Identification of Gene Associated with Reading Disability and Uses Therefor

Abstract

The present invention relates to identification of a human gene, DCDC2 (MIM: 605755), associated with susceptibility for developing reading disability (RD), which is useful in identifying or aiding in identifying individuals at risk for developing RD, as well as for diagnosing or aiding in the diagnosis of RD.

1 . An isolated polynucleotide for the detection of a human DCDC2 gene associated with reading disability (dyslexia), in a sample from an individual, comprising a nucleic acid molecule that specifically detects an alteration in the human DCDC2 gene that is associated with reading disability in humans. 
     
     
         2 . The polynucleotide of  claim 1 , wherein the polynucleotide is a probe that hybridizes, under highly stringent conditions, to a mutation in the human DCDC2 gene that is associated with reading disability in humans. 
     
     
         3 . The probe of  claim 2 , wherein the alteration is a deletion in intron 2 of DCDC2 
     
     
         4 . The probe of  claim 3 , wherein the deletion comprises 2,445 bp in intron 2. The probe of  claim 2 , wherein the probe is a DNA probe. 
     
     
         5 . The probe of  claim 5 , wherein the probe is from about 8 nucleotides to about 500 nucleotides. 
     
     
         6 . The probe of  claim 6 , wherein the probe is from about 10 nucleotides to about 250 nucleotides. 
     
     
         7 . The probe of  claim 5 , wherein the probe comprises one or more non-natural or modified nucleotides. 
     
     
         8 . The probe of  claim 8 , wherein the one or more non-natural or modified nucleotides are radioactive, fluorescently, or chemically labeled nucleotides. 
     
     
         9 . A polynucleotide primer that hybridizes, under highly stringent conditions, adjacent to an alteration in a DCDC2 gene that is associated with susceptibility for developing RD in humans. 
     
     
         10 . The polynucleotide primer of  claim 10 , which hybridizes immediately adjacent to the alteration in the DCDC2 gene. 
     
     
         11 . A pair of polynucleotide primers that specifically detect a variant DCDC2 allele that is associated with susceptibility for developing RD in humans, wherein the first polynucleotide primer hybridizes to one side of an alteration in the variant DCDC2 allele and the second polynucleotide primer hybridizes to the other side of the alteration in the DCDC2 allele. 
     
     
         12 . A pair of polynucleotide primers that hybridize to a region of DNA that comprises an alteration in a variant DCDC2 gene that is associated with susceptibility for developing RD in humans, wherein the polynucleotide primers hybridize to the region in such a manner that the ends of the hybridized primers proximal to the alteration are from about 100 to about 10,000 nucleotides apart. 
     
     
         13 . The pair of polynucleotide primers of  claim 11 , wherein the alteration is an intronic polymorphic deletion or an allele of dbSTS ID 808238 within the region of DCDC2 that spans the intronic polymorphic deletion. 
     
     
         14 . The pair of polynucleotide primers of  claim 14 , wherein the intronic polymorphic deletion is approximately 2,445 bp. 
     
     
         15 . The pair of polynucleotide primers of  claim 11 , wherein the primers are DNA primers. 
     
     
         16 . The pair of polynucleotide primers of  claim 16 , wherein the primers are each from about 8 nucleotides to about 500 nucleotides. 
     
     
         17 . The pair of polynucleotide primers of  claim 15 , wherein the primers are each from about 10 nucleotides to about 250 nucleotides. 
     
     
         18 . The pair of polynucleotide primers of  claim 15 , wherein the primers comprise one or more non-natural or modified nucleotides. 
     
     
         19 . The pair of polynucleotide primers of  claim 18 , wherein the one or more non-natural or modified nucleotides are radioactive or fluorescently labeled nucleotides. 
     
     
         20 . A method of detecting, in a sample obtained from an individual, a variant DCDC2 gene that is associated with susceptibility for developing RD in humans, comprising:
 (a) combining the sample with a polynucleotide probe that hybridizes, under highly stringent conditions, to an alteration in DCDC2 associated with susceptibility for developing RD in humans, but not to a wild type DCDC2 gene; and   (b) determining whether hybridization occurs,   wherein the occurrence of hybridization indicates that a variant DCDC2 gene that is associated with susceptibility for developing RD in humans is present in the sample.   
     
     
         21 . A method of detecting, in a sample obtained from an individual, a variant DCDC2 gene that is associated with susceptibility for developing RD in humans, comprising:
 (a) combining the sample with a polynucleotide probe that hybridizes, under highly stringent conditions, to variant DCDC2 gene that is associated with susceptibility for developing RD in humans, thereby producing a combination;   (b) maintaining the combination produced in step (a) under highly stringent hybridization conditions; and   (c) comparing hybridization that occurs in the combination with hybridization in a control, wherein the control is a polynucleotide probe that does not bind to a variant DCDC2 gene that is associated with susceptibility for developing RD in humans or binds only to a wild type DCDC2 gene, and the sample is the same type of sample as in (a) and is treated the same as the sample in (a), and wherein the occurrence of hybridization in the combination but not in the control indicates that a variant DCDC2 gene that is associated with susceptibility for developing RD in humans is present in the sample.   
     
