Polynucleotides encoding for polymorphic isoforms of the pthrp protein, the encoded proteins and their therapeutic applications thereof
OwnerTommaso A Dragani, Giacomo Manentiinventors
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Abstract
Described herein is the identification of two polymorphic isoforms of the gene encoding the PTHrP protein, of the allelic proteins, of a first polynucleotide comprising the polymorphic domain corresponding to SEQ ID NO: 2 and comprising a first polymorphic position, of a second polynucleotide comprising a second polymorphic domain and corresponding to SEQ ID NO: 7 which encode for two variants of the PTHrP protein; also described is the use of these genes, alleles or polynucleotides to determine the risk of tumor in animals and humans and genetically modified cells and non-human animals.
Claims61
Polynucleotide encoding a polymorphic PTHrP (ParaThyroid Hormone related Protein) or a fragment thereof, said protein or fragment comprising the polymorphic domain TSXPSLE corresponding to SEQ ID NO:
- 2.
Polynucleotide comprising the nucleotide sequence corresponding to SEQ ID NO:
- 3.
Polynucleotide encoding a polymorphic PTHrP or a fragment thereof, said protein or fragment comprising the polymorphic domain ASSGLLDYP, (SEQ ID NO:
- 7).
Polynucleotide comprising the nucleotide sequence corresponding to SEQ ID NO:
- 8.
Polynucleotide encoding a polymorphic PTHrP or a fragment thereof, comprising the polymorphic domain TSXPSLE of SEQ ID NO:
- 2 and the polymorphic domain ASSGLLDYP of SEQ ID NO:
- 7.
Allelic variant of the Pthlh gene encoding a polymorphic PTHrP or a fragment thereof comprising the domain of SEQ ID NO:
- 2
Allelic variant comprising the polymorphic base corresponding to position 496 of SEQ ID NO:
- 3.
Allelic variant corresponding to SEQ ID NO:
- 3.
Allelic variant of the Pthlh gene encoding for polymorphic a PTHrP or a fragment thereof comprising the domain corresponding to SEQ ID NO:
- 7
Allelic variant comprising the polymorphic bases corresponding to positions 454, 471, 472 of SEQ ID NO:
- 8.
Allelic variant with sequence SEQ ID NO:
- 8.
Allelic variant comprising the allelic variant according to claim 17 and according to claim 23 21.
Polymorphic PTHrP or a fragment thereof comprising the polymorphic domain of SEQ ID NO:
- 2.
Protein or fragment comprising at least one of the sequences chosen in the group consisting of:
- SEQ ID NO:
- 2, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 10.
Polymorphic PTHrP or a fragment thereof comprising the polymorphic domain of SEQ ID NO:
- 2 and the polymorphic domain of SEQ ID NO:
- 7
Method for identifying the polymorphism of the Pthlh gene encoding the polymorphic PTHrP or a fragment thereof comprising the domain of SEQ ID NO:
- 2 and/or the domain of SEQ ID NO:
- 7, in an animal or human subject, comprising the steps of:
- obtaining a biological sample from the subject
- analyze the sample to identify said polymorphic Pthlh allelic variant.
Kit for the identifying and/or determining the polymorphism of a polynucleotide or nucleic acid sequence or of the gene encoding the PTHrP protein or a fragment thereof comprising the polymorphic domain corresponding to SEQ ID NO:
- 2 and/or the domain corresponding to SEQ ID NO:
- 7, comprising:
- (a) a first container comprising the primers for amplification of regions of the polynucleotide encoding a polymorphic PTHrP protein or a fragment thereof comprising at least one of said polymorphic domains;
- and
- (b) a second container comprising the oligonucleotidic primers to determine at least one of said polymorphisms.
Antisense oligonucleotide for blocking and inactivating specifically the polymorphic Pthlh gene or the DNA sequence encoding for a peptide comprising the polymorphic domain of SEQ ID NO:
- 2 and/or SEQ ID NO:
- 7, with the provision that said antisense olygonucleotide has not the following sequence:
- 5′TGAACCAGCGACCGCAAGCM.
Antibodies or peptide fragments for blocking and inactivating specifically the polymorphic PTHrP or a fragment thereof comprising the polymorphic domain SEQ ID NO:
- 2 and/or of SEQ ID NO:
- 7.
Dependencies are inferred from the claim text.