Patent Publication Number: US-2004053320-A1

Title: Hybridization probes derived from the spacer region between the 16S and 23S rRNA genes for the detection of non-viral microorganisms

Description:
[0001] The invention relates to nucleic acid probes derived from the spacer region between the ribosomal ribonucleic acid (rRNA) gene, particularly between the 16S and 23S rRNA genes, to be used for the specific detection of non-viral organisms in a biological sample by a hybridization procedure.  
       [0002] Although much progress has been made in the last decade, for many microorganisms the diagnostic procedures currently in use are still laborious, nonsensitive and aspecific. Many of these pitfalls can be overcome by using nucleic acid probes. These nucleic acid probes can, for instance, be total genomic deoxyribonucleic acid (DNA), plasmids, riboprobes or synthetic oligonucleotides and these probes may target the genomic DNA or messenger or stable RNA species present in biological samples. Although not necessary, the use of synthetic oligonucleotides is preferred. Oligonucleotides can be rapidly synthesized in large amounts using chemical methods, have a long shelf-life, and are easily purified and labeled.  
       [0003] For a reliable diagnosis of microorganisms using DNA-probe technology the probes used should be highly specific (i.e. they should not cross-react with nucleic acids from other organisms) and highly sensitive (i.e. most, if not all, strains of the organism to be detected should react with the probe). Hence, the preferred target sequences should have the following characteristics:  
       [0004] (i) The sequence should be present in the genome of each strain of the organism c ncerned.  
       [0005] (ii) The evolutionary diversity of the sequence should be such that, on the one hand, there is sufficient sequence-diversity to allow differentiation of the species concerned from other closely related species and, on the other hand, sufficient sequence-conservation to allow the detection of all strains of the species concerned with the probe used.  
       [0006] Species-specific probes have been described for a large number of organisms. For a recent review see Tenover, Clin. Microbiol. Rev. 1:82-101, 1988.  
       [0007] However, it is not obvious from which gene in the genome that specific probe sequences can be derived. In probe development often large selection procedures have to be followed to obtain fragments which at last turn out to be specific for the organism under investigation (Korolik et al., J. Gen. Microbiol. 134:521-529, 1988; Grimont et al., J. Clin. Microbiol. 21:431-437, 1985; Welcher et al., Nucl. Acids Res. 14:10027-10044, 1986; Donegan et al., Mol. Cell. Probes 3:13-26, 1989; Beaulieu and ROY, Abstract nr D249, Abstracts of the Annual Meeting of the American Society for Microbiology, 1989). Most often the function or identity of the gene from which the specific fragment derives is not known and the screening procedure has to be blindly repeated each time another specific probe is wanted. The precise identification of a gene which meets the criteria listed above and which is ubiquitously present would obviate the need for time-consuming and tedious selections.  
       [0008] The 16S or 23S rRNA genes are quite often used for probe development since sequences can easily be obtained using described methods and it is known that variable regi ns exist within these highly conserved genes which can be used for species-specific detection. However, for certain organisms it may not be possible to d rive highly specific and sensitiv probes from the 16S and 23S rRNA gen s, for instance, because their evolutionary nucleic acid sequence conservation is too high. Another consequence of the conserved character of these genes is that the differentiation of two organisms is often based on one or a few mismatches only in the target sequence which puts constraints on the stringency of the hybridization. A slight deviation from these conditions may result in misidentification.  
       [0009] Therefore the characterization of a ubiquitous gene which allows the development of species-specific probes for most organisms including those for which it was not possible to infer specific probes from the 16S and 23S rRNA genes, and which preferably have a broader stringency-range, would be extremely advantageous.  
       [0010] Each cellular organism possesses ribosomal RNA cistrons since its transcripts are essential for the function of ribosomes and the synthesis of proteins. In general the genes are present in multiple copies in the genome. In eubacteria the 16S rRNA gene (also called small subunit rRNA (rRNA)] is found at the 5′ end of the rRNA cistron, followed by the 23S rRNA [also call d large subunit rRNA(lrRNA)]. The 5S rRNA gene is located at the 3′ end of the cistron. The 16S, 23S and SS genes are separated by spacer regions in which transfer RNA (tRNA) genes and signal sequences involved in post-transcriptional processing may be found. At first the rRNA cistron is transcribed as one precursor RNA molecule. This primary transcript is further processed by endo- and exoribonucleases to its mature products. As a consequence, spacer region sequences are not exclusively present in the genome of the organism but also in precursor RNA molecules and processing products. The structure and processing of eubacterial rRNA cistr ns is discussed in detail in the f llowing reference: Gegenheimer and Apirion, Microbiol. Rev. 45:502-541, 1981.  
       [0011] The situation in nuclear genomes of eukaryotes somewhat differs in that a 5.8S RNA gene is located between the srRNA and lrRNA and 5S rRNA genes are arranged in separate long tandem arrays (Perry, Annu. Rev. Biochem. 45:605-629, 1976; Long and Dawid, Annu. Rev. Biochem. 49:727-764, 1980.). However, rRNA costrons in the mitochondria or chloroplasts of eukaryotic organisms are prokaryotic in nature (Borst and Grivell, Nature 290:443-444, 1981).  
       [0012] The nucleic acid sequence of the spacer region of only a very limited number of eukaryotic or prokaryotic organisms is available from the literature (e.g. Young et al., J. Biol. Chem. 254:3264-3271, 1979; and Martens et al., System. Appl. Microbiol. 9:224-230, 1987.). From these data no reliable estimation of the nucleic acid sequence conservation can be made and consequently nothing can be concluded concerning the suitability of the spacer region for the selection of specific probes.  
       [0013] More precisely, concerning prokaryotes, hybridization probes derived from the spacer region between the 16S and 23S rRNA genes for the detection of microorganisms in a biological sample have not yet been described. Neither are they known for the corresponding spacer region between the small and large subunit rRNA genes of eukaryotes.  
       [0014] As far as eukaryotes are concerned, the use of a cloned fragment from a ribosomal gene spacer has been described in a taxonomical study on Leishmania (Ramirez and Guevara, Mol. Bioch. Parasitol. 22:177-183, 1987). However, the region used as well as the approach of the study are of no help to the man skilled in the art, for using a pr be derived from the spacer region between th small rRNA and large rRNA genes, particularly for the following reasons:  
       [0015] (i) the ribosomal genes spacer used by Ramirez and Guevara is not the spacer region between the srRNA and lrRNA, but refers to the sequence present between two adjacent rRNA cistrons; such spacers are only found in eukaryotes between repeating units of rRNA cistrons and are not related to the internal spacer in between the srRNA and lrRNA genes;  
       [0016] (ii) the differentiation between Leishmania taxa using the gene spacer fragment is achieved by comparing restriction fragment patterns; the fragment used is not specific.  
       [0017] Hence, differentiation with the fragment using a simple hybridization protocol without resorting to Southern blot analysis is not possible.  
       [0018] No evidence is presented that highly specific probes can be found in that ribosomal gene spacer.  
       [0019] Thus, the aim of the invention is to provide species-specific probes derived from the spacer region between rRNA genes for a particular organism such as a bacterial species.  
       [0020] Another object of the invention is to provide DNA probes derived from the 16S-23S rRNA spacer region for the detection of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , and  Campylobacter jejuni  and  Campylobacter coli  strains.  
       [0021] Still, another object of the invention is to provide DNA probes derived from the 16S-23S rRNA gene spacer region for the detection of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptoc ccus agalactiae, Streptococcus pneumoniae , and  Campylobacter jejuni  and  Campylobacter coli  strains in a biological sample by a hybridization test such as a dot-spot, strand-displacement, c mpetiti n, sandwich, or reversed hybridization test. Still another object of the invention is to provide probes and a simple method for the in vitro diagnosis of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , and  Campylobacter jejuni  and  Campylobacter coli  strains.  
       [0022] The invention relates to a probe consisting of at least about 15 nucleotides of the spacer region between rRNA genes of a non-viral organism, particularly of a prokaryotic organism, and more particularly of a bacteria.  
       [0023] The invention relates more particularly to a probe consisting from about 15 nucleotides to about the maximum number of nucleotides of the spacer region, and more preferably from about 15 to about 100 nucleotides of the spacer region between the rRNA genes, particularly between 16S and 23S rRNA genes of a non-viral organism, particularly of prokaryotic organisms, and more particularly of bacteria.  
       [0024] In the following, the expression “spacer region” designates the spacer region between rRNA genes and more particularly between the 16S and 23S rRNA genes.  
       [0025] The invention relates to a probe for use in a hybridization assay, liable to be obtained in the process which comprises constructing an oligonucleotide that is sufficiently complementary to hybridize to a sequence of the spacer region between rRNA genes selected to be unique to non-viral organisms, particularly to prokaryotic organisms, more particularly to bacteria, which are to b detected with said sequence of the spacer region between rRNA genes being selected  
       [0026] either by  
       [0027] comparing the nucleotide sequence of the spacer region between the rRNA genes of the sought organism with the nucleotide sequence of the spacer region between the rRNA genes of the closest neighbours,  
       [0028] selecting a sequence of about at least 15 nucleotides, and preferably from about 15 to about the maximum number of nucleotides of the spacer region and more preferably from about 15 to about 100 nucleotides, of the spacer region between rRNA genes of the sought organism which presents at least one mismatch with the spacer region between the rRNA genes of at least one of the closest neighbours,  
       [0029] or by  
       [0030] deleting, in the spacer region of the organism to be sought, the tRNA genes and possibly the signal sequences, to obtain a shortened spacer region and  
       [0031] determining by trial and error a specific nucleotide sequence of at least about 15 nucleotides, and preferably from about 15 to about the maximum number of nucleotides of the spacer region and more preferably from about 15 to about 100 nucleotides, from the shortened spacer region, said sequence being able to hybridize specifically with the nucleic acids (DNA and/or RNAs) of the sought organism.  
       [0032] The invention relates particularly to a probe wherein the spacer region between rRNA genes is the transcribed spacer regi n between the 16S rRNA gene and the 23S rRNA gene.  
       [0033] The spacer regions of several micr organisms were cloned, sequenced and c mpared as will be outlined later herein. The comparison revealed that the nucleic acid sequence of the spacer region is of a semi-conserved nature, as compared with that of rRNA genes, which are highly conserved. Hence, the spacer region might be better suited for probe development than the rRNA genes itself. FIGS. 1, 2, and  10  illustrate that there is a high degree of sequence homology between highly related organisms (such as highly related strains from the same genospecies). Somewhat more sequence variations were found between moderately related organisms as shown in FIGS. 3 and 7. A total lack of significant sequence homology (except for the tRNA sequences) could be demonstrated between distantly related species, as shown in FIGS.  4  to  6 .  
       [0034] In the Table below, homology values (in % sequence homology) of 16S rRNA sequences of different strains (16S hom) are compared with the corresponding homology values of the spacer regions (spacer hom). The homology values (16S hom and spacer hom) were calculated using the PC Gene software supplied by Intelligentics Inc. and Genofit SA (release 6.01/Apr. 20, 1989). The total number of nucleotides compared is given between parentheses. The results clearly show that the spacer region is less conserved than the 16S rRNA molecule.  
                                                          strains compar d       16S   Spacer                                     strain 1   Strain 2   hom   hom                         N. gonorrhoeae       N. gonorrhoeae     99.9%    100%           NCTC 8375   ITG 4367   (1434)   (335)             B. pertussis       B. bronchiseptica      100%   98.1%           ATCC 10380   NCTC 452    (417)   (582)             N. gonorrhoeae       N. meningitidis       99%   93.5%           NCTC 8375   NCTC 10025   (1452)   (603)             B. catarrhalis       M. nonliquefaciens     97.9%   87.1%           ITG 4197   ATCC 19975   (1244)   (498)             B. pertussis       N. gonorrhoeae     86.3%   58.4%           ATCC 10380   NCTC 8375    (998)   (582)             B. catarrhalis       N. gonorrhoeae     83.8%   68.1%           ITG 4197   NCTC 8375   (1485)   (498)             H. ducreyi       E. coli     88.3%   67.1%           CIP 541       (1498)   (346)                      
 
