US2003129626A1PendingUtilityA1

Methods, kits and compositions pertaining to the suppression of detectable probe binding to randomly distributed repeat sequences in genomic nucleic acid

Priority: Sep 24, 2001Filed: Sep 24, 2002Published: Jul 10, 2003
Est. expirySep 24, 2021(expired)· nominal 20-yr term from priority
C12Q 1/6832C12Q 1/6837C12Q 1/6876C12Q 2600/156
57
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Claims

Abstract

This invention is directed to methods, kits, non-nucleotide probes as well as other compositions pertaining to the suppression of binding of detectable nucleic acid probes to undesired nucleotide sequences of genomic nucleic acid in assays designed to determine target genomic nucleic acid.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A non-nucleotide probe of at least sixteen nucleobase containing subunits in length having an aggregate nucleobase sequence that is at least eighty percent homologous to a sixteen nucleotide segment of randomly distributed repeat sequence of genomic nucleic acid.  
     
     
         2 . The non-nucleotide probe of  claim 1 , wherein the segment of randomly distributed repeat sequence is a SINE or LINE selected from the group consisting of: Alu-repeat, Kpn-repeat, di-nucleotide repeat, tri-nucleotide repeat, tetra-nucleotide repeat, penta-nucleotide repeat and hexa-nucleotide repeat.  
     
     
         3 . The non-nucleotide probe of  claim 2 , wherein the segment of randomly distributed repeat sequence contains at least ten consecutive nucleobases that are at least eighty percent homologous to a unit repeat consensus Alu-repeat sequence selected from the group consisting of: Seq. Id. No. 1 and Seq. Id. No. 2.  
     
     
         4 . The non-nucleotide probe of  claim 3 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified consensus sequences.  
     
     
         5 . The non-nucleotide probe of  claim 4 , wherein the ten consecutive nucleobases are exactly homologous to the identified consensus sequences.  
     
     
         6 . The non-nucleotide probe of  claim 1 , wherein the non-nucleotide probe is a peptide nucleic acid probe.  
     
     
         7 . The non-nucleotide probe of  claim 6 , wherein the PNA subunits of the non-nucleotide probe have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases and substituted and unsubstituted aromatic moieties.  
 
       
     
     
         8 . The non-nucleotide probe of  claim 6 , wherein the PNA subunits of the non-nucleotide probe consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         9 . The non-nucleotide probe of  claim 1 , wherein the non-nucleotide probe is from about 16 to about 50 nucleobase containing subunits in length.  
     
     
         10 . A non-nucleotide probe containing an aggregate nucleobase sequence of at least ten consecutive nucleobases that is at least eighty percent homologous to the sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26.  
     
     
         11 . The non-nucleotide probe of  claim 10 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified sequences.  
     
     
         12 . The non-nucleotide probe of  claim 10 , wherein the ten consecutive nucleobases are exactly homologous to the identified sequences.  
     
     
         13 . The non-nucleotide probe of  claim 10 , wherein the non-nucleotide probe is identical in nucleobase sequence to any one of the identified sequences.  
     
     
         14 . The non-nucleotide probe of  claim 10 , wherein the non-nucleotide probe is a peptide nucleic acid probe.  
     
     
         15 . The non-nucleotide probe of  claim 14 , wherein the PNA subunits of the non-nucleotide probe have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases and substituted and unsubstituted aromatic moieties.  
 
       
     
     
         16 . The non-nucleotide probe of  claim 14 , wherein the PNA subunits of the probe consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         17 . The non-nucleotide probe of  claim 10 , wherein the non-nucleotide probe is from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         18 . A mixture of two or more non-nucleotide probes wherein each probe contains an aggregate nucleobase sequence that is at least eighty percent homologous to a sixteen nucleotide segment of randomly distributed repeat sequence of genomic nucleic acid.  
     
     
         19 . The probe mixture of  claim 18 , wherein the segment of randomly distributed repeat sequence is a SINE or LINE selected from the group consisting of: Alu-repeat, Kpn-repeat, di-nucleotide repeat, tri-nucleotide repeat, tetra-nucleotide repeat, penta-nucleotide repeat and hexa-nucleotide repeat.  
     
