DIAGNOSIS AND PREDICTION OF AUSTISM SPECTRAL DISORDER
Methods and compositions for the detection of single nucleotide polymorphisms (SNP) to determine whether the subject has autism spectrum disorder (ASD), is likely to develop ASD, or to classify a subject as having a particular ASD subtype. The presence and/or absence of the one or more SNPs is compared to the presence and/or absence of the SNPs in at least one sample training set(s), where the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the SNP data obtained from the sample and the SNP data from the at least one training set.
1 . A method for diagnosing a sample from a human subject as ASD-positive or ASD negative, comprising
detecting the presence of single nucleotide polymorphism (SNP) classifier biomarkers in Table 1, Table 2, Table 3, Table 6 or Table 7 at the nucleic acid level by performing a hybridization assay comprising polymerase chain reaction (PCR) with primers specific to the classifier biomarkers to determine a SNP profile;
comparing the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 to the presence and/or absence of the SNP classifier biomarkers in at least one sample training set(s), wherein the at least one sample training set(s) comprise (i) data of the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 from an ASD positive sample or (ii) data of the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 from an ASD-negative sample; and
diagnosing the sample as ASD positive or ASD negative based on the SNP profile.
2 . A method for classifying a sample from a human subject as a particular ASD subtype, comprising,
detecting the presence of SNP classifier biomarkers in Table 1, Table 2, Table 3, Table 6 or Table 7 at the nucleic acid level by performing a hybridization assay comprising polymerase chain reaction (PCR) with primers specific to the classifier biomarkers to determine a SNP profile;
comparing the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 to the presence and/or absence of the SNP classifier biomarkers in at least one sample training set(s), wherein the at least one sample training set(s) comprise (i) data of the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 from a first ASD subtype positive sample or (ii) data of the presence and/or absence of the SNP classifier biomarkers of Table 1, Table 2, Table 3, Table 6 or Table 7 from a second ASD subtype-positive sample; and
diagnosing the sample as a particular ASD subtype based on the SNP profile.
3 . The method of claim 1 , wherein the SNP classifier biomarkers comprise twelve or more SNP classifier biomarkers, thirteen or more SNP classifier biomarkers, fourteen or more SNP classifier biomarkers, fifteen or more SNP classifier biomarkers, twenty or more SNP classifier biomarkers, twenty-five or more SNP classifier biomarkers, or thirty or more SNP classifier biomarkers.
4 . The method of claim 1 , wherein the hybridization assay is a microarray assay.
5 . The method of claim 1 , wherein the hybridization assay is a sequencing assay.
6 . The method of claim 1 , wherein the sample is from the human subject is a buccal sample.
7 . The method of claim 1 , further comprising applying a statistical algorithm which comprises determining a correlation between the SNP classifier biomarker data obtained from the sample and the SNP classifier biomarker data from the at least one training set.
8 . The method of claim 2 , wherein the first ASD subtype and second ASD subtype are selected from the group consisting of Autistic disorder (classic autism), Asperger's disorder (Asperger syndrome), Pervasive developmental disorder not otherwise specified (PDD-NOS), and Childhood disintegrative disorder (CDD), wherein the first ASD subtype and second ASD subtype are different.
9 . The method of claim 1 , wherein the one or more SNP classifier biomarkers comprise SNPs in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes.
10 . The method of claim 9 , wherein the RAB11FIP5 SNP is located at chr2:73302656 (hg19), the ABP1 SNP is located at chr7:150554592 (hg19) and the JMJD7-PLA2G4B SNP is located at chr15:42133295 (hg19).
11 . The method of claim 5 , wherein the sequencing assay is a high throughput sequencing assay.
12 .- 17 . (canceled)
18 . The method of claim 1 , wherein the primers comprise SEQ ID NOs:1-78.
19 . The method of claim 2 , wherein the primers comprise SEQ ID NOs:1-78.
20 . A method for detecting the presence of single nucleotide polymorphism (SNP) classifier biomarkers in Table 1, Table 2, Table 3, Table 6 or Table 7 at the nucleic acid level by performing a hybridization assay comprising polymerase chain reaction (PCR) with primers specific to the classifier biomarkers, wherein the primers comprise SEQ ID NOs:1-78.
21 . An oligonucleotide set comprising SEQ ID NOs:1-78.
22 . An in vitro diagnostic test for detecting the presence of single nucleotide polymorphism (SNP) classifier biomarkers in Table 1, Table 2, Table 3, Table 6 or Table 7, wherein the test comprises primers specific to the classifier biomarkers.
23 . The in vitro diagnostic test of claim 22 , wherein the primers comprise SEQ ID NOs:1-78.
24 . The in vitro diagnostic test of claim 22 , further comprising one or more devices, tools, or equipment configured to collect a genetic sample from an individual.
25 . The in vitro diagnostic test of claim 22 , further comprising a reagent or solution for collecting, stabilizing, storing, and processing a genetic sample.
26 . The in vitro diagnostic test of claim 22 , further comprising a microarray apparatus.