       [0035] As a result, highly species-specific and sensitive probes could be inferred from the spacer region sequence of the relevant pathogenic species under study, i.e.  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , and  Campylobacter jejuni  and  Campylobacter coli  strains. Valuable probes could als be derived from the spacer region for the species  Neisseria meningitidis  and  B rdetella Pertussis  for which highly specific probes could n t be found in the 16S and/or 23S rRNA molecules. It is very likely that specific probes for other species than those described herein (e.g. other Campylobacter species, other Haemophilus species, Actinobacillus species, Bacteroides species, Chlamydia species, etc.) can be inferred from spacer region sequences as well.  
       [0036] The target of the probes derived from the transcribed spacer region between the 16S and 23S rRNA gene is the genomic DNA and the precursor RNA molecules present in the cells to be detected. The detection of the precursor RNA molecules is advantageous since these molecules are single-stranded and may be present in multiple copies. On the other hand, DNA molecules are much more refractory to enzymatical degradation than RNA molecules. Hence, DNA targeting is preferred when biological samples cannot be processed and/or stored adequately to prevent RNA degradation prior to hybridization.  
       [0037] Another particular advantage of probes derived from the 16S-23S rRNA transcribed spacer regions lies in target detection after enzymatical amplification using the polymerase chain reaction (PCR). The spacer region of many microorganisms can for instance be enzymatically amplified using the same primers allocated in a conserved region of the 3′-end and the 5′-end of the 16S and the 23S rRNA genes respectively. Taking advantage of the highly conserved character of the rRNA genes, spacer regions of many organisms can be amplified, if preferred simultaneously, using the same reagents and protocol and afterwards the amplified fragment can be detected using a probe which specifically targets the spacer region of the rganism of interest. An advantageous meth d f r the simultaneous and specific detecti n of simultaneously amplified fragments is the reversed hybridization.  
       [0038] Since the spacer region is flanked by conserved sequences, the cloning and sequencing of this region with the aid of the PCR technique is simple, and the same protocol can be applied to a great variety of organisms. Hence, the sequences of the spacer regions are obtained by enzymatical amplification of rRNA genes using conserved primers allocated in the 16S or 23S rRNA. Examples of basic primer pairs which can be used for the amplification of fragments spanning the spacer region are:  
                                          Primer pair 1:   TGGCTCAGAT TGAACGCTGG CGGC, and                   CCTTTCCCTC ACGGTACTGG T                       Primer pair 2:   TGGGTGAAGT CGTAACAAGG TA, and               CACGTCCTTC GTCGCCT.          
 
       [0039] The amplified fragment can be cloned as such or as two sub-fragments after digestion with a restriction enzyme recognizing a unique restriction site. A strategy for cloning PCR products in M13 has been described by Medlin et al. (Gene 71:491-499, 1988).  
       [0040] The same strategy can be used for cloning in a plasmid vector. In this approach the basic primers are extended at their 5′-end with a nucleotide sequence comprising an unique restriction site, enabling directional cloning of the fragment. After cloning in a plasmid vector the spacer region can be sequenced using the dideoxy chain-termination method.  
       [0041] This approach is considerably less tedious and time-consuming than the conventional cloning procedures using genomic banks or selected restriction endonucleas fragments.  
       [0042] Although sequence information is mor rapidly obtained when the sequencing reactions are performed directly on PCR fragm nts with ut cloning, the sequence information generated from cloned fragments is more accurate and complete. In contrast to PCR fragments, cloned gene fragments can easily be purified in large amounts, which results in clearly readable sequencing ladders. Since one mismatch in the probe sequence may result in useless probes, accuracy is highly preferred over speed when obtaining sequences.  
       [0043] Taking into account the ease of obtaining spacer sequences with the approach outlined above, nucleotide sequence comparison of the spacer region of the organism for which a probe is desired with the spacer region of the closest neighbour is the preferred way t infer specific probe sequences.  
       [0044] The closest neighbour means the taxon which is known to be most closely related in terms of DNA homology and which has to be differentiated from the organism of interest.  
       [0045] Depending on the taxonomical position of the organism of interest, the closest neighbour may be very highly related to the organism of interest, exhibiting more than 75% degree of binding, or may be rather distantly related showing no significant percentage f DNA homology. In the initial renaturation rate meth d the degree of binding values are insignificant bel w about 30%; in solid phase DNA:DNA hybridization methods, DNA homologies become insignificant between 10 to 20% degree of binding.  
       [0046] However, when the nucleotide sequences of the closest neighbours from which the organism of interest has to be differentiated are not available, the selection of the specific probes can be done by trial and error. In that case, for each particular organism a specific probe region, which may be located anywhere in the spacer region, has t be defined experimentally. Only few areas in th spacer regions, such as tRNA genes or signal sequences can, in certain instances, be excluded a priori as pr be regions. How ver, since 16S-23S rRNA spacer regions in general are small—usually not longer than 900 bp—good probe sequences can be readily found without extensive screening.  
       [0047] By way of example, for a spacer region between the 16S and 23S rRNA gene of 700 bp, the “shortened” spacer region obtained by deleting the tRNA gene and th signal sequence can be of about 500 bp.  
       [0048] The term “a biological sample” as used herein refers to a specimen such as a clinical sample (pus, sputum, blood, urine, etc.), an environmental sample, bacterial colonies, contaminated or pure cultures, purified nucleic acid, etc. in which the target sequence of interest is sought.  
       [0049] “rRNA gene spacer region derived” as used herein refers to the fact that the probes concerned hybridize with sequences located in the spacer region between ribosomal RNA genes normally present in the genome or transcript RNA molecules, no matter whether said probes are themselves formed of DNA or RNA fragments, or whether they consist of cloned fragments (in the case of DNA) or of synthetic oligonucleotides.  
       [0050] A hybridization probe of the invention for detecting  Neisseria gonorrhoeae  strains contains:  
       [0051] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group NGI1:                   CGATGCGTCG TTATTCTACT TCGC   NGI1                       GCGAAGTAGA ATAACGACGC ATCG   NGI1IC                       GCGAAGUAGA AUAACGACGC AUCG   NGI1ICR                       CGAUGCGUCG UUAUUCUACU UCGC   NGI1R                       Group NGI2:           TTCGTTIACC TACCCGTTGA CTAAGTAAGC AAAC   NGI2                       GTTTGCTTAC TTAGTCAACG GGTAGGTAAA CGAA   NGI2IC                       GUUUGCUUAC UUAGUCAACG GGUAGGUAAA CGAA   NGI2ICR                       UUGGUUUACC UACCCGUUGA CUAAGUAAGC AAAC   NGI2R          
 
       [0052] or a variant sequence which differs from any of the preceding sequences  
       [0053] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0054] or changing within any of said sequences of one or more nucleotides,  
       [0055] or both,  
       [0056] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0057] A hybridization probe of the invention for detecting  Neisseria meningitidis  strains contains:  
       [0058] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                  Group NMI1:   GGTCAAGTGT GACGTCGCCC TG   NMI1                       CAGGGGGACG TCACACTTGA CC   NMI1IC                   CAGGGCGACG UCACACUUGA CC   NMI1ICR                   GGUCAAGUGU GACGUCGCCC UG   NMI1R               Group NMI2:   GTTCTTGGTC AAGTGTGACG TC   NMI2                   GACGTCACAC TTGACCAAGA AC   NMI2IC                   GACGUCACAC UUGACCAAGA AC   NMI2ICR                   GUUCUUGGUC AAGUGUGACG UC   NMI2R               Group NMI3:   GCGTICGTTA TAGCTATCTA CTGTGC   NMI3                   GCACAGTAGA TAGCTATAAC GAACGC   NMI3IC                   GCACAGUAGA UAGCUAUAAC GAACGC   NMI3ICR                   GCGUUCGUUA UAGCUAUCUA CUGUGC   NMI3R               Group NMI4:   TGCGTTCGAT ATTGCTATCT ACTGTGCA   NMI4                   TGCACAGTAG ATAGCAATAT CGAACGCA   NMI4IC                   UGCACAGUAG AUAGCAAUAU CGAACGCA   NMI4ICR                   UGCGUUCGAU AUUGCUAUCU ACUGUGCA   NMI4R               Group NMI5:   TTTTGTTCTTGGTCAAGTGTGACGTCGCCCTGAATGGATTCTGTTCCATT   NMI5                   AATGGAACAGAATCCATTCAGGGCGACGTCACACTTGACCAAGAACAAAA   NMI5IC                   AAUGGAACAGAAUCCAUUCAGGGCGACGUCACACUUGACCAAGAACAAAA   NMI5ICR                   UUUUGUUCUUGGUCAAGUGUGACGUCGCCCUGAAUGGAUUCUGUUCCAUU   NMI5R               Group NMI6   TTTGCCTAAC ATTCCGTTGA CTAGAACATC AGAC   NMI6                   GTCTGATGTT CTAGTCAACG GAATGTTAGG CAAA   NMI6IC                   GUCUGAUGUU CUAGUCAACG GAAUGUUAGG CAAA   NMI6ICR                   UUUGCCUAAC AUUCCGUUGA CUAGAACAUC AGAC   NMI6R          
 
       [0059] or a variant sequence which differs from any of the preceding sequences  
       [0060] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0061] or changing within any of said sequences of one or more nucleotides,  
       [0062] or both,  
       [0063] yet provided that in any of the above circumstances said probe still hybridiz s with the same RNA r DNA target as the corresponding unmodified sequence.  
       [0064] A hybridization probe of the invention for detecting  Branhamella catarrhalis  strains contains:  
       [0065] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group BCI1:                   TTAAACATCT TACCAAAG   BCI1                       CTTTGGTAAG ATGTTTAA   BCI1IC                       CUUUGGUAAG AUGUUUAA   BCI1ICR                       UUAAACAUCU UACCAAAG   BCI1R                       Group BCI2:           TTGATGTTTA AACTTGCTTG GTGGA   BCI2                       TCCACCAAGC AAGTTTAAAC ATCAA   BCI2IC                       UCCACCAAGC AAGUUUAAAC AUCAA   BCI2ICR                       UUGAUGUUUA AACUUGCUUG GUGGA   BCI2R          
 
       [0066] or a variant sequence which differs from any of the preceding sequences  
       [0067] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0068] or changing within any of said sequences of one or more nucleotides,  
       [0069] or both,  
       [0070] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0071] A hybridization probe of the invention for detecting  Haemophilus ducrevi  strains contains:  
       [0072] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to th maximum number of nucleotid s of th sel ct d nucleic acid,  
                                          Group HDI1:                   TTATTATGCG CGAGGCATAT TG   HDI1                       CAATATGCCT CGCGCATAAT AA   HDI1IC                       CAAUAUGCCU CGCGCAUAAU AA   HDI1ICR                       UUAUUAUGCG CGAGGCAUAU UG   HDI1R          
 
