a primer consisting of the sequence of SEQ ID NO:11. 
     
     
         34 . The diagnostic kit of  claim 31 , wherein amplification by PCR is performed using, in part, a primer consisting of the sequence of SEQ ID NO:12. 
     
     
         35 . A diagnostic kit comprising one or more oligonucleotide primers that can be used to amplify an HMGA2 gene region by PCR, wherein said gene region includes the TC rich region from the 5′ untranslated region of said HMGA2 gene. 
     
     
         36 . The diagnostic kit of  claim 35 , wherein said gene region includes at least a portion of the 5′ UTR sequence located between 400 and 800 nucleotides 5′ to the HMGA2 ATG initiation site. 
     
     
         37 . The diagnostic kit of  claim 35 , wherein said kit further comprises instructions for amplifying the 5′ untranslated region of the HMGA2 gene of a woman to determine if it includes a (TC) 27  repeat sequence. 
     
     
         38 . The diagnostic kit of  claim 35 , wherein said one or more primers include an oligonucleotide comprising the sequence of either SEQ ID NO:11 or SEQ ID NO:12. 
     
     
         39 . The diagnostic kit of  claim 35 , comprising a primer consisting of the sequence of SEQ ID NO:11. 
     
     
         40 . The diagnostic kit of  claim 35 , comprising a primer consisting of the sequence of SEQ ID NO:12. 
     
     
         41 . The diagnostic kit of  claim 35 , comprising:
 a) a primer consisting of the sequence of SEQ ID NO:11;   b) a primer consisting of the sequence of SEQ ID NO:12;   c) instructions for amplifying the 5′ untranslated region of the HMGA2 gene of a woman to determine if it includes a (TC) 27  repeat sequence.