Genetic polymorphisms which are associated with autism spectrum Disorders

Abstract

A method is provided for screening subjects for genetic markers associated with autism. The method involves isolating a biological sample from a mammal and then testing for the presence of a mutated gene or a product thereof which is associated with autism. Also disclosed are isolated nucleic acids encoding HoxA1 and HoxB1, both of which have a polymorphism that is associated with autism spectrum disorders.

What is claimed:  
     
         1 . A method for screening subjects for genetic markers associated with autism, comprising: 
 isolating a biological sample from a mammal; and    testing the sample or genetic material isolated from the sample, for either a gene having a polymorphism or product thereof, which is a genetic marker for autism.    
     
     
         2 . The method according to  claim 1 , wherein the biological sample is selected from the group consisting of blood, saliva, amniotic fluid, and tissue.  
     
     
         3 . The method according to  claim 2 , wherein the biological sample is blood.  
     
     
         4 . The method according to  claim 1 , wherein the mammal is a human.  
     
     
         5 . The method according to  claim 4 , wherein the biological sample is isolated from developmentally disabled children.  
     
     
         6 . The method according to  claim 4 , wherein the biological sample is isolated from parents or relatives of developmentally disabled children.  
     
     
         7 . The method according to  claim 4 , wherein the biological sample is isolated from children and said method further comprises: 
 early behavior training for children having genetic markers associated with autism.    
     
     
         8 . The method according to  claim 1 , wherein the gene is selected from the group consisting of HoxA1, HoxB1, and HoxD1.  
     
     
         9 . The method according to  claim 8 , wherein the polymorphism is located in the homeobox.  
     
     
         10 . The method according to  claim 8 , wherein the gene is HoxA1.  
     
     
         11 . The method according to  claim 10 , wherein the gene has a single base substitution resulting in an amino acid substitution.  
     
     
         12 . The method according to  claim 11 , wherein the amino acid substitution is an arginine for a histidine.  
     
     
         13 . The method according to  claim 8 , wherein the gene is HoxB1.  
     
     
         14 . The method according to  claim 12 , wherein the gene has an insertion.  
     
     
         15 . The method according to  claim 14 , wherein the insertion is 5′ACAGCGCCC-3′.  
     
     
         16 . The method according to  claim 8 , wherein the mutated gene is HoxD1.  
     
     
         17 . The method according to  claim 1 , wherein the gene has a polymorphism selected from the group consisting of a single base substitution resulting in an amino acid substitution, a single base substitution resulting in a translational stop, an insertion, a deletion, and a rearrangement.  
     
     
         18 . The method according to  claim 1 , wherein the gene has a mutation in an exon.  
     
     
         19 . The method according to  claim 18 , wherein the polymorphism alters the sequence of the polypeptide encoded by the gene.  
     
     
         20 . The method according to  claim 1 , wherein the gene has a mutation in an intron.  
     
     
         21 . The method according to  claim 1 , wherein the gene has a mutation in a promotor or regulatory region.  
     
     
         22 . The method according to  claim 1 , wherein said testing is carried out by screening for a gene having a polymorphism.  
     
     
         23 . The method according to  claim 22 , wherein said screening for mutated nucleic acids is carried out by a method selected from the group consisting of direct sequencing of nucleic acids, single strand polymorphism assay, restriction fragment length polymorphism assay, ligase chain reaction, enzymatic cleavage and southern hybridization.  
     
     
         24 . The method according to  claim 23 , wherein said screening is carried out by direct sequencing of nucleic acids.  
     
     
         25 . The method according to  claim 23 , wherein said screening is carried out by single strand polymorphism assay.  
     
     
         26 . The method according to  claim 23 , wherein said screening is carried out by restriction fragment length polymorphism assay.  
     
     
         27 . The method according to  claim 23 , wherein said screening is carried out by ligase chain reaction.  
     
     
         28 . The method according to  claim 23 , wherein said screening is carried out by enzymatic cleavage.  
     
     
         29 . The method according to  claim 23 , wherein said screening is carried out by southern hybridization.  
     
     
         30 . The method according to  claim 23 , wherein the nucleic acid is a deoxyribonucleic acid.  
     
     
         31 . The method according to  claim 23 , wherein the nucleic acid is a messenger ribonucleic acid.  
     
     
         32 . The method according to  claim 1 , wherein said testing is carried out by screening for polypeptides resulting from said gene having a polymorphism.  
     
     
         33 . The method according to  claim 32 , wherein said screening for the polypeptide resulting from said gene having a polymorphism is carried out by a method selected from the group consisting of probing with antibodies specific to said polypeptide, measurement of the concentration of said polypeptide, and measuring the size of said polypeptide.  
     
     
         34 . The method according to  claim 33 , wherein said screening is carried out by probing with antibodies specific to said polypeptide.  
     
     
         35 . The method according to  claim 33 , wherein said screening is carried out by measuring the size of the polypeptides.  
     
     
         36 . An isolated nucleic acid molecule comprising a single base substitution at nucleotide 218 in SEQ. ID. No. 1, or a fragment having at least 15 nucleotides encompassing said single base substitution.  
     
     
         37 . An isolated polypeptide encoded by the nucleic acid of  claim 36 .  
     
     
         38 . An antibody which binds to the isolated polypeptide according to  claim 37  and which does not bind to the wild-type HoxA1 protein of SEQ. ID. No. 2.  
     
     
         39 . An isolated nucleic acid molecule comprising an insertion between positions nucleotides 88 and 89 in SEQ. ID. No. 5, or a fragment having at least 15 nucleotides encompassing said insertion.  
     
     
         40 . The isolated nucleic acid molecule according to  claim 39 , wherein the insertion is 5′-ACAGCGCCC-3′.  
     
     
         41 . An isolated polypeptide encoded by the nucleic acid of  claim 39 .  
     
     
         42 . An antibody which binds to the isolated polypeptide according to claim  41  and which does not bind to the wild-type HoxB1 protein of SEQ. ID. No. 6.