       [0073] or a variant sequence which differs from any of the preceding sequences  
       [0074] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0075] or changing within any of said sequences of one or more nucleotides,  
       [0076] or both,  
       [0077] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0078] A hybridization probe of the invention for detecting  Haemophilus influenzae  strains contains:  
       [0079] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group HII1:                   ACGCATCAAA TTGACCGCAC TT   HII1                       AAGTGCGGTC AATTTGATGC GT   HII1IC                       AAGUGCGGUC AAUUUGAUGC GU   HII1ICR                       ACGCAUCAAA UUGACCGCAC UU   HII1R                       Group HII2:           ACTTTGAAGT GAAAACTTAA AG   HII2                       CTTTAAGTTT TCACTTCAAA GT   HII2IC                       CUUUAAGUUU UCACUUCAAA GU   HII2ICR                       ACUUUGAAGU GAAAACUUAA AG   HII2R          
 
       [0080] or a variant sequenc which differs from any of the preceding sequences  
       [0081] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0082] or changing within any of said sequences of one or more nucleotides,  
       [0083] or both,  
       [0084] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0085] A hybridization probe of the invention for detecting  Bordetella pertussis  strains contains:  
       [0086] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group BPI1:                   CCACACCCAT CCTCTGGACA GGCTT   BPI1                       AAGCCTGTCC AGAGGATGGG TGTGG   BPI1IC                       AAGCCUGUCC AGAGGAUGGG UGUGG   BPI1ICR                       CCACACCCAU CCUCUGGACA GGCUU   BPI1R          
 
       [0087] or a variant sequence which differs from any of the preceding sequences  
       [0088] either by addition to or removal from any of their respective extremities of one r several nucleotides,  
       [0089] or changing within any of said sequences of one or more nucleotides,  
       [0090] or both,  
       [0091] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0092] A hybridizati n probe f the invention for detecting  Streptococcus pneumoniae  strains contains:  
       [0093] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group SPI1:                   GTGAGAGATC ACCAAGTAAT GCA   SPI1                       TGCATTACTT GGTGATCTCT CAC   SPI1IC                       UGCAUUACUU GGUGAUCUCU CAC   SPI1ICR                       GUGAGAGAUC ACCAAGUAAU GCA   SPI1R                       Group SPI2           AGGAACTGCG CATTGGTCTT   SPI2                       AAGACCAATG CGCAGTTCCT   SPI2IC                       AAGACCAAUG CGCAGUUCCU   SPI2ICR                       AGGAACUGCG CAUUGGUCUU   SPI2R                       Group SPI3           GAGTTTATGA CTGAAAGGTC AGAA   SPI3                       TTCTGACCTT TCAGTCATAA ACTC   SPI3IC                       UUCUGACCUU UCAGUCAUAA ACUC   SPI3ICR                       GAGUUUAUGA CUGAAAGGUC AGAA   SPI3R          
 
       [0094] or a variant sequence which differs from any of the preceding sequences  
       [0095] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0096] or changing within any of said sequences of one or more nucleotides,  
       [0097] or both,  
       [0098] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0099] A hybridization probe of the invention for detecting  Streptoc ccus agalactiae  strains contains:  
       [0100] either a sequence belonging to a nucleic acid selected from the following group of nucleic acids and which includes from 15 to the maximum number of nucleotides of the selected nucleic acid,  
                                          Group SAI1:                   AATCGAAAGG TTCAAATTGT T   SAI1                       AACAATTTGA ACCTTTCGAT T   SAI1IC                       AACAAUUUGA ACCUUUCGAU U   SAI1ICR                       AAUCGAAAGG UUCAAAUUGU U   SAI1R                       Group SAI2:           GGAAACCTGC CATTTGCGTC TT   SAI2                       AAGACGCAAA TGGCAGGTTT CC   SAI2IC                       AAGACGCAAA UGGCAGGUUU CC   SAI2ICR                       GGAAACCUGC CAUUUGCGUC UU   SAI2R                       Group SAI3:           TCCACGATCT AGAAATAGAT TGTAGAA   SAI3                       TTCTACAATC TATTTCTAGA TCGTGGA   SAI3IC                       UUCUACAAUC UAUUUCUAGA UCGUGGA   SAI3ICR                       UCCACGAUCU AGAAAUAGAU UGUAGAA   SAI3R                       Group SAI4:           TCTAGTTTTA AAGAAACTAG GTT   SAI4                       AACCTAGTTT CTTTAAAACT AGA   SAI4IC                       AACCUAGUUU CUUUAAAACU AGA   SAI4ICR                       UCUAGUUUUA AAGAAACUAG GUU   SAI4R          
 
       [0101] or a variant sequence which differs from any of the preceding sequences  
       [0102] either by addition to or removal from any of their respective extremities of one or several nucleotides,  
       [0103] or changing within any of said sequences of one or more nucleotides,  
       [0104] or both,  
       [0105] yet provided that in any of the above circumstances said probe still hybridizes with the same RNA or DNA target as the corresponding unmodified sequence.  
       [0106] The invention also relates to hybridization probes for detecting  Campylobacter jejuni  and  Campylobacter coli  strains containing a sequence from 15 to the maximum number of nucleotides derived from the 16S-23S rRNA spacer sequence shown in FIG. 10, or the corresponding one wherein T is replaced by U, or its complement, or the corresponding one wherein T is raplced by U, provided that the probes, at the appropriate conditions, hybridize specifically with DNA and/or RNA from  Campylobacter jejuni  and  Campylobacter coli.    
       [0107] In the sequences given in groups NGI1, NGI2, NMI1, NMI2, NMI3, NMI4, NMI5, NMI6, BCI1, BCI2, HDI1, HII1, HII2, BPI1, SPI1, SPI2, SPI3, SAI1, SAI2, SAI3, and SAI4 the letters stand for the following nucleotides:  
       [0108] A: Adenylic residue  
       [0109] C: Cytidylic residue  
       [0110] G: Guanidylic residue  
       [0111] T: Thyidylic residue  
       [0112] U: Uracylic residue  
       [0113] Under the expression “target” is meant a sequence complementary to any of the sequences of groups NGI1, NGI2, NKI1, NMI2, NMI3, NMI4, NMI5, NMI6, BCI1, BCI2, HDI1, HII1, HII2, BPI1, SPI1, SPI2, SPI3, SAI1, SAI2, SAI3, and SAI4 as previously defined herein.  
       [0114] In cases where the probe of the invention would comprise nucleic acid elongations on either side or both of said above defined sequences—e.g. nucleic acid fragments of cloning vector or linker fragments resulting from the cleavage of said pr be out of said cloning vector—it is understood that such elongations sh uld be selected such as to av id the possibility that they could themselves hybridize with any other corresponding complementary nucleic acid sequence outside of the above target in a DNA of any micro-organism likely to be tested by the process of this invention as later defined. Such hybridization would be of a parasitical nature and reduce the specificity of the probe. Preferred probes consist of nucleic acid fragments formed from any of the sequences of the groups defined above, with said fragments containing from 15 to the maximum number of nucleotides of the relevant nucleic acid sequence.  
       [0115] It is understood that in the above nucleotide sequences (and in the other ones referred to hereafter), the left end of the formulae always corresponds to a 5′ extremity and the right end to a 3′ extremity of the sequence concerned.  
       [0116] When reference is further made therein to a “probe of group ‘X’”—with ‘X’ from NGI1, NGI2, NMI1, NMI2, NMI3, NMI4, NMI5, NMI6, BCI1, BCI2, HDI1, HII1, HII2, BPI1, SPI1, SPI2, SPI3, SAI1, SAI2, SAI3, and SAi4—it should be understood that such probe has a sequence included in one of the nucleic acids belonging to that group as defined above or further defined hereafter.  
       [0117] It is also understood that the word “nucleotide” as used herein refers indistinctly to ribonucleotides and deoxyribonucleotides and modified nucleotides such as inosine unless otherwise specified. The expression “nucleotides” also encompasses those which further comprise modification groups, e.g. chemical modification groups which do not affect their hybridization capabilities fundamentally. Such modification groups aim, for instance, at facilitating their coupling, either directly or indirectly, with suitable markers or labels for the subsequent detection of the probes so marked or labeled particularly in their hybridization products with the relevant RNA or DNA strand, e.g. that or those initially contained in a biological sample together with other DNA(s) and/or RNA(s).  
       [0118] For instance, such modification groups are recognizable by antibodies which, in turn, can be recognized specifically by other antibodies, carrying a suitable enzymatic or fluorescent or chemiluminescent label. Possible labeling procedures will further be exemplified later herein.  
       [0119] The invention also relates to probes having any of the sequences defined above and in which some nucleotides are different, provided that the different nucleotide(s) do(es) not alter the specificity of the probes defined above. Some probes may consist of one of the nucleic acids belonging to any of the groups which are set forth above or of part thereof, with said probes however including nucleotidic elongation on either sides thereof to the extent that such elongations do not alter the specificity of said probes with the genetic material of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  strains.  
       [0120] The invention thus provides for probes which are either replicas (those designated by numbers followed by “IC” or “ICR”) in terms of nucleotide sequence of sequences contained in the RNAs or DNAs of most  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptoc ccus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  with occasionally a few insignificant differences in nucleotid sequences or f rmed of sequ nces, those designated by bare numbers or by numbers followed by “R”, complementary to sequences included in the natural DNAs or RNAs of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus Pneumoniae , or  Campylobacter jejuni  and  Camplobacter coli.    
       [0121] More particularly, it should be noted that the target sequences in the DNAs concerned consist in any of the following successive sequences present in most, if not all,  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumonia , or  Campylobacter jejuni  and  Campylobacter coli  strains, subject to possible insignificant natural differences from one strain to another, whereby such natural differences are not likely to affect the hybridization specificity of the probes of this invention with such targets:  
       [0122] In the case of  Neisseria gonorrhoeae  
                                      GCGAAGTAGA ATAACGACGC ATCG                           GTTTGCTTAC TTAGTCAACG GGTAGGTAAA CGAA          
 
       [0123] In the case of  Neisseria meningitidis  
                          CAGGGCGACG TCACACTTGA CC                   GACGTCACAC TTGACCAAGA AC               GCACAGTAGA TAGCTATAAC GAACGC               TGCACAGTAG ATAGCAATAT CGAACGCA               AATGGAACAGAATCCATTCAGGGCGACGTCACACTTGACCAGAACAAAA               GTCTGATGTT CTAGTCAACG GAATGTTAGG CAAA          
 
       [0124] In the case of  Branhamella catarrhalis  
                                      CTTTGGTAAG ATGTTTAA                           TCCACCAAGC AAGTTTAAAC ATCAA          
 
       [0125] In the case of  Haemophilus ducreyi  
                          CAATATGCCT CGCGCATAAT AA              
 
       [0126] In the case of  Bordetella pertussis  
                                      AAGCCTGTCC AGAGGATGGG TGTGG              
 
       [0127] In the case of  Haemophilus influenzae  
                                      AAGTGCGGTC AATTTGATGC GT                           CTTTAAGTTT TCACTTCAAA GT          
 
       [0128] In the case of  Streptococcus pneumoniae  
                                      TGCATTACTT GGTGATCTCT CAC                           AAGACCAATG CGCAGTTCCT                       TTCTGACCTT TCAGTCATAA ACTC          
 
       [0129] In the case of  Streptococcus agalactiae  
                                      AACAATTTGA ACCTTTCGAT T                           AAGACGCAAA TGGCAGGTTT CC                       TTCTACAATC TATTTCTAGA TCGTGGA                       AACCTAGTTT CTTTAAAACT AGA          
 