     
         20 . The probe mixture of  claim 18 , wherein the segment of at least one non-nucleotide probe of the mixture is selected to be at least eighty percent homologous to a consensus unit repeat sequence of known randomly distributed repeat sequence of the genomic nucleic acid.  
     
     
         21 . The probe mixture of  claim 18 , wherein the segment of at least one non-nucleotide probe of the mixture is selected to be at least ten consecutive nucleobases that are at least eighty percent homologous to the nucleobase sequences selected from the group consisting of: Seq. Id. No. 1 and Seq. Id. No. 2.  
     
     
         22 . The probe mixture of any of claims  20  or  21 , wherein the ten consecutive nucleobases of each non-nucleotide probe are at least ninety percent homologous to the identified sequences.  
     
     
         23 . The probe mixture of any of claims  20  or  21 , wherein the ten consecutive nucleobases are exactly homologous to the identified sequences.  
     
     
         24 . The probe mixture of  claim 18 , wherein the one or more non-nucleotide probes are peptide nucleic acid oligomers.  
     
     
         25 . The probe mixture of  claim 24 , wherein the PNA subunits of the individual PNA probes have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases, substituted and unsubstituted aromatic moieties, biotin and fluorescein.  
 
       
     
     
         26 . The probe mixture of  claim 24 , wherein the PNA subunits of the individual PNA probes consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         27 . The probe mixture of  claim 18 , wherein the individual probes are from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         28 . The probe mixture of  claim 18 , wherein the mixture contains from about 5 to about 50 probes of different nucleobase sequence.  
     
     
         29 . The probe mixture of  claim 18 , wherein the mixture contains from about 10 to about 25 probes of different nucleobase sequence.  
     
     
         30 . The probe mixture of  claim 18 , wherein the mixture comprises at least one non-nucleotide probe containing an aggregate nucleobase sequence of at least ten consecutive nucleobases that is at least eighty percent homologous to the nucleobase sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26.  
     
     
         31 . The probe mixture of  claim 30 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified sequences.  
     
     
         32 . The probe mixture of  claim 30 , wherein the ten consecutive nucleobases are exactly homologous to the identified sequences.  
     
     
         33 . The probe mixture of  claim 30 , wherein the probe is identical in nucleobase sequence to any one of the identified sequences.  
     
     
         34 . The probe mixture of  claim 30 , wherein all non-nucleotide probes of the mixture are peptide nucleic acid oligomers.  
     
     
         35 . The probe mixture of  claim 18 , further comprising one or more detectable nucleic acid probes.  
     
     
         36 . The probe mixture of  claim 35 , further comprising genomic nucleic acid of a sample to be tested.  
     
     
         37 . A composition comprising: 
 a) genomic nucleic acid containing one or more segments of randomly distributed repeat sequence selected from the group consisting of: SINEs and LINEs; and    b) two or more non-nucleotide probes of different nucleobase sequence hybridized to at least a fraction of the one or more segments of randomly distributed repeat sequence of the genomic nucleic acid.    
     
     
         38 . A composition comprising: 
 a) a detectable nucleic acid probe of at least 100 bp that has been derived from genomic nucleic acid and that contains one or more segments of randomly distributed repeat selected from the group consisting of: SINEs and LINEs; and    b) two or more non-nucleotide probes of different nucleobase sequence hybridized to at least a fraction of the one or more segments of randomly distributed repeat sequence of the detectable nucleic acid probe.    
     
     
         39 . The composition of any of claims  37  or  38 , wherein the randomly distributed repeat sequence is selected from the group consisting of: Alu-repeats, Kpn-repeats, di-nucleotide repeats, tri-nucleotide repeats, tetra-nucleotide repeats, penta-nucleotide repeats and hexa-nucleotide repeats.  
     
     
         40 . The composition of any of claims  37  or  38 , wherein the one or more segments of randomly distributed repeat sequence are a fraction, or part, of a unit repeat of either: 
 i) an Alu-repeat sequence; or  
 ii) a consensus sequence of a Alu-repeat sequence.  
 
     
     
         41 . The composition of  claim 37 , wherein the genomic nucleic acid comprises complementary strands of randomly distributed repeat sequence.  
     
     
         42 . The composition of any of claims  37  or  38 , wherein one or more of the non-nucleotide probes contain a segment of at least ten consecutive nucleobases that is at least eighty percent homologous to the sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26.  
     
