Peripheral gene expression biomarkers for autism

Abstract

The disclosed invention comprises methods and materials for screening cells for genetic profiles associated with autism spectrum disorders. The methods typically involve isolating a cell from an individual and then observing the expression profile of one or more genes in the cell, wherein certain expression patterns of the genes observed are associated with autism spectrum disorders.

1 . A kit comprising:
 a container;   a primer composition contained within said container, wherein the primer composition includes a polymerase chain reaction (PCR) primer effective in the quantitative real time analysis of the mRNA expression levels of one or more genes selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16; and   a pharmaceutically-acceptable buffer composition.   
     
     
         2 . The kit of  claim 1 , wherein the kit comprises a plurality of chain reaction (PCR) primers effective in the quantitative real time analysis of the mRNA expression levels of different genes selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16. 
     
     
         3 . The kit of  claim 1 , further comprising a computer readable a memory storage element adapted to process and store data from one or more expression profiles. 
     
     
         4 . The kit of  claim 3 , wherein the memory storage element organizes expression profile data into a format adapted for electronic comparisons with a library of expression profile data. 
     
     
         5 . The kit of  claim 2 , wherein the plurality of chain reaction (PCR) primers are used to observe expression levels of at least two, three, or four of the different genes. 
     
     
         6 . The kit of  claim 5 , wherein the at least two, three, or four of the different genes is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16. 
     
     
         7 . The kit of  claim 6 , wherein at least one of the at least two, three, or four of the different genes is selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16. 
     
     
         8 . The kit of  claim 1 , wherein the primer composition is used to observe expression levels of at least one of the genes selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16. 
     
     
         9 . The kit of  claim 1  wherein at least two of the at least two, three, or four genes is selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16. 
     
     
         10 . The kit of  claim 1 , wherein the primer is adapted to bind to mRNA expressed by a human leukocyte. 
     
     
         11 . A method of identifying a test mammalian cell having a gene expression profile observed in individuals diagnosed with autism comprising:
 observing an expression profile of at least one gene selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16 in the test mammalian cell; wherein:   an expression profile of a gene in the group that is at least two standard deviations from a mean expression profile of the gene in a control mammalian cell obtained from an individual not affected with autism identifies the test mammalian cell as having a gene expression profile observed in individuals diagnosed with autism; and   the test mammalian cell is obtained from an individual where at least one evaluation is performed from a diagnostic procedure for autism.   
     
     
         12 . The method of  claim 11 , wherein the at least one evaluation is selected from the group consisting of: (a) a Autism Diagnostic Interview (ADI-R), (b) an Autism Diagnostic Observation Schedule (ADOS), or (c) an IQ surrogate test based on Raven's Progressive Matrices. 
     
     
         13 . The method of  claim 11 , wherein the at least one evaluation includes observations of restricted repetitive behaviors or speech delay. 
     
     
         14 . The method of  claim 11 , wherein the at least one evaluation is performed prior to observing the expression profile of the at least one gene. 
     
     
         15 . The method of  claim 11 , wherein the method is used in a diagnosis of autism. 
     
     
         16 . The method of  claim 11 , wherein the method is performed on a plurality of individuals. 
     
     
         17 . The method of  claim 16 , wherein expression profiles obtained from the plurality of individuals are segregated based upon a degree of standard deviation from a mean expression profile of the gene in a control mammalian cell obtained from an individual not affected with autism. 
     
     
         18 . The method of  claim 11 , wherein the expression profiles of at least two, three, or four genes is observed. 
     
     
         19 . The method of  claim 11 , wherein the test mammalian cell or the control mammalian cell is a leukocyte obtained from the peripheral blood. 
     
     
         20 . The method of  claim 11 , wherein the test mammalian cell and the control mammalian cell are obtained from individuals who are related as siblings or as a parent and a child.