       [0130] The probes according to the invention can be formed by cloning of recombinant plasmids containing inserts including the corresponding nucleotide sequences, if need be by cleaving the latter out from the cloned plasmids upon using the adequate nucleases and recovering them, e.g. by fractionation according to molecular weight. The probes according to the invention can also be synthesized chemically, for instance by the conventional phospho-triester method.  
       [0131] The invention also relates to a process for detecting  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  strains in a biological sample, wherein said process comprises contacting said biological sample in which the nucleic acids (DNAs and RNAs) have been made accessible to hybridization, if need be under suitable denaturation conditions, with a probe of the invention under conditions enabling hybridization b tween the probe and complementary nucleic acids of the strains, which may be present in the sample, and detecting the hybrids possibly formed.  
       [0132] The process of the invention enables to discriminate  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Strentococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  from most other organism such as yeast, fungi, protozoa, other bacterial strains, and/or human cells which are liable to the be present in the sample in which the organisms of interest are sought. The process relates to the detection of  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , r  Campylobacter jejuni  and  Campylobacter coli  strains being directly in the sample or after the strain has been cultured.  
       [0133] The detection of a hybrid can be interpreted as meaning that an infection due to  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae , and  Streptococcus pneumoniae  was present in the biological sample, when any of the probes of groups NGI1, NGI2, NMI1, NMI2, NMI3, NMI4, NMI5, NMI6, BCI1, BCI2, HDI1, HII1, HII2, BPI1, SPI1, SPI2, SPI3, SAI1, SAI2, SAI3, and SAI4 is being used, respectively.  
       [0134] According to an advantageous embodiment of the invention, in the process for detecting  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haem philus ducrevi, Haem philus influenzae, Bordetella pertussis, Strept coccus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  strains, the probes used are the ones hybridizing both with DNA globally and RNA of the  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  strains, which may be present in the biological sample.  
       [0135] The hybridization conditions can be monitored relying upon several parameters, e.g. hybridizati n temperature, the nature and concentration of the components of the media, and the temperature under which the hybrids formed are washed.  
       [0136] The hybridization and wash temperature is limited in upper value, according to the probe (its nucleic acid composition, kind and length) and the maximum hybridization or wash temperature of the probes described herein is about 30° C. to 58° C. At higher temperatures duplexing competes with the dissociation (or denaturation) of the hybrid formed between the probe and the target.  
       [0137] A preferred hybridization medium contains about 3×SSC (1×SSC=0.15 M NaCl, 0.015 M sodium citrate, pH 7.0), about 25 mM of phosphate buffer pH 7.1, and 20% deionized formamide, 0.02% Ficoll, 0-0.02% bovine serum albumin, 0.02% polyvinylpyrrolidone and about 0.1 mg/ml sheared denatured salmon sperm DNA.  
       [0138] A preferred wash medium contains about 3×SSC, 25 mM phosphate buffer pH 7.1 and 20% deionized formamide. Other hybridization or wash media can be used as well.  
       [0139] However, when modifications are introduced, be it either in the probes or in the media, the temperatures at which the probes can be used to obtain the required specificity should be changed according to known relationships, such as those described in the following reference: B. D. HAMES and S. J. HIGGINS, (eds.). Nucleic acid hybridization. A practical approach, IRL Press, Oxford, U.K., 1985.  
       [0140] In this respect it should also be noted that, in general, DNA:DNA hybrids are less stable then RNA:DNA or RNA:RNA hybrids. Depending on the nature of the hybrid to be detected, the hybridization conditions should be adapted accordingly to achieve specific detection.  
       [0141] The process for detecting  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducreyi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Campylobacter coli  strains generally, according to the invention can be carried out by suitably adjusting the hybridization temperature to a value at which hybridization is specific. In such a case, washing under more stringent conditions is not necessary.  
       [0142] According to another embodiment of the process of the invention, the hybridization temperature need not necessarily be adjusted to the value at which hybridization is specific and, in particular, can be lower than the temperature at which hybridization is specific, provided washing is carried out at a temperature corresponding to the value at which hybridization is specific.  
       [0143] In a process embodiment for detecting  Neisseria gonorrhoeae  strains (and for distinguishing them from other bacterial taxa) with a probe of group NGI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 50° C., the media being those defined above.  
       [0144] In a process embodiment for detecting  Neisseria gonorrhoeae  strains (and for distinguishing them from other bacterial taxa) with a probe of group NGI2, the hybridization temperature and/or the wash temperature is suitably adjusted t about 50° C., the media being those defined above.  
       [0145] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0146] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI2, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0147] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI3, the hybridization temperature and/or the wash temperature is suitably adjusted to about 40° C., the media being those defined above.  
       [0148] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI4, the hybridization temperature and/or the wash temperature is suitably adjusted to about 48° C., the media being those defined above.  
       [0149] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI5, the hybridization temperature and/or the wash temperature is suitably adjusted to about 58° C., the media being those defined above.  
       [0150] In a process embodiment for detecting  Neisseria meningitidis  strains (and for distinguishing them from other bacterial taxa) with a probe of group NMI6, the hybridization temperature and/or the wash temperature is suitably adjusted to about 50° C., th media being those defined above.  
       [0151] In a process embodiment for detecting  Branhamella catarrhalis  strains (and for distinguishing them from other bacterial taxa) with a probe of group BCI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 30° C., the media being those defined above.  
       [0152] In a process embodiment for detecting  Branhamella catarrhalis  strains (and for distinguishing them from other bacterial taxa) with a probe of group BCI2, the hybridization temperature and/or the wash temperature is suitably adjusted to about 42° C., the media being those defined above.  
       [0153] In a process embodiment for detecting  Bordetella pertussis  strains (and for distinguishing them from other bacterial taxa) with a probe of group BPI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 55° C., the media being those defined above.  
       [0154] In a process embodiment for detecting  Haemophilus ducreyi  strains (and for distinguishing them from other bacterial taxa) with a probe of group HDI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 40° C., the media being those defined above.  
       [0155] In a process embodiment for detecting  Haemophilus influenzae  strains (and for distinguishing them from other bacterial taxa) with a probe of group HII1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 55° C., the media being those defined above.  
       [0156] In a pr cess embodiment for detecting  Haemophilus influenzae  strains (and for distinguishing them from other bacterial taxa) with a probe f group HI12, the hybridization temperature and/or the wash temperature is suitably adjusted to about 35° C., the media being those defined above.  
       [0157] In a process embodiment for detecting  Streptococcus agalactiae  strains (and f r distinguishing them from other bacterial taxa) with a probe of group SAI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 35° C., the media being those defined above.  
       [0158] In a process embodiment for detecting  Streptococcus agalactiae  strains (and for distinguishing them from other bacterial taxa) with a probe of group SAI2, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0159] In a process embodiment for detecting  Streptococcus agalactiae  strains (and for distinguishing them from other bacterial taxa) with a probe of group SAI3, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0160] In a process embodiment for detecting  Streptococcus agalactiae  strains (and for distinguishing them from other bacterial taxa) with a probe of group SAI4, the hybridization temperature and/or the wash temperature is suitably adjusted to about 37° C., the media being those defined above.  
       [0161] In a process embodiment for detecting  Streptococcus pneumoniae  strains (and for distinguishing them from other bacterial taxa) with a probe of group SPI1, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0162] In a pr cess embodiment f r detecting  Streptococcus pneumoniae  strains (and for distinguishing them from other bacterial taxa) with a probe f group SPI2, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0163] In a process embodiment for detecting  Streptococcus pneumoniae  strains (and for distinguishing them from other bacterial taxa) with a probe of group SPI3, the hybridization temperature and/or the wash temperature is suitably adjusted to about 45° C., the media being those defined above.  
       [0164] The invention further relates to a kit for detecting specifically  Neisseria meningitidis  strains containing:  
       [0165] a probe specific for  Neisseria meningitidis  i.e. a probe of group NMI1, NMI2, NMI3, NMI4, NMI5 or NMI6;  
       [0166] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Neisseria meningitidis  to be carried out,  
       [0167] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0168] The invention further relates to a kit for detecting specifically  Neisseria gonorrhoeae  strains containing:  
       [0169] a probe specific for  Neisseria gonorrhoeae  i.e. a probe of group NGI1 or NGI2;  
       [0170] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Neisseria gonorrhoeae  to be carried out,  
       [0171] the means for detecting the hybrids resulting from the proceeding hybridizati n, when appropriate.  
       [0172] The invention further relates to a kit for d tecting specifically  Branhamella catarrhalis  strains containing:  
       [0173] at least one probe selected among any of those that are specific for  Branhamella catarrhalis  as above defined, i.e. a probe of group BCI1 or BCI2;  
       [0174] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAS and/or RNAs of a strain of  Branhamella catarrhalis  to be carried out,  
       [0175] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0176] The invention further relates to a kit for detecting specifically  Haemophilus ducreyi  strains containing:  
       [0177] at least one probe selected among any of those that are specific for  Haemophilus ducreyi  as above defined, i.e. a probe of group EDI1;  
       [0178] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Haemophilus ducreyi  to be carri d out,  
       [0179] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0180] The invention further relates to a kit for detecting specifically  Bordetella pertussis  strains containing:  
       [0181] at least one probe selected among any of those that are specific for  Bordetella pertussis  as above defined, i.e. a probe of group BPI1;  
       [0182] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and nly the DNAs and/or RNAs of a strain of  Bordetella pertussis  to be carried out,  
       [0183] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0184] The invention further relates to a kit for detecting specifically  Haemophilus influenzae  strains containing:  
       [0185] at least one probe selected among any of those that are specific for  Haemophilus influenzae  as above defined, i.e. a probe of group HII1 or HII2;  
       [0186] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Haemophilus influenzae  to be carried out,  
       [0187] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0188] The invention further relates to a kit for detecting specifically  Streptococcus agalactiae  strains containing:  
       [0189] at least one probe selected among any of those that are specific for  Streptococcus agalactiae  as above defined, i.e. a probe of group SAI1, SAI2, SAI3, or SAI4;  
       [0190] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Streptococcus agalactiae  to be carried out,  
       [0191] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0192] The invention further relates to a kit for detecting specifically  Streptococcus pneumoniae  strains containing:  
       [0193] at least ne probe selected among any of those that are specific for  Streptoc ccus pneumoniae  as above defined, i.e. a probe of group SPI1, SPI2 or SPI3;  
       [0194] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Streptococcus pneumoniae  to be carried out,  
       [0195] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0196] The invention further relates to a kit for detecting specifically  Campylobacter jejuni  and  Campylobacter coli  strains containing:  
       [0197] at least one probe selected among any of those that are specific for  Campylobacter jejuni  and  Campylobacter coli  as above defined;  
       [0198] the buffer or components necessary for producing the buffer enabling an hybridization reaction between these probes and only the DNAs and/or RNAs of a strain of  Campylobacter jejuni  and  Campylobacter coli  to be carried out,  
       [0199] the means for detecting the hybrids resulting from the proceeding hybridization, when appropriate.  
       [0200] The probes of the invention can be used in a sandwich hybridization system which enhances the specificity of a nucleic acid probe-based assay. The principle and the use of sandwich hybridizations in a nucleic acid probe-based assay have been already described (e.g.: DUNN and HASSEL, Cell, 12: 23-36; 1977; RANKI et al., Gene, 21: 77-85; 1983). Although direct hybridization assays have favorable kinetics, sandwich hybridizations are advantageous with respect to a higher signal-to-noise ratio. Moreover, sandwich hybridizations can enhance the specificity of a nucleic acid probe based assay.  
       [0201] If properly designed, a sandwich hybridization assay indeed maximizes the specificity of a nucleic acid probe-based test when using two probes recognizing two different nucleic acid str tches of one and the same organism. The only demands which must be met are that both probes (i) hybridize to the same nucleic acid molecule of the target organism and (ii) do not hybridize to the same non-target organisms.  
       [0202] For two given probes I and II the sandwich hybridization system can be described as follows:  
       [0203] Probe n o  I hybridizes to nucleic acid from organisms A and B (not with C);  
       [0204] Probe n o  II hybridizes to nucleic acid from organisms A and C (not with B).  
       [0205] Since it is absolutely required that both probes hybridize to the target nucleic acid, a detectable signal will be generated only if the nucleic acid from organism A is present in the sample. It is obvious that if one of the probes is specific for the organism to be detected, the other probe can be composed of any specific or non-specific sequence provided that it hybridizes to the same target molecule than the first probe.  
       [0206] The probes of the invention can be used in a sandwich hybridization assay which is specific for  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemonhilus ducrevi, Haemophilus influenzae, Bordetella pertussis, Streptococcus agalactiae, Streptococcus pneumoniae , or  Campylobacter jejuni  and  Capylobacter coli  respectively in combination with another, non-specific or specific, probe hybridizing to the same target molecule. In the sandwich hybridization process, the probes can be added simultaneously or not, to the biological sample in which the target DNA or RNA is sought.  
       [0207] The invention also relates t a kit for sandwich hybridization assay, for the detection in vitro of  Neisseria gonorrhoeae  strains in a biological sample, with said kit containing:  
       [0208] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Neisseria gonorrhoeae,    
       [0209] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAS of a strain of  Neisseria gonorrhoeae  to be carried out,  
       [0210] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0211] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro f Neisseria meningitidis strains in a biological sample, with said kit containing:  
       [0212] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Neisseria meningitidis,    
       [0213] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Neisseria meningitidis  to be carried out,  
       [0214] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0215] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Branhamella catarrhalis  strains in a biological sample, with said kit containing:  
       [0216] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Branhamella catarrhalis,    
       [0217] the buffer or components necessary for producing the buffer enabling-hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Branhamella catarrhalis  to be carried ut,  
       [0218] the means for detecting the hybrids resulting from the prec ding hybridization, when appropriate.  
       [0219] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Haemophilus ducreyi  strains in a biological sample, with said kit containing:  
       [0220] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Haemophilus ducreyi,    
       [0221] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Haemophilus ducreyi  to be carried out,  
       [0222] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0223] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Haemophilus influenzae  strains in a biological sample, with said kit containing:  
       [0224] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Haemophilus influenzae,    
       [0225] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Haemophilus influenzae  to be carried out,  
       [0226] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0227] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Bordetella pertussis  strains in a biological sample, with said kit containing:  
       [0228] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Bordetella pertussis,    
       [0229] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Bordetella pertussis  to be carried out,  
       [0230] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0231] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Streptococcus agalactiae  strains in a biological sample, with said kit containing:  
       [0232] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Streptococcus agalactiae,    
       [0233] the buffer or components necessary for producing the-buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Streptococcus agalactiae  to be carried out,  
       [0234] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0235] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Streptococcus pneumoniae  strains in a biological sample, with said kit containing:  
       [0236] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Streptococcus pneumoniae,    
       [0237] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Streptococcus pneumoniae  to be carried out,  
       [0238] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0239] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro of  Campylobacter jejuni  strains in a bi logical sample, with said kit containing:  
       [0240] at least two probes targeting the same nucleic acid molecul and f which at least one is specific for  Campylobacter jejuni,    
       [0241] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Campylobacter jejuni  to be carried out,  
       [0242] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0243] The invention also relates to a kit for sandwich hybridization assay, for the detection in vitro f  Campylobacter coli  strains in a biological sample, with said kit containing:  
       [0244] at least two probes targeting the same nucleic acid molecule and of which at least one is specific for  Campylobacter coli,    
       [0245] the buffer or components necessary for producing the buffer enabling hybridization reaction between these probes and the DNAs and/or RNAs of a strain of  Campylobacter coli  to be carried out,  
       [0246] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0247] The probes of the invention can be used also in a competition hybridization protocol.  
       [0248] In a competition hybridization, the target molecule competes with the hybrid formation between a specific probe and its complement. The more target is present, the lower the amount of-hybrid formed between the probe and its complement. A positive signal, which indicates that the specific target was present, is seen by a decrease in hybridization reaction as compared with a system to which no target was added. In a particular embodiment, the specific oligonucleotide probe, conveniently labeled, is hybridized with the target molecule. Next, the mixture is transferred to a recipient (e.g. a micr titer dish vell) in which a oligonucleotide complementary to the specific probe is fixed and the hybridization is continued. After washing, the hybrids between the complementary oligonucleotide and the probe are measured, preferably quantitatively, according to the label used.  
       [0249] The oligonucleotides of the invention can be used either as amplification primers in the polymerase chain reaction technique (PCR; Mullis and Faloona, Methods in Enzymology 155:335-350, 1987) to generate specific enzymatically amplified fragments and/or as probes to detect fragments amplified between bracketing oligonucleotide primers.  
       [0250] The specificity of a PCR-assisted hybridization assay can be controlled at different levels.  