     
         43 . The composition of  claim 42 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified sequences.  
     
     
         44 . The composition of  claim 42 , wherein the ten consecutive nucleobases are one hundred percent homologous to the identified sequences.  
     
     
         45 . The composition of  claim 42 , wherein the probes have exactly the identified nucleobase sequences.  
     
     
         46 . The composition of  claim 37 , wherein the genomic nucleic acid is contained in a fixed tissue or a cell.  
     
     
         47 . The composition of  claim 37 , wherein the genomic nucleic acid is contained in metaphase spreads, interphase nuclei or nuclei found in paraffin embedded tissue material or frozen tissue sections.  
     
     
         48 . The composition of any of claims  37  or  38 , wherein the two or more non-nucleotide probes are peptide nucleic acid oligomers.  
     
     
         49 . The composition of  claim 48 , wherein the PNA subunits of the individual PNA probes have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases, substituted and unsubstituted aromatic moieties, biotin and fluorescein.  
 
       
     
     
         50 . The composition of  claim 48 , wherein the PNA subunits of the individual PNA probes consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         51 . The composition any of claims  37  or  38 , wherein the composition contains from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.  
     
     
         52 . The composition any of claims  37  or  38 , wherein the composition contains from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.  
     
     
         53 . A method for suppressing the binding of one or more detectable nucleic acid probes, that are greater than 100 bp and that have been derived from genomic nucleic acid, to one or more undesired sequences in an assay for determining target genomic nucleic acid of a sample; said method comprising: 
 a) contacting the sample with a mixture of two or more non-nucleotide probes wherein each probe contains an aggregate nucleobase sequence that is at least eighty percent homologous to a segment of randomly distributed repeat sequence of genomic nucleic acid;    b) contacting the sample with the one or more detectable nucleic acid probes; and    c) determining the target genomic nucleic acid of the sample by determining the hybridization of the one or more detectable nucleic acid probes to the target genomic nucleic acid of the sample.    
     
     
         54 . The method of  claim 53 , wherein the randomly distributed repeat sequence is selected from the group consisting of: SINEs and LINEs.  
     
     
         55 . The method of  claim 54 , wherein the randomly distributed repeat sequence is selected from the group consisting of: Alu-repeats, Kpn-repeats, di-nucleotide repeats, tri-nucleotide repeats, tetra-nucleotide repeats, penta-nucleotide repeats and hexa-nucleotide repeats.  
     
     
         56 . The method of  claim 55 , wherein the nucleobase sequence of the non-nucleotide probe contains a segment of at least ten consecutive nucleobases that is at least eighty percent homologous to a fraction of the consensus unit repeat Alu-repeat sequences selected from the group consisting of: Seq. Id. No. 1 and Seq. Id. No. 2.  
     
     
         57 . The method of  claim 56 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified consensus sequences.  
     
     
         58 . The method of  claim 56 , wherein the ten consecutive nucleobases are exactly homologous to the identified consensus sequences.  
     
     
         59 . The method of  claim 53 , wherein the two or more non-nucleotide probes are peptide nucleic acid oligomers.  
     
     
         60 . The method of  claim 59 , wherein the PNA subunits of the PNA probes have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases and substituted and unsubstituted aromatic moieties.  
 
       
     
     
         61 . The method of  claim 59 , wherein the PNA subunits of the PNA probes consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         62 . The method of  claim 53 , wherein the one or more non-nucleotide probes or the mixture contain a segment of at least ten consecutive nucleobases that is at least eighty percent homologous to the sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. 20, No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26.  
     
     
         63 . The method of  claim 62 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified sequences.  
     
     
         64 . The method of  claim 62 , wherein the ten consecutive nucleobases are exactly homologous to the identified sequences.  
     
     
         65 . The method of  claim 62 , wherein the probe is identical in nucleobase sequence to the identified sequences.  
     
     
         66 . The method of  claim 53 , wherein the genomic nucleic acid is contained in a fixed tissue or a cell.  
     
     
         67 . The method of  claim 53 , wherein the sample is selected from the group consisting of: metaphase spreads, interphase nuclei, nuclei found in paraffin embedded tissue material or frozen tissue sections.  
     
