Novel apolipoprotein gene involved in lipid metabolism
AssigneeThe Regents of the University of California
InventorsEdward Rubin, Len A. Pennacchio
Life of this patent
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Abstract
Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.
Claims33
A transgenic non-human animal comprising a genome having the human gene APOAV, at least 70% homologous to a DNA sequence selected from SEQ ID NO:
- 3 or SEQ ID NO:
- 4 or SEQ ID NO:
- 5, wherein triglyceride levels in said animal are reduced.
A non-human animal comprising a genome having a functionally disrupted apoA5 gene, wherein the triglyceride levels in said animal are increased.
Cloned and isolated mouse genomic DNA comprising SEQ ID NO:
- 6 for use in non-human animal studies.
A synthetic polynucleotide having a sequence encompassing one or more of SNPs 1-3, 5 or 6 as described in SEQ ID NO:
- 3 for use in detecting the presence of a wild-type or a rare allele of said SNPs.
A method for determining the genetic status of an individual, comprising:
- a. detecting the presence of one of more of SNPs 1-3, 5 or 6 in DNA or RNA of the individual;
- and
- b. determining whether the SNP is the common nucleotide or the uncommon nucleotide, whereby
- c. the presence of one or more uncommon SNP nucleotides indicates a predisposition for elevated triglyceride levels in the individual.
A method for determining predisposition towards elevated triglyceride levels of an individual, comprising determining the level of APOAV gene expression, wherein elevated APOAV gene expression is associated with decreased risk of elevated triglycerides and lowered APOAV gene expression is associated with increased risk of elevated triglycerides.
An isolated APOAV polypeptide having the amino acid sequence of SEQ ID NO:
- 7.
An isolated polynucleotide having at least 70% homology to the cDNA APOAV sequence selected from the group consisting of SEQ ID NO:
- 1 and SEQ ID NO:
- 2.
An antibody to a polypeptide of SEQ ID NO:
- 7.
A method for genotyping an individual comprising the use of at least one SNP selected from the following single nucleotide polymorphisms described in SEQ ID NO:
- 3:
- Position Number 11674 SNP 3 (T>C),
- Position Number 12802 SNP 6(A>G), located in the 5′ untranslated region of the APOAV mRNA and cDNA,
- Position Number 12974 SNP 5 (C>G), causing an amino acid change in the APOAV gene product,
- Position Number 13555 SNP 2 (G>A), and
- Position Number 14695 SNP 1 (T>C),
- wherein the common nucleotide is given to the left of the arrow and the uncommon nucleotide is given to the right of the arrow.
A method for identifying a drug which lowers plasma lipid levels, comprising the steps of:
- (a) contacting a drug candidate with a cell expressing APOAV;
- (b) measuring the effect of the drug candidate on the expression of APOAV in the cell by the comparison of APOAV expression both with and without the drug candidate;
- (c) selecting as a drug a drug candidate which causes increased APOAV expression.
A method for identifying a drug which lowers plasma lipid levels, comprising the steps of:
- (a) contacting a drug candidate with a cell expressing a rare allele of APOAV;
- (b) measuring the effect of the drug candidate on the expression of APOAV in the cell by the comparison of APOAV expression both with and without the drug candidate;
- (c) selecting as a drug a drug candidate which causes decreased APOAV expression.
Dependencies are inferred from the claim text.