       [0251] The amplification process or the detection process or both can be specific. The latter case, giving the highest specificity, is preferred. Such a highly specific PCR-assisted test can be developed using the probes of the invention.  
       [0252] However, in some occurrences, a non-specific amplification process, using conserved primers bracketing the detection probes of the invention, coupled to a specific detection, might be advantageous in order to standardize the amplification process in such a way that it can be used for a great variety of organisms.  
       [0253] Amplification primers to be used in a standardized amplification process can be found in the conserved region of the 16S and 23S rRNA gene flanking the spacer region (see Example 1).  
       [0254] The invention also relates to a process for the in vitro detection of one microorganism or to the simultaneous in vitro detection of several microorganisms contained in a biological sample using any of the probes of the invention and specific for the microorganism(s) t be detected, wherein the DNA and/or RNA present in the biological sample (and comprising the target s quenc) is labeled, preferably using enzymatic amplificati n with at least one set of primers flanking the probe region, and wherein said biological sample is contacted with a membrane on which one or more oligonucleotide probes are dot spotted on a known location, in a medium enabling specific hybridization of the amplified target sequence and the probes on the membrane and wherein the hybrids resulting from the hybridizations are detected by appropriate means.  
       [0255] When amplification is necessary, its aim is to amplify the target sequence (whereby the amplification of the flanking regions of the target sequence also occurs) and to label only the amplified regions.  
       [0256] When there is enough target sequence in the biological sample, amplification is not needed.  
       [0257] In such a case, labeling has to be carried out, for instance, either chemically or by addition of specific dyes, prior to hybridization and it is to be noted that all the DNA and/or RNA present in the biological sample is labeled.  
       [0258] The invention also relates to a kit for the in vitro detection of one microorganism or for the simultaneous in vitro detection of several microorganisms contained in a biological sample, with said-kit containing:  
       [0259] at least one of the probes according to the invention and specific for the microorganism(s) to be detected, which is dot spotted to a membrane,  
       [0260] the primers needed for performing enzymatic amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0261] the buffers or components necessary for producing the buffers enabling enzymatic amplification and/r enabling a hybridization reaction between th se pr bes and the DNAs and/or RNAs of a microorganism or microorganisms which are to be detected to to be carried out,  
       [0262] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0263] The above-mentioned process and kit involve the reversed hybridization dot-blot assay, such as the reversed dot-blot assay described by Saiki et al. (Proc. Natl. Acad. Sci. USA, 86:6230-6234, 1989).  
       [0264] In this case, the target sequences can first be enzymatically amplified using PCR with 5′ biotinylated primers. In a second step, the amplified products are detected upon hybridization with specific oligonucleotides immobilized on a solid support. Several modifications of this technique can be envisaged such as the one described in Example 2. For example, this technique may be particularly advantageous for the simultaneous and specific detection of a variety of microorganisms which may be present in a particular clinical sample after PCR with universal primers flanking the spacer region and hybridization with a membrane on which different specific oligonucleotide probes for the organisms of interest are dot-spotted. Some examples of advantageous panels of specific oligonucleotide probes which can be used in a reversed hybridization assay as described above are:  
       [0265] (i) sputum-panel:  Moraxella  ( Branhamella )  catarrhalis    
       [0266] Streptococcus pneumoniae    
       [0267] Haemophilus influenzae    
       [0268] (ii) CSF-panel:  Neisseria meningitidis    
       [0269] Haemophilus influenzae    
       [0270] Streptoc ccus pneumoniae  
       [0271] (iii) Urogenital-panel:  Neisseria gon rrhoeae    
       [0272] Haemophilus ducreyi  
       [0273] Chlamydia trach matis  
       [0274] Treponema pallidum  
       [0275] Evidently these panels can be extended by adding probes for other clinically relevant micro-organisms. Also panels for other clinical samples, such as samples coming from peridontal pockets or blood samples, may be of interest.  
       [0276] For the PCR also nonuniversally conserved primers, for instance primers located in the spacer region itself, can be used and the PCR can be performed either with one set of primers or with different sets of primers in the same reaction vessel.  
       [0277] Reversed hybridization may also be carried out without an amplification step. In that particular case, the nucleic acids present in the sample have to be labeled or modified, specifically or not, for instance, chemically or by addition of specific dyes, prior to hybridization.  
       [0278] In most cases, the number of specific probes for the organisms of interest which can be derived from the spacer regions is not limited to the probes described in this text.  
       [0279] For some organisms only one or two probes are described to demonstrate the feasibility of spacer regions for the development of highly specific and sensitive probes for a variety of bacteria. The only exception is  Bordetella pertussis  for which only one particular region (from nucleotide 271 to 299 in the  Bordetella pertussis  sequence; FIG. 2, top line) of the spacer region has a specific sequence. However, from the spacer region sequence of  Bordetella pertussis , probes may be devised which can be valuable in the simultaneous detection of highly related Bordetella species. Pr bes which det ct Bordetella species other than  Bordetella pertussis  may also be deduced from the sequences discl sed in FIG. 2. Likewise, potentially specific probes f r  Moraxella nonliquefaciens  and  Haemophilus influenzae  biogroup aegyptius may be inferred from the spacer region sequence shown in FIGS. 7 and 8, respectively.  
       [0280] The invention also relates to a kit for the in vitro detection of one ore more  Neisseria gonorrhoeae  strains in a biological sample, with said kit containing:  
       [0281] at least one probe selected among any of those according to the invention and specific for  Neisseria gonorrhoeae , which is fixed to a solid support,  
       [0282] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0283] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of Neisseria gonorrhoeae to be carried out,  
       [0284] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0285] The invention also relates to a kit for the in vitro-detection of one ore more  Neisseria meningitidis  strains in a biological sample, with said kit containing:  
       [0286] at least one probe selected among any of those according to the invention and specific for  Neisseria meningitidis , which is fixed to a solid support,  
       [0287] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing th target sequence of the above-mentioned probe, when appropriate,  
       [0288] the buffers or components necessary for producing the buffers enabling enzyzatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of  Neisseria meningitidis  to be carried out,  
       [0289] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0290] The invention also relates to a kit for the in vitro detection of one ore more  Haemophilus ducreyi  strains in a biological sample, with said kit containing:  
       [0291] at least one probe selected among any of those according to the invention and specific for  Haemophilus ducreyi , which is fixed to a solid support,  
       [0292] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0293] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of  Haemophilus ducreyi  to be carried out,  
       [0294] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0295] The invention also relates to a kit for the in vitro detection of one ore more  Branhamella catarrhalis  strains in a biological sample, with said kit containing:  
       [0296] at least one probe selected among any of those according to the invention and specific for  Branhamella catarrhalis , which is fixed to a solid support,  
       [0297] the primers needed for perf rming enzymatical amplification of the DNA and/r RNA containing the targ t sequence of the above-mentioned probe, when appr priate,  
       [0298] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or ENAs of a strain of  Branhamella catarrhalis  to be carried out,  
       [0299] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0300] The invention also relates to a kit for the in vitro detection of one ore more  Bordetella pertussis  strains in a biological sample, with said kit containing:  
       [0301] at least one probe selected among any of those according to the invention and specific for  Bordetella pertussis , which is fixed to a solid support,  
       [0302] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0303] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain f  Bordetella pertussis  to be carried out,  
       [0304] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0305] The invention also relates to a kit for the in vitro detection of one ore more  Haemophilus influenzae  strains in a biological sample, with said kit containing:  
       [0306] at least one probe selected among any of those according to the invention and specific for  Haemophilus influenzae , which is fixed t a solid support,  
       [0307] the primers need d for p rforming enzymatical amplification f th DNA and/r RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0308] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of  Haemophilus influenzae  to be carried out,  
       [0309] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0310] The invention also relates to a kit for the in vitro detection of one ore more  Streptococcus pneumoniae  strains in a biological sample, with said kit containing:  
       [0311] at least one probe selected among any of those according to the invention and specific for  Streptococcus pneumoniae , which is fixed to a solid support,  
       [0312] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0313] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of  Streptococcus pneumoniae  to be carried out,  
       [0314] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0315] The invention also relates to a kit for the in vitro detection of one ore more  Streptococcus agalactiae  strains in a biological sample, with said kit containing:  
       [0316] at least ne probe selected among any of those according t the invention and specific for  Streptococcus agalactiae , which is fixed to a solid support,  
       [0317] the primers needed for perf rming enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probe, when appropriate,  
       [0318] the buffers or components necessary for producing the buffers enabling enzymatical amplification and/or enabling hybridization reaction between said probe and the DNAs and/or RNAs of a strain of  Streptococcus agalactiae  to be carried out,  
       [0319] the means for detecting the hybrids resulting from the preceding hybridization, when appropriate.  
       [0320] The invention also relates to a kit for the in vitro detection of one ore more  Campylobacter jejuni  and  Campylobacter coli  strains in a biological sample, with said kit containing:  
       [0321] at least one probe selected among any of those according to the invention and specific for  Campylobacter jejuni , and at least one pr b selected among any of those according to the invention and specific for  Campylobacter coli , which is fixed to a solid support,  
       [0322] the primers needed for performing enzymatical amplification of the DNA and/or RNA containing the target sequence of the above-mentioned probes, when appropriate,  
       [0323] the buffers or components necessary for producing the buffers enabling enzymatical amplificati n and/or enabling hybridization reaction between said probes and the DNAs and/or RNAs of a strain of  Campylobacter jejuni  and  Campylobacter coli  to be carried out,  
       [0324] the means for detecting the hybrids resulting fr m th preceding hybridization, when appropriate.  
       [0325] Conditions for the Use of Probes:  
       [0326] The pr bes of the invention are advantageously labeled. Any conventional label can be used. The probes can be labeled by means of radioactive tracers such as  32 P,  35 S,  125 I,  3 H and  14 C.  
       [0327] The radioactive labeling can be carried out according to any conventional method such as terminal labeling at the 3′ or 5′ position with the use of a radiolabeled nucleotide, a polynucleotide kinase (with or without dephosphorylation by a phosphatase), a terminal transferase, or a ligase (according to the extremity to be labeled). One of the probes of the invention can be the matrix for the synthesis of a chain consisting of several radioactive nucleotides or of several radioactive and nonradioactive nucleotides.  
       [0328] The probes of the invention can also be prepared by chemical synthesis using one or several radioactive nucleotides. Another method for radioactive labeling is a chemical iodination of the probes of the inventi n which leads to the binding of several  125 I atoms on the probes.  
       [0329] If one of the probes of the invention is made radioactive to be used for hybridization with a nonradioactive RNA or DNA, the method of detecting hybridization will depend on the radioactive tracer used. Generally, autoradiography, liquid scintillation, gamma counting or any other conventional method enabling one to detect an ionizing ray issued by the radioactive tracer can be used.  
       [0330] Nonradioactive labeling can also be used by associating the probes of the invention with residues having: immunological properties (e.g. antigen or hapten), a specific affinity for some reagents (e.g. ligand), properties providing a detectable enzymatic reacti n (e.g. enzyme, co-enzyme, enzyme substrate or substrate taking part in an enzymatic reacti n), or physical pr perties such as fluorescence, emission r absorption of light at any wavelength. Antibodies which specifically detect the hybrids formed by the probe and the target can also b used.  
       [0331] A nonradioactive label can be provided when chemically synthesizing a probe of the invention, the adenosine, guanosine, cytidine, thymidine and uracyl residues thereof being liable to be coupled to other chemical residues enabling the detection of the probe or the hybrids formed between the probe and a complementary DNA or RNA fragment.  
       [0332] However, the nucleotidic sequence of the probe, when modified by coupling one or more nucleotides to other chemical residues, would be the same as the nucleotide sequence of one of the probes of the invention.  
       [0333] The invention also relates to processes for detecting RNA end/or DNA with the probes of the invention by hybridization, which have been labeled and can be detected as described above. In this regard, conventional methods of hybridization can be used.  
       [0334] For detecting cells derived from or themselves being living organisms, the RNA and/or DNA of these cells, if need be, is made accessible by partial or total lysis of the cells using chemical or physical processes, and contacted with one or several probes of the invention which can be detected. This contact can be carried out on an appropriate support such as a nitrocellulose, cellulose, or nylon filter in a liquid medium or in solution. This contact can take place under suboptimal, optimal conditions, or under restrictive conditions (i.e. conditions enabling hybrid formation only if the sequences are perfectly homologous on a length of molecule). Such conditions include temperature, concentration of reactants, the presence of substances lowering the optimal temperature of pairing of nucleic acids (e.g. formamide, dimethylsulfoxide and ur a) and the presenc of substances apparently lowering the reaction volume and/or accelerating hybrid formation (e.g. dextran sulfate, polyethyleneglycol or phenol).  
       [0335] The elimination of a probe of the invention which has not hybridized can be carried out by washing with a buffer solution of appropriate ionic strength and at an appropriate temperature with or without treatment with S1 nuclease or any other enzyme digesting single-strand DNA or RNA but not digesting DNA-RNA hybrids or double-strand DNA.  
       [0336] In a liquid medium, the hybrids of the probe of the invention paired to the cellular DNA or RNA fragments can be separated from the rest of the liquid medium in different ways, e.g. by chromatography over hydroxyapatite.  
       [0337] Then the hybridized probes are detected by means of the label on the probe.  
       [0338] In order to target the chromosomal DNA fragments, after treating RNA by one or several enzymes and denaturation of DNA fragments (i.e. separation of both chains), one of the probes of the invention is contacted with the DNA fragments under the conditions enabling hybridization, and after the time necessary to reach the end of the hybridization, the non-hybridized fragments are separated from the hybridized fragments and the label is detected as described above for the detection of the cells.  
       [0339] Generally speaking, the different probes of the invention can also be contained in recombinant DNA enabling their cloning, if the presence of a heterologous DNA is not a nuisance for the specificity of the probes in the enc mpassed uses.  
       [0340] In FIGS.  1  to  10 , alignments of spacer regi ns (completely or partially sequenced) found in various micr organisms are shown as examples. Matches and gaps are indicated by “:” and “−”, respectively. For all sequences, the noncoding strand is shown in its 5′-3′ orientation.  
       [0341] The 5′ end is proximal to the 16S rRNA gene, the 3′ end proximal to the 23S rRNA gene.  
       [0342] It is to be pointed out that each nucleic acid sequence of the spacer region between the 16S and 23S rRNA genes of each respective organism referred to in FIGS.  1  to  10  (except the one of  E. coli ) is new.  
       [0343] In FIG. 1 the nucleic acid sequence alignment of the 16S rRNA proximal end of the spacer region between the 16S and 23S rRNA gene of  Neisseria gonorrhoeae  strains NCTC 8375 (top line) and ITM 4367 (bottom line) is shown.  
       [0344] In FIG. 2 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Bordetella pertussis  ATCC 10380 (top line) and  Bordetella bronchiseptica  NCTC 452 (bottom line) is shown.  
       [0345] In FIG. 3 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Neisseria meningitidis  NCTC 10025 (top line) and  Neisseria gonorrhoeae  NCTC 8375 (bottom line) is shown.  
       [0346] In FIG. 4 the nucleic acid sequence alignment of the spacer region between the 16S and 235 rRNA of  Neisseria gonorrhoeae  NCTC 8375 (top line) and  Bordetella pertussis  ATCC 10380 (bottom line) is shown.  
       [0347] In FIG. 5 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Branhamella catarrhalis  ITM 4197 (top line) and  Neisseria gonorrhoeae  NCTC 8375 (bottom line) is shown.  
       [0348] In FIG. 6 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Haem philus ducreyi  CIP 542 (top line) and  Escherichia c li  (bottom line) is shown.  
       [0349] In FIG. 7 the nucleic acid sequence alignment of the spacer r gi n b tween the 16S and 23S rRNA of  Branhamella catarrhalis  ITM 4197 (top line) and  Moraxella nonliquefaciens  ATCC 19975 (bottom line) is shown.  
       [0350] In FIG. 8 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Haemophilus influenzae  (biogroup influenzae) NCTC 8143 (top line) and  Haemophilus influenzae  (biogroup aegyptius) ITM 859 (bottom line) is shown.  
       [0351] In FIG. 9 the nucleic acid sequence alignment of the spacer region between the 16S and 23S rRNA of  Streptococcus pneumoniae  S90-5122 (top line) and  Streptococcus agalactiae  U90-2817 (bottom line) is shown.  
       [0352] In FIG. 10 the nucleic acid sequence alignment of the 23S rRNA proximal end of the spacer region between the 16S and 23S rRNA of  Campylobacter jejuni  ATCC 33560 (top line) and  Campylobacter coli  ATCC 33559 (bottom line) is shown.  
       [0353] The strains used can be obtained at the respective culture collections:  
       [0354] ATCC: American Type Culture Collection, Rockville, Md., USA.  
       [0355] CIP: Collection de l&#39;Institut Pasteur, Paris, France.  
       [0356] ITM: Institute of Tropical Medicine, Antwerp, Belgium.  
       [0357] NCTC: National Collection of Type Cultures, Central Public Health Laboratory, London, United Kingdom.  
       [0358] The examples hereafter relate to the preparation of the probes of the invention and the experimental results with respect to the specificity and sensitivity of the probes using different hybridization protocols. The f flowing organisms of clinical relevance were selected:  Neisseria gonorrhoeae, Neisseria meningitidis, Branhamella catarrhalis, Haemophilus ducrevi, Haemophilus influenzae , and  Bordetella pertussis.    
       [0359] The examples illustrate that species-specific and highly sensitive probes could readily be found in the spacer region of all organisms studied. Moreover, it is shown that probes could be constructed from this region for organisms for which no species-specific and highly sensitive probe could be found in the 16S and/or 23S rRNA molecule. The methods used are essentially the same as described by ROSSAU et al., J. Gen. Microbiol.; 135: 1735-1745, 1989; or in the European patent application no 8940/045.3 unless otherwise stated. All methods used with the possible exception of enzymatical amplification of rRNA gene fragments and reversed hybridization, are currently known to people skilled in the art. The enzymatical amplification of rRNA gene fragments spanning the 16S-23S rRNA spacer region was obtained by the polymerase chain reaction technique (PCR) performed according to the recommendations given in the “Gene Amp” kit of Perkin Elmer Cetus. Nucleotides corresponding to conserved or semi-conserved regions in the rRNA molecules were used as PCR primers. The principle and protocol of the revers d dot-blot is described by Saiki et al. (1989). 
     