     
         68 . The method of  claim 53 , wherein the non-nucleotide probes are from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         69 . The method of  claim 53 , wherein the mixture contains from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.  
     
     
         70 . The method of  claim 53 , wherein the mixture contains from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.  
     
     
         71 . A method for comparing a sample of genomic nucleic acid with that of a control sample using a genomic nucleic acid reference array, said method comprising: 
 a) providing a sample of genomic nucleic acid to be tested;    b) providing a control of genomic nucleic acid, wherein the control and the sample are differentially labeled;    c) providing a genomic nucleic acid reference array;    d) providing a mixture of two or more non-nucleotide probes wherein each probe contains an aggregate nucleobase sequence that is at least eighty percent homologous to a sixteen nucleotide segment of randomly distributed repeat sequence of genomic nucleic acid;    e) treating the sample and control genomic nucleic acid, the array or both the sample and control genomic nucleic acid and the array with the mixture of non-nucleotide probes under suitable hybridization conditions;    f) contacting the array with the treated mixture of sample and control genomic nucleic acid under suitable hybridization conditions; and    g) comparing the intensities of the signals from the differential labels of the array to caused by hybridization of the probes to genomic nucleic acid thereby determine one or more variations in copy numbers of sequences in the sample as compared with the relative copy numbers of substantially identical sequences in the control.    
     
     
         72 . The method of  claim 71 , wherein hybridization on the genomic array is determined using an intercalating dye that is specific for a nucleic acid/nucleic acid hybrid.  
     
     
         73 . The method of  claim 71 , wherein hybridization on the genomic array is determined using a detectable antibody, or antibody fragment, that is specific for a nucleic acid/nucleic acid hybrid.  
     
     
         74 . The method of  claim 71 , wherein the sample of genomic nucleic acid to be tested and, as appropriate, the reference sample of genomic nucleic acid are labeled with a detectable moiety such that hybridization on the genomic array is determined by determining the presence, absence, amount or location of the detectable label on said one or more genomic arrays.  
     
     
         75 . The method of  claim 71 , wherein the genomic array comprises nucleic acid that is prepared from BAC clones.  
     
     
         76 . The method of  claim 71 , wherein one or more of the non-nucleotide probes of the mixture contain an aggregate nucleobase sequence of at least ten consecutive nucleobases that is at least eighty percent homologous to the consensus Alu-repeat sequences selected from the group consisting of: Seq. Id. No. 1 and Seq. Id. No. 2.  
     
     
         77 . The method of  claim 76 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified consensus sequences.  
     
     
         78 . The method of  claim 76 , wherein the ten consecutive nucleobases are exactly homologous to the identified consensus sequences.  
     
     
         79 . The method of  claim 71 , wherein the non-nucleotide probes of the mixture are peptide nucleic acid oligomers.  
     
     
         80 . The method of  claim 79 , wherein the PNA subunits of the PNA probes have the formula:  
       
         
           
           
               
               
           
         
         wherein, 
 each J is the same or different and is selected from the group consisting of: H, R 1 , OR 1 , SR 1 , NHR 1 , NR 1   2 , F, Cl, Br and I;  
 each K is the same or different and is selected from the group consisting of: O, S, NH and NR 1 ;  
 each R 1  is the same or different and is an alkyl group having one to five carbon atoms which may optionally contain a heteroatom or a substituted or unsubstituted aryl group;  
 each A is selected from the group consisting of a single bond, a group of the formula; —(CJ 2 ) s — and a group of the formula; —(CJ 2 ) s C(O)— wherein, J is defined above and each s is an integer from one to five;  
 each t is 1 or 2;  
 each u is 1 or 2; and  
 each L is the same or different and is independently selected from the group consisting of J, dabcyl, fluorescein, adenine, cytosine, guanine, thymine, uridine, 5-methylcytosine, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudoisocytosine, 2-thiouracil, 2-thiothymidine, other naturally occurring nucleobase analogs, other non-naturally occurring nucleobases and substituted and unsubstituted aromatic moieties.  
 
       
     
     
         81 . The method of  claim 79 , wherein the PNA subunits of the PNA probes consist of a naturally or non-naturally occurring nucleobase attached to an aza nitrogen of an N-[2-(aminoethyl)]glycine backbone through a methylene carbonyl linkage.  
     