     
         22 . The method of  claim 21 , wherein the extent of hybridization is determined in step (c). 
     
     
         23 . A method of detecting, in a sample obtained from an individual, a variant DCDC2 gene that is associated with susceptibility for developing RD in humans, comprising:
 (a) combining a first portion of the sample with a polynucleotide probe that hybridizes, under highly stringent conditions, to an alteration in the variant DCDC2 that is associated with susceptibility for developing RD in humans;   (b) combining a second portion of the sample with a polynucleotide probe that hybridizes, under highly stringent conditions, to a wild type DCDC2 gene; and   (c) determining whether hybridization occurs,   wherein the occurrence of hybridization in the first portion but not in the second portion indicates that the variant DCDC2 gene is present in the sample.   
     
     
         25 . The method of claim  24 , wherein the alteration is an intronic polymorphic deletion of DCDC2 or an allele of dbSTS 808238 within the region that the deletion spans. 
     
     
         26 . The method of  claim 25 , wherein the intronic polymorphic deletion of DCDC2 is all or a portion of a 2,445 bp deletion in intron 2 of DCDC2. 
     
     
         27 . The method of claim  24 , wherein the sample comprises cells obtained from blood, tears, saliva, mucus, urine, epidermis, epithelium or eye tissue. 
     
     
         28 . The method of claim  24 , wherein the polynucleotide probe is a DNA probe. 
     
     
         29 . The method of claim  24 , wherein the polynucleotide probe is from about 8 nucleotides to about 500 nucleotides. 
     
     
         30 . A method of detecting, in a sample obtained from an individual, a variant DCDC2 gene that is associated with susceptibility for developing RD in humans, comprising:
 (a) combining the sample with a pair of polynucleotide primers, wherein the first polynucleotide primer hybridizes to one side of DNA that is present in a DCDC2 gene associated with susceptibility for developing RD but not present in a DCDC2 gene not associated with susceptibility for developing RD and the second polynucleotide primer hybridizes to the other side of DNA that is present in a DCDC2 gene associated with susceptibility for developing RD, but not present in a DCDC2 gene not associated with susceptibility for developing RD;   (b) amplifying DNA in the sample, thereby producing amplified DNA;   (c) sequencing amplified DNA; and   (d) detecting in the amplified DNA the presence of DNA that is associated with susceptibility for developing RD in humans,   whereby a gene that is associated with susceptibility for developing RD in humans is detected.   
     
     
         31 . A method of identifying or aiding in identifying an individual at risk for developing RD, comprising assaying a sample obtained from the individual for the presence of a DCDC2 gene that is associated with susceptibility for developing RD in humans, wherein the presence of a DCDC2 gene that is associated with susceptibility for developing RD in humans indicates that the individual is at risk for developing RD. 
     
     
         32 . A method of identifying or aiding in identifying an individual at risk for developing RD, comprising:
 (a) combining a sample obtained from the individual with a polynucleotide probe that hybridizes, under highly stringent conditions, to an alteration in a DCDC2 gene that is associated with susceptibility for developing RD, but does not hybridize to a wild type DCDC2 gene; and   (b) determining whether hybridization occurs,   wherein the occurrence of hybridization indicates that the individual is at risk for developing RD.   
     
     
         33 . A method of identifying or aiding in identifying an individual at risk for developing RD, comprising:
 (a) obtaining DNA from the individual;   (b) sequencing a region of the DNA that comprises an alteration in a DCDC2 gene that is associated with susceptibility for developing RD; and   (c) determining whether the alteration is present in DNA obtained from the individual, is present in the DNA,   wherein the presence of the alteration indicates that the individual is at risk for developing RD.   
     
     
         34 . A diagnostic kit for detecting a DCDC2 gene associated with susceptibility for developing RD in a sample from an individual, comprising:
 (a) at least one container means having disposed therein a polynucleotide probe that hybridizes, under highly stringent conditions, to variant DCDC2 DNA associated with susceptibility for developing RD in humans; and   (b) a label and/or instructions for the use of the diagnostic kit in the detection of variant DCDC2 DNA in a sample.   
     
     
         35 . A diagnostic kit for detecting variant DCDC2 DNA in a sample from an individual, comprising:
 (a) at least one container means having disposed therein a polynucleotide primer that hybridizes, adjacent to one side of an alteration in variant DCDC2 DNA that is associated with susceptibility for developing RD in humans; and   (b) a label and/or instructions for the use of the diagnostic kit in the detection of an alteration in variant DCDC2 DNA in a sample.   
     
     
         36 . The diagnostic kit of  claim 35 , additionally comprising a second polynucleotide primer that hybridizes, to the other side of the alteration in the variant DCDC2 DNA.