    
    
     EXAMPLE 1  
     [0360] Neisseria meningitidis  and  Neisseria gonorrhoeae  both are important human pathogens, responsible for meningitidis and gonorrhoeae, respectively. These organisms are very closely related and their differentiation from one another and other Neisseria species is error-prone. DNA pr bes specific for  Neisseria meningitidis  and  Neisseria gonorrhoeae  may aid in the correct differentiation between both Neisseria species and may be used for direct detection f these-species in clinical samples.  
     [0361] A number of DNA probes have been described for the detection of  Neisseria gonorrhoeae  (European Patent Application nr 0272 009 and 0337 896; URDEA et al., Clin. Chem. 35: 1571-1575, 19819; TOTTEN et al., J. Infect. Dis. 148: 462-471, 1989; DONEGAN et al., Mol. Cell. Probes 3: 13-26, 1989; KOLBERG et al., Mol. Cell. Probes 3: 59-72, 1989). However, some of these probes were found to cross-react with non- Neisseria gonorrhoeae  strains or were not highly sensitive. None of these probes were derived from the 16S-23S rRNA spacer region.  
     [0362] A DNA probe which detects  Neisseria meningitidis  strains has also been described (KOLBERG et al., Mol. Cell. Probes 3: 59-72, 1989). This probe, devised from the pilin gene of  Neisseria gonorrhoeae , was neither highly specific nor highly sensitive for  Neisseria meningitidis.    
     [0363] The sequence of the spacer region between the 16S and 23S rRNA gene of the type strains of  Neisseria gonorrhoeae  and  Neisseria meningitidis  was determined using cloned material originating from a PCR fragment spanning the spacer region. The alignment of both sequences, shown in FIG. 3, revealed several potential probe sequences.  
     [0364] An unexpected inserted sequence of about 60 base pairs was detected in the spacer region of the  Neisseria meningitidis  strain. Oligonucleotides with the following sequences were derived from this inserted sequence:  
     [0365] GGTCAAGTGT GACGTCGCCC TG NMI1  
     [0366] GTTCTTGGTC AAGTGTGACG TC NMI2  
     [0367] Also in another area of the spacer region (from base pairs 365 to 386 in the  Neisseria meningitidis  sequence in FIG. 3) a substantial degree of mismatch was revealed between  Neisseria meningitidis  and  Neisseria gonorrhoeae . From this area, two oligonucleotid probes (NMI3 and NGI1 f r the detection of  Neisseria meningitidis  and  Neisseria gonorrhoeae , respectively) were chemically synthesized:  
     [0368] GCGTTCGTTA TAGCTATCTA CTGTGC NMI3  
     [0369] CGATGCGTCG TTATTCTACT TCGC NGI1  
     [0370] These nucleotides were  32 P-labeled at their 5′ ends using polynucleotide kinase or tailed at their 3′ ends with digoxigenated UTP using terminal transferase and used as hybridization probes. As target, dot-spotted denatured genomic DNA from a large number of  Neisseria meningitidis  and  Neisseria gonorrhoeae  strains obtained from different locations and several strains from other bacterial taxa was used.  
     [0371] The hybridization-mixture was either 3×SSC, 25 mM potassium phosphate buffer, pH 7, deionized formamide (20%, v/v), Ficoll (0.02%, w/v), bovine serum albumin (0.02%, w/v), polyvinylpyrrolidone (0.02%, w/v) and sheared, denatured salmon sperm DNA (0.1 mg/ml) or the solution given in the protocol sheet of the nonradioactive DNA labeling and detection kit (Boehringer Mannheim) except that 3×SSC (1×SSC is: 0.15 M NaCl, 0.015 M sodium citrate, pH 7.0) instead of 5×SSC was used and formamide was added up to 20% (v/v). The wash solution contained 3×SSC, 20% formamide and 25 mM phosphate buffer pH 7.1.  
     [0372] The hybridization results are summarized in the table below. The hybridization and wash temperature for each probe is indicated between parenthesis. All probes tested proved to be highly specific and highly sensitive for  Neisseria gonorrhoeae  (probe NGI1) or  Neisseria meningitidis  (probes NMI1, NKI2 and NMI3).  
                                              No. positive strains/No. strains tested                                     NMI1   NMI2   NMI3   NGI1       TAXON   (45° C.)   (45° C.)   (40° C.)   (50° C.)                 Neisseria meningitidis     52/53   10/11   56/56    0/11       Neisseria sp ATCC 43831   1/1   1/1   1/1   0/1         Neisseria gonorrhoeae      0/16   0/9    0/10   10/10         Neisseria polysaccharea     0/3   —   0/3   0/3         Neisseria lactamica      0/10   —    0/10    0/10         Neisseria cinerea     0/4   —   0/4   2/4         Neisseria mucosa     0/3   —   0/3   0/3         Neisseria macacae     0/1   —   0/1   0/1         Neisseria flavescens     0/1   —   0/1   0/1         Neisseria subflava     0/2   —   0/2   0/2         Neisseria sicca     0/1   —   0/1   0/1         Neisseria elongata     0/2   —   0/2   0/2         Neisseria canis     0/1   —   0/1   0/1         Neisseria animalis     0/1   —   0/1   0/1         Neisseria denitrificas     0/1   —   0/1   0/1       Neisseria sp   0/5   —   0/4   0/3       CDC group M-5   0/1   —   0/1   0/1       CDC group EF-4a   0/1   —   0/1   0/1         Kingella denitrificans     0/2   —   0/1   0/1         Kingella kingae     0/1   —   0/1   0/1         Simonsiella muelleri     0/1   —   0/1   0/1         Simonsiella crassa     0/1   —   0/1   0/1         Simonsiella steedae     0/1   —   0/1   0/1       Simonsiella sp   0/1   —   0/1   0/1         Alysiella filiformis     0/1   —   0/1   0/1         Eikenella corrodens     0/2   —   0/2   0/2         Chromobacterium violaceum     0/1   —   0/1   0/1         Iodobacter fluviatile     0/1   —   0/1   0/1         Aguaspirilum dispar     0/1   —   0/1   0/1         Comamonas testosteroni     0/1   —   0/1   0/1         Haemophilus influenzae     0/1   —   —   —         Haemophilus ducrevi     0/1   —   0/1   0/1         Kingella indologenes     0/1   —   0/1   0/1         Moraxella lacunata     0/1   —   —   —         Moraxella nonliquefaciens     0/1   —   —   —         Moraxella catarrhalis     0/3   —   0/2   0/2         Moraxella cuniculi     0/1   —   —   —         Moraxella caviae     0/1   —   —   —         Moraxella ovis     0/1   —   —   —         Moraxella osloensis     0/1   —   —   —         Escherichia coli     0/1   0/1   0/1   0/1                  
 
