Mitochondrial Disease Genetic Diagnostics

Abstract

Mitochondrial disease genetic diagnostics and methods of use thereof.

What is claimed is: 
     
         1 . A composition comprising oligonucleotides that specifically hybridize with the nuclear genome and at least one oligonucleotide that specifically hybridizes with mitochondrial DNA, wherein said oligonucleotide that specifically hybridizes with mitochondrial DNA comprises a nucleic acid molecule in  FIG. 6 . 
     
     
         2 . The composition of  claim 1 , wherein said oligonucleotides that specifically hybridize with the nuclear genome comprise a whole exome library. 
     
     
         3 . The composition of  claim 1 , comprising at least 100 of the nucleic acid molecules provided in  FIG. 6 . 
     
     
         4 . The composition of  claim 1 , comprising all of the nucleic acid molecules provided in  FIG. 6 . 
     
     
         5 . The composition of  claim 1 , wherein said composition comprises oligonucleotides that specifically hybridize with MitoCarta gene sequences. 
     
     
         6 . The composition of  claim 5 , wherein said composition comprises oligonucleotides that specifically hybridize with at least one gene selected from the group consisting of BCL2, GPX1, LYRM4, MSRB2, NDUFA11, NUDT8, PIGY, PRDX2, PRDX5, SLC25A26, TIMM117B, ZBED5, C6orf136, HSD17B8, MRPS18B, and TAP1. 
     
     
         7 . The composition of  claim 1 , wherein ratio of oligonucleotides which specifically hybridize with mitochondrial DNA to oligonucleotides which specifically hybridize with the nuclear genome is about 1:75 to about 1:150. 
     
     
         8 . The composition of  claim 7 , wherein said ratio is about 1:100. 
     
     
         9 . The composition of  claim 1 , wherein said oligonucleotides are about 20 to about 250 nucleotides in length. 
     
     
         10 . A composition comprising at least one oligonucleotide that specifically hybridizes with mitochondrial DNA, wherein said oligonucleotide comprises a nucleic acid molecule in  FIG. 6 . 
     
     
         11 . The composition of  claim 10 , comprising at least 100 of the nucleic acid molecules provided in  FIG. 6 . 
     
     
         12 . The composition of  claim 10 , comprising all of the nucleic acid molecules provided in  FIG. 6 . 
     
     
         13 . The composition of  claim 10 , wherein said composition comprise oligonucleotides that specifically hybridize with MitoCarta gene sequences. 
     
     
         14 . The composition of  claim 13 , wherein said composition comprises oligonucleotides that specifically hybridize with at least one gene selected from the group consisting of BCL2, GPX1, LYRM14, MSRB2, NDUFA11, NUDT8, PIGY, PRDX2, PRDX5, SLC25A26, TIMMI17B, ZBED5, C6orf136, HSD17B8, MRPS18B, and TAP1. 
     
     
         15 . A kit comprising the composition of  claim 10 . 
     
     
         16 . The kit of  claim 15 , further comprising oligonucleotides that specifically hybridize with the nuclear genome, optionally contained in a separate composition. 
     
     
         17 . A method for detecting genetic mutations associated with a mitochondrial disease, said method comprising
 a) isolating nucleic acid molecules in a biological sample with at least one oligonucleotide that specifically hybridizes with mitochondrial DNA, wherein said oligonucleotide comprises a nucleic acid molecule in  FIG. 6 ;   b) amplifying the isolated nucleic acid molecules, and   c) determining the presence or absence of mutation associated with a mitochondrial disease in the amplified DNA.