     
         82 . The method of  claim 71 , wherein one or more non-nucleotide probes of the mixture contain a segment of at least ten consecutive nucleobases that is at least eighty percent homologous to the sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26.  
     
     
         83 . The method of  claim 82 , wherein the ten consecutive nucleobases are at least ninety percent homologous to the identified sequences.  
     
     
         84 . The method of  claim 82 , wherein the ten consecutive nucleobases are exactly homologous to the identified sequences.  
     
     
         85 . The method of  claim 82 , wherein the probe is identical in nucleobase sequence to the identified sequences.  
     
     
         86 . The method of  claim 71 , wherein the non-nucleotide probes are from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         87 . The method of  claim 71 , wherein the mixture contains from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.  
     
     
         88 . The method of  claim 71 , wherein the mixture contains from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.  
     
     
         89 . A method for determining non-nucleotide probes that hybridize to randomly distributed repeat sequences and that are suitable for suppressing the binding of a detectable nucleic acid probe, that is greater than 100 bp in length and that is derived from genomic nucleic acid, to one or more undesirable sequences in an assay for determining target genomic nucleic acid of a sample; said method comprising: 
 a) designing possible nucleobase sequences of non-nucleotide probes using sequence alignment of available sequence data for randomly distributed repeat sequences;    b) preparing labeled non-nucleotide probes having said possible nucleobase sequences;    c) treating genomic nucleic acid of a sample that contains the target genomic nucleic acid with the labeled non-nucleotide probes under suitable hybridization conditions;    d) determining the relative signal of the hybridized labeled probes of the many different possible nucleobase sequences;    e) selecting the probe or probes that exhibit the strongest signal as a result of binding to the genomic nucleic acid; and    f) testing the selected non-nucleotide probe or probes to thereby determine whether or not they are suitable for suppressing the undesired binding of a detectable nucleic acid probe of greater than 100 bp in length that is derived from genomic nucleic acid to one or more non-target sequences in an assay for determining target genomic nucleic acid of a sample.    
     
     
         90 . The method of  claim 89 , wherein testing comprises determining the R-banding potential and signal intensity.  
     
     
         91 . A reagent kit comprising: 
 a) a mixture of two or more non-nucleotide probes containing at least sixteen consecutive nucleobases that are at least eighty percent homologous to a fraction of the unit repeat Alu-repeat consensus sequence selected from the group consisting of: Seq. Id. No. 1 and Seq. Id. No. 2; and    b) other reagents and compositions suitable for performing an assay to thereby determine genomic nucleic acid of a sample.    
     
     
         92 . The reagent kit of  claim 91  further comprising: 
 c) one or more detectable nucleic acid probes of greater than 100 bp in length and that are derived from genomic nucleic acid.  
 
     
     
         93 . The reagent kit of  claim 92 , wherein the one or more detectable nucleic acid probes are provided in the container that contains the mixture of two or more non-nucleotide probes.  
     
     
         94 . The reagent kit of  claim 92 , wherein the non-nucleotide probes are from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         95 . The reagent kit of  claim 92 , wherein the mixture contains from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.  
     
     
         96 . The reagent kit of  claim 92 , wherein the mixture contains from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.  
     
     
         97 . A kit comprising: 
 a) a mixture of two or more non-nucleotide probes wherein at least one probe contains a segment of at least ten consecutive nucleobases that are at least eighty percent homologous to the Alu-repeat sequences selected from the group consisting of: Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25 and Seq. Id. No. 26; and    b) other reagents and compositions for performing a assay to thereby determine genomic nucleic acid of a sample.    
     
     
         98 . The kit of  claim 97  further comprising: 
 c) one or more detectable nucleic acid probes of greater than 100 bp in length and that are derived from genomic nucleic acid.  
 
     
     
         99 . The kit of  claim 97 , wherein the one or more detectable nucleic acid probes are provided in a container that contains the mixture of two or more non-nucleotide probes.  
     
     
         100 . The kit of  claim 97 , wherein the non-nucleotide probes are from about 10 to about 50 nucleobase containing subunits in length.  
     
     
         101 . The kit of  claim 99 , wherein the mixture contains from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.  
     
     
         102 . The kit of  claim 99 , wherein the mixture contains from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.

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