     [0373] The specificity of the detection with probes NMI3 and NGI3 was also ch cked after enzymatic amplification of the spacer r gions with the following amplification primers:  
                                          TGGGTGAAGTCGTAACAAGGTA   AP16                           CAC GTC CTTCGTCGCCT   AP23          
 
     [0374] located at the 3′ end of the 16S rRNA gene and the 5′ end of the 23S rRNA gene, respectively. One hundred nanograms of genomic DNA from a strain of  Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus ducrevi, Bordetella pertussis  and  Branhamella catarrhalis  was used in the PCR reaction. After amplification, {fraction (1/10)} of the yield was loaded on an agarose gel, electrophoresed and blotted on a nylon membrane.  
     [0375] The membrane was consecutively hybridized with the probes NGI1 and NMI3.  
     [0376] Significant hybridization signals could only be detected in lanes where  Neisseria gonorrhoeae  or  Neisseria meningitidis  material was present when NGI1 or NMI3 was used as probe, respectively.  
     EXAMPLE 2  
     [0377] Bordetella pertussis  is the causative agent of whooping cough. As a result of repeated vaccination-campaigns, the disease has become a minor problem in the industrialized countries. However, in third-world countries,  Bordetella pertussis  remains a leading cause of childhood mortality.  
     [0378] Strains of three Bordetella species ( Bordetella pertussis, Bordetella parapertussis  and  Bordetella bronchiseptica ) are extremely highly related (KLOOS et al., Int. J. Syst. Bacteriol. 31:173-176, 1981; DE LEY et al., Int. J. Syst. Bacteriol. 36:405-414, 1986) and should be considered as belonging to one genospecies. This gen typical relationship is also reflected in many other characteristics f these bacteria, thereby making their phenotypical differentiati n tedious.  
     [0379] Clinical signs of pertussis often are a typical and laboratory diagnosis is needed. As yet, no sensitive, specific and rapid test exists. Culture still remains the method of choice, but recovery rates are low and the results usually are available only 3 to 7 days after inoculation (FRIEDMAN, Clin. Microbiol. Rev. 4:365-376, 1988: HALPERIN et al., J. Clin. Microbiol. 27:752-757, 1989). A DNA probe-based assay may greatly improve the diagnosis of  Bordetella pertussis  infections.  
     [0380] Probes for the detection of  Bordetella pertussis  are described in the literature (PARK et al., FEMS Microbiol. Lett. 52:19-24, 1988; McPHEAT and McNALLY, J. Gen. Microbiol. 133:323-330, 1987 and FEMS Microbiol. Lett. 41:357-360, 1987; McLAFFERTY et al., Abstracts of the Annual Meeting of the American Society for Microbiology C-168, 1986, and C-322, 1987). The probe described by McLAFFERTY et al. (1986 and 1987) is not highly specific. For the other probes described, the data presented are to scanty to infer the degree of specificity and sensitivity.  
     [0381] Part of the ribosomal RNA gene of the following strains were enzymatically amplified and cloned in a plasmid vector:  Bordetella pertussis  ATCC 10380 , Bordetella parapertussis  NCTC 5952 (type strain), and  Bordetella bronchiseptica  NCTC 452 (type strain). The cloned fragments of the different species were partially sequenced using the dideoxy chain terminati n method and their sequences were compared. The sequence information concerning the 16S rRNA gene which became available, indicated that no species-specific pr bes c uld be devised (ROSSAU et al., unpublished). H wever, as shown in the alignment in FIG. 2, a non-h mologous area (from basepairs 271 t about 300) was found in the spacer region between the 16S and 23S rRNA genes of the  Bordetella Pertussis  and the  Bordetella bronchiseptica  strain.  
     [0382] The sequence of the spacer region of th  Bordetella parapertussis  strain was virtually identical to the  Bordetella bronchiseptica  sequence (ROSSAU et al., unpublished).  
     [0383] From the area between nucleotide 271 and 295 in the spacer region of  Bordetella pertussis  a oligonucleotide probe with the following sequence was derived:  
     [0384] C:CACACCCAT CCTCTGGACA GGCTT BPI1  
     [0385] The oligonucleotide probe was chemically synthesized and labeled with digoxigenin-UTP using terminal transferase. The results obtained with dot-spotted denatured genomic DNA as target are summarized in the table below.  
                                                       Hybridization with BPI1 at 55° C.               No. positive strains/No.           TAXON   strains tested                            Bordetella pertussis     4/4             Bordetella parapertussis     0/3             Bordetella bronchiseptica     0/3             Alcaligenes denitrificans     0/1             Alcaligenes paradoxus     0/1             Oligella ureolytica     0/1             Oligella urethralis     0/1             Taylorella equigenitalis     0/1             Pseudomonas cepacia     0/1             Pseudomonas     0/1             solanacearum               Comamonas testosteroni     0/1             Neisseria meningitidis     0/1             Branhamella catarrhalis     0/1             Haemophilus influenzae     0/1                      
 
