Method of diagnosis of type 2 diabetes and early onset thereof
OwnerPhilippe Froguel, Christian Dina +2inventors
InventorsPhilippe Froguel, Christian Dina, Bernadette Neve, Danielle Melloul
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Abstract
The invention pertains to the field of human genetics and relates to new methods of diagnosis and therapy of type 2 diabetes (T2D), early onset type 2 diabetes and Maturity-Onset Diabetes of the Young (MODY) in a human subject, based on the identification of the A185G variation located at exon 2 of the tieg2 gene as well as the G-1534C, 54a, 304a, +659 C>T (Thr220Met) and +1039 G>T (A1a347Ser) variations.
Claims17
A method for diagnosing a predisposition for type 2 diabetes, early onset type 2 diabetes and Maturity-Onset Diabetes of the Young (MODY) in a human subject which comprises determining whether there is a germline variation in the sequence of the tieg2 gene, said variation being indicative of a predisposition to type 2 diabetes, wherein said variation is selected from A185G numbered with regards to the start codon of the tieg2 gene, the coding sequence of which is represented by SEQ ID No 1, G-1534C as shown in SEQ ID No 4, 54a or 304a as shown in FIGS. 4A and 4B, and +659 C>T (Thr220Met) and +1039 G>T (A1a347Ser) of which the sequences are represented in SEQ ID No40 and 41 as shown in FIGS. 7 and 8 respectively.
A method for identifying variations in the sequence of the tieg2 gene, comprising determining whether there is a mismatch between molecules (1) a region tieg2 gene genomic DNA isolated from said sample, and (2) a nucleic acid probe complementary to human wild-type region of the tieg2 gene DNA, when molecules (1) and (2) are hybridized to each other to form a duplex, and said mismatch being due to the presence of at least one variation in the sequence of the tieg2 gene genomic DNA isolated from said sample.
A method for identifying variations in exon 2 of the tieg2 gene comprising determining whether there is a mismatch between molecules (1) exon 2 of the tieg2 gene genomic DNA isolated from said sample, and (2) a nucleic acid probe complementary to human wild-type exon 2 region of the tieg2 gene DNA as represented by SEQ ID No 2, when molecules (1) and (2) are hybridized to each other to form a duplex, and said mismatch being due to the presence of at least one variation in the sequence of the tieg2 gene genomic DNA isolated from said sample.
A method for identifying variations in the tieg2 gene comprising determining whether there is a mismatch between molecules (1) the tieg2 gene genomic DNA isolated from said sample, and (2) a nucleic acid probe complementary to human tieg2 gene DNA covering the +659 C>T (Thr220Met) and +1039 G>T (A1a347Ser) variants sequences such as a probe deriving from the sequence gacacacacctcaXggacagt-(SEQ ID No 42) wherein X is C or T and a probe deriving from the sequence ttggtcctgccccagggaYccctccctccg-(SEQ ID No 43) wherein Y is G or T.
A probes or a primer selected from SEQ ID No5 to SEQ ID No36 and primers deriving from SEQ ID No42 and 43.
A variant of TIEG2 selected from the GIn62Arg protein variant of TlEG2 of SEQ ID no 3, the Thr220Met protein variant, the A1a347Ser protein variant, and a variant displaying at least 2 of the following variations:
- GIn62Arg,
- Thr220Met,
- A1a347Ser.
A method for screening compounds capable of preventing and/or treating type 2 diabetes which comprises:
- combining (i) a candidate compound and (ii) a TIEG2 polypeptide and determining the amount of binding of the TIEG2 polypeptide to said compound.
A vector suitable for gene therapy, comprising the coding sequence for the wild-type TIEG2 operatively linked to a promoter allowing the expression of said coding sequence in human cells.
A transgenic non-human mammal whose genome comprises a disruption of the endogenous tieg2 gene, as an animal model for type 2 diabetes, early onset type 2 diabetes and Maturity-Onset Diabetes of the Young (MODY).
Dependencies are inferred from the claim text.