Biomarkers for autism spectrum disorders

Abstract

Methods of determining the risk of ASD in an individual are provided which comprise identifying the presence of one or more genomic mutations in one or more of the genes, PTCHD1, SHANK3, NFIA, DPP6, DPP10, DYPD, GPR98, PQBP1, ZNF41 and FTSJ1.

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         17 . A method of determining the risk of ASD in an individual comprising:
 probing a nucleic acid-containing sample obtained from the individual for a genomic sequence mutation in at least one gene selected from the group consisting of PTCHD1, SHANK3, NFIA, DPP6, DYPD, DPP10, GPR98, PQBP1, ZNF41 and FTSJ1, wherein identification of a mutation that modulates the expression of at least one of said genes is indicative of a risk of ASD.   
     
     
         18 . A method as defined in  claim 17 , wherein the genomic sequence variation is in the PTCHD1 gene. 
     
     
         19 . A method as defined in  claim 17 , wherein the genomic sequence mutation is a deletion of at least a portion of exon 1 of PTCHD1. 
     
     
         20 . A method as defined in  claim 17 , wherein the genomic sequence mutation is an intronic gain in DPP10. 
     
     
         21 . A method as defined in  claim 17 , wherein the genomic sequence mutation is an exonic loss in DPP10. 
     
     
         22 . A method as defined in  claim 17 , wherein the genomic sequence mutation is an exonic loss encompassing at least a portion of exons 2 and 3 in DPP6. 
     
     
         23 . A method as defined in  claim 17 , wherein the genomic sequence mutation is a gain in DPP6 selected from at least one of the group consisting of the entire DPP6 gene, a 270 kb exonic gain in exon 1 and a 16 kb intronic gain. 
     
     
         24 . A method as defined in  claim 17 , wherein the genomic sequence mutation is a loss in the SHANK3 gene. 
     
     
         25 . A method as defined in  claim 17 , wherein the genomic sequence mutation is a loss of the DYPD gene. 
     
     
         26 . A method as defined in  claim 17 , wherein the genomic sequence mutation is at least one missense mutation in PTCHD1 resulting in at least one amino acid substitution in the encoded protein selected from the group consisting of L73F, I173V, V195I, ML336-337II and E479G. 
     
     
         27 . A method as defined in  claim 17 , wherein the genomic sequence mutation is selected from the group consisting of a deletion of at least a portion of exon 1 of PTCHD1; an intronic gain in DPP10; an exonic loss in DPP10; an exonic loss encompassing at least a portion of exons 2 and 3 in DPP6; a gain in DPP6 selected from at least one of the group consisting of the entire DPP6 gene, a 270 kb exonic gain in exon 1 and a 16 kb intronic gain; a loss in the SHANK3 gene; a loss of the DYPD gene; and at least one missense mutation in PTCHD1 resulting in at least one amino acid substitution in the encoded protein selected from the group consisting of L73F, I173V, V195I, ML336-337II and E479G. 
     
     
         28 . A method of determining the risk of ASD in an individual comprising:
 screening a biological sample from the individual for abnormal levels of at least one gene product expressed by a gene selected from the group consisting of PTCHD1, SHANK3, NFIA, DPP6, DPP10, DYPD, GPR98, PQBP1, ZNF41 and FTSJ1, wherein a determination that at least one of said gene products is expressed at a level that varies from the expression level in a healthy non-ASD individual is indicative of a risk of ASD.   
     
     
         29 . The method as defined in  claim 28 , wherein the biological sample is screened for abnormal levels of the PTCHD1 gene product. 
     
     
         30 . A method of determining the risk of ASD in an individual comprising:
 screening a nucleic acid-containing sample from the individual for at least one genomic sequence variation that modulates the expression of PTCHD1, wherein identification of at least one of said genomic sequence variations is indicative of a risk of ASD in the individual.   
     
     
         31 . A method as defined in  claim 30 , wherein the genomic sequence variation is in the PTCHD1 gene. 
     
     
         32 . A method as defined in  claim 30 , wherein the genomic sequence variation is a deletion of at least a portion of exon 1 of PTCHD1. 
     
     
         33 . A method as defined in  claim 30 , wherein the genomic sequence variation is at least one missense mutation in PTCHD1 resulting in at least one amino acid substitution in the encoded protein selected from the group consisting of L73F, I173V, V195I, ML336-337II and E479G.