Compositions, reagents and kits for and methods of diagnosing, monitoring and treating obesity and/or diabetes

A method for detecting the presence of at least one variant nucleic acid sequence of obesity and/or diabetes related genes in a biological sample comprising the steps of:

• (a) hybridizing to nucleic acid material of the biological sample an isolated nucleic acid sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, or a complement thereof;
• and
• (b) detecting a hybridization complex produced by step (a);
• wherein the presence of the hybridization complex correlates with the presence of at least one variant nucleic acid sequence in the biological sample.

A method for determining the level of variant nucleic acid sequences in a biological sample comprising the steps of:

• (a) hybridizing to nucleic acid material of the biological sample an isolated nucleic acid sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,
• SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, or a complement thereof;
• (b) determining the amount of hybridization complexes produced by step (a);
• and
• (c) normalizing the amount of hybridization complexes to provide a level of variant nucleic acid sequences in the biological sample.

A method for determining the ratio between the level of a nucleic acid sequence of an obesity and/or diabetes related gene variant in a first biological sample and a variant produced by alternative splicing in a second biological sample comprising the steps of:

• (a) determining the level of a first nucleic acid sequence of an obesity and/or diabetes related gene variant in a first biological sample;
• (b) determining the level of a second nucleic acid sequence of an alternative splicing form of the variant in a second biological sample;
• and
• (c) comparing the levels obtained in step (a) and step (b) to give a ratio.

A method for the identification of compounds capable of affecting the binding affinity of obesity and/or diabetes related proteins to the receptors of said proteins comprising the steps of:

• (a) providing an amino acid sequence selected from SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:41, and SEQ ID NO:42;
• (b) contacting a candidate compound with the amino acid sequence in the presence of at least one receptor of an obesity and/or diabetes related gene;
• (c) determining the effect of the candidate compound on the binding of the amino acid sequence to the at least one receptor;
• and
• (d) selecting a compound capable of affecting the binding affinity of obesity and/or diabetes related proteins to the receptors of said proteins.

A method for determining the ratio between the level of an obesity and/or diabetes related protein variant in a first biological sample and a variant produced by alternative splicing in a second biological sample comprising the steps of:

• (a) determining the level of a first amino acid sequence of an obesity and/or diabetes related gene variant in a first biological sample;
• (b) determining the level of a second amino acid sequence of an alternative splicing form of the variant in a second biological sample;
• and
• (c) comparing the levels obtained in step (a) and step (b) to give a ratio.