     [0386] Under the conditions used, the probe BPI1 proved to be 100% specific and 100% sensitive for  Bordetella pertussis.    
     [0387] The hybridization mixture was as described in the protocol sheet of the nonradioactive DNA labeling and detection kit (Boehringer Mannheim) except that 3×SSC (1×SSC is: 0.15 M NaCl, 0.015 M sodium citrate, pH 7.0) instead of 5×SSC was used and formamide was added up to 20% (v/v). The wash solution contained 3×SSC, 20% formamide and 25 mM phosphate buffer pH 7.1. The hybridization and wash temperature was 55° C.  
     [0388] Essentially the same result as those shown in the table ab ve were obtained when using a reversed dot-blot assay. This assay was performed as f llows:  
     [0389] One ng of bacterial DNA from a variety of strains obtained from different bacterial species was enzymatically amplified as recommended by the manufacturer of the Gene-Amp kit (Perkin Elmer Cetus) except that digoxigenin-11-dUTP (Boehringer Mannheim) was added to the amplification mixture to a final concentration of 40 μM. Thirty cycles (1 min/95° C., 1 min/50° C., 1 min/72° C.) with the primers AP16 and AP23 (see example 1) were performed in a total of 50 μl, Thereafter 5 μl of each PCR mix was added to 1 ml of hybridization mixture (composition as defined above) in the presence of a membrane to which 0.2 pool, 0.02 pmol and 0.002 pmol of probe BPI1 was fixed. The hybridization proceeded for one hour at 55° C. The wash step was performed at the same temperature for 10 min. The detection was performed as described in the non-radioactive DNA labeling and detection kit (Boehringer Mannheim). Although a distinct band could be observed in all samples examined after gel electrophoresis and ethidium bromide staining using the reversed dot-blot protocol, a clearly positive signal was obtained exclusively with samples in which  Bordetella pertussis  DNA was present.  
     EXAMPLE 3  
     [0390] Branhamella catarrhalis , also known as  Moraxella catarrhalis  or  Neisseria catarrhalis , is a fastidious, biochemically rather inert bacterium. Recently its important pathogenic potential was recognized.  
     [0391] Branhamella catarrhalis  seems to be frequently involved in serious infections of the respiratory tract (HAGER et al., Rev. Infect. Dis. 9:1140-1149, 1987). The diagnosis of  Branhamella catarrhalis  requires culture of the organism, which may be hampered due to overgrowth by less fastidious micro-organisms, and a battery f phenotypical tests to distinguish this organisms from commensals, such as Neisseria species, present in the oral cavity.  
     [0392] In some occurrences the phenotypical test are inconclusive as to the identity of the presumptive  Branhamella catarrhalis  isolate since there only are a limited number of tests which differentiate  Branhamella catarrhalis  from phenotypical similar bacteria (RIOU and GUIBOURDENCHE, Drugs 31 [suppl.3]:1-6, 1986). The use of a DNA probe based assay may considerably simplify the laboratory diagnosis of  Branhamella catarrhalis . A DNA probe for  Branhamella catarrhalis  derived from an unspecified DNA fragment and which cross-hybridized with DNA from  Neisseria caviae  was described by BEAULIEU and ROY (Abstracts of the Annual Meeting of the American Society for Microbiology, Abstract No. D-249, 1989).  
     [0393] Part of the rRNA gene of  Branhamella catarrhalis  ITG 4197 was enzymatically amplified by the polymerase chain reaction technique and cloned in a plasmid vector. The fragment spanning the 16S-23S rRNA spacer region was subsequently sequenced by the dideoxy chain termination technique. The sequence is shown in FIG. 7 (top line). From the sequence data, the following oligonucleotide was selected and chemically synthesized:  
     [0394] TTAAACATCT TACCAAAG BCI1  
     [0395] The oligonucleotide was  32 P-labeled at its 5′ end with polynucleotide kinase and used as a hybridization probe. As target, dot-spotted denatured genomic DNA of 31  Branhamella catarrhalis  strains from different locations and 19 strains of other bacterial taxa was used.  
     [0396] The hybridization-mixture was either 3×SSC (1×SSC is: 0.15 M NaCl, 0.015 M sodium citrate, pH 7.0), 25 mM potassium phosphate buffer, pH 7, deionized formamide (20%, v/v), Ficoll (0.02%, w/v), bovine serum albumin (0.02%, w/v), polyvinylpyrrolid ne (0.02%, w/v) and sheared, denatured salmon sperm DNA (0.1 mg ml-1). The wash-solution c ntained 3×SSC, 20% formamide and 25 mM phosphate buffer pH 7.1. The hybridization and wash temperature was 30° C.  
     [0397] Under the conditions used, probe BCI1 hybridized to all  Branhamella catarrhalis  strains. None of the strains tested belonging to other bacterial species gave a significant hybridization signal with the probe.  
     [0398] The non- Branhamella catarrhalis  strains tested are:  
                                                        Moraxella lacunata     ATCC 17967             Moraxella lacunata     ATCC 17952             Moraxella bovis     ITM 1601             Moraxella nonliquefaciens     ATCC 19975             Neisseria cuniculi     ITM 3388             Neisseria ovis     NCTC 11227             Neisseria caviae     ATCC 14659           Alysiella sp.   ATCC 29468             Moraxella osloensis     LMG 1043             Moraxella osloensis     ATCC 17974           “ Moraxella paraphenylpyruvica ”   LMG 5125           “ Moraxella camembertii ”   LMG 7022             Psychrobacter immobilis     LMG 6784             Acinetobacter calcoaceticus     ATCC 23055             Escherichia coli     B             Haemophilus influenzae     NCTC 8143             Eikenella corrodens     NCTC 10596             Xanthomonas maltophilia     LMG 958             Xanthomonas campestris     LMG 568                      
 
     EXAMPLE 4  
     [0399] Haemophilus ducreyi , the causative agent of chancr id, is a fastidious Gram-negative bacterium. The culture of this organism is both difficult and insensitive; yet it still is the method of choice for the diagnosis of  Haemophilus ducreyi  infections. The use of highly specific probes may obviate the culture and increase the sensitivity of the diagnosis. Cloned DNA probes for  Haemophilus ducreyi  showing weak cross-reactivity with other Haemophilus and Pasteurella species, and targeting genes coding for proteins were described by PARSONS et al. (J. Clin. Microbiol. 27:1441-1445, 1989).  
     [0400] Part of the rRNA gene of the type strain of  Haemophilus ducreyi  CIP 542 was enzymatically amplified by the polymerase chain reaction and cloned in a plasmid vector.  
     [0401] The sequence of the spacer region between the 16S and 23S rRNA gene was obtained by the dideoxy chain termination technique. From the nucleic acid sequence, the following oligonucleotide was selected and chemically synthesized:  
     [0402] TTATTATGCG CGAGGCATAT TG HDI1  
     [0403] The oligonucleotide was  32 P-labeled at its 5′ ends or tailed at its 3′ ends with digoxigenated UTP using terminal transferase and used as a hybridization probe.  
     [0404] As target, dot-spotted denatured genomic DNA of 41  Haemophilus ducreyi  strains from different locations and several strains of other bacterial taxa was used. The oligonucleotide probe hybridized exclusively to all  Haemophilus ducreyi  strains tested.  
     [0405] The hybridization-mixture was either 3×SSC, 25 mM potassium phosphate buffer, pH 7, deionized formamide (20%, v/v), Ficoll (0.02%, w/v), bovine serum albumin (0.02%, w/v), polyvinylpyrrolidone (0.02%, w/v) and sheared, denatured salmon sperm DNA (0.1 mg ml-1) or the solution given in the protocol sheet of the nonradioactive DNA labeling and detection kit (Boehringer Mannheim) except that 3×SSC (1×SSC is: 0.15 M NaCl, 0.015 M sodium citrate, pH 7.0) instead of 5×SSC was used and formamide was added up to 20% (v/v). The wash soluti n c ntained 3×SSC, 20% formamide and 25 mM phosphate buffer pH 7.1. The hybridization and wash temperature was 40° C.  
     [0406] The non- Haemophilus ducreyi  strains tested were:  
     [0407] Escherichia coli  MC 1061  
     [0408] Escherichia coli  B  
     [0409] Actinobacillus actinomycetemcomitans  NCTC 9710  
     [0410] Actinobacillus lignieresii  NCTC 4189  
     [0411] Haemophilus aphrophilus  NCTC 5906  
     [0412] Haemophilus influenzae  NCTC 8143  
     [0413] Histophilus ovis  HIM 896-7  
     [0414] Pasteurella multocida  NCTC 10322  
     [0415] Branhamella catarrhalis  ITM 4197  
     [0416] Comamonas testosteroni ATCC 17407  
     [0417] Oligella urethralis  LMG 6227  
     [0418] Neisseria gonorrhoeae  ITM 4437  
     [0419] Campylobacter jejuni  CCUG 11284  
     [0420] Acinetobacter calcoaceticus  ATCC 23055  
     [0421] Unidentified strain ITM 3565  
     EXAMPLE 5  
     [0422] The Gram-negative bacterial species  Haemophilus influenzae  can be subdivided within two biogroups:  influenzae  and  aegyptius  (Casin et al., Ann. Inst. Pasteur/Microbiol. 137B:155-163, 1986). Organisms of the  influenzae  biogroup are important respiratory tract pathogens and also the cause of meningitis and otitis in children. Biogroup  aegyptius  isolates are the causative agent of bacterial conjunctivitis in h t climates and seem to be associated with Brazilian Purpuric Fever (Brenner et al., J. Clin. Microbiol. 26:1524-1534, 1988). A rapid detection of typable and non-typable  Haemophilus influenzae  strains can be achieved with nucleic acid pr bes.  
     [0423] DNA probes for this sp cies have been described in the literatur (T rpstra t al., Scand. J. Infect. Dis. 19:641-646, 1987; Malouin et al. J. Clin. Microbiol. 26:2132-2138, 1988). None of these probes have been derived from the 165-23S rRNA spacer region.  
     [0424] Part of the rRNA gene of the type strain of  Haemophilus influenzae  NCTC 8143 was enzymatically amplified by the polymerase chain reaction and cloned in a plasmid vector.  
     [0425] The sequence of the spacer region between the 16S and 23S rRNA gene was obtained by the dideoxy chain termination technique. Prom the nucleic acid sequence, the following oligonucleotides were selected and chemically synthesized:  
                                          ACGCATCAAA TTGACCGCAC TT   HII1                           ACTTTGAAGT GAAAACTTAA AG   HII2          
 
     [0426] The oligonucleotides were  32 P-labeled at their 5′ ends and used as hybridization probes. As target, dot-spotted denatured genomical DNA of bacterial taxa was used.  
     [0427] The hybridization results with both probes are summarized in the table below. At the hybridization and wash temperatures used, probe HII1 did not hybridize to the  Haemophilus influenzae  biogroup  aegyptius  strain. Probe HII2 hybridized to strains of both biogroups. Both probes also hybridized at the indicated temperatures to 15 other clinical isolates of  Haemophilus influenzae  biogroup  influenzae  obtained from the Institute of Tropical Medicine, Antwerp, Belgium.  
     [0428] The hybridization mixture was 3×SSC, 25 mM potassium phosphate buffer, pH 7, deionized formamide (20%, v/v), Ficoll (0.02%, w/v), bovine serum albumin (0.02%, w/v), polyvinylpyrrolidone (0.02%, w/v) and sheared, denatured salmon sperm DNA (0.1 mg ml-1). The wash solution contained 3×SSC, 20% formamid and 25 mM ph sphate buffer pH 7.1.  
                                              PROBE                             HII1   HII2       TAXON   (50° C.)   (30° C.)                 Haemophilus influenzae  (biogroup  influenzae ) NCTC   +   +       8143         Haemophilus influenzae  (biogroup  influenzae ) ITM   +   +       3837         Haemophilus influenzae  (biogroup  aegyptius ) ITM 859   −   +         Haemophilus parahaemolyticus  ITM 402   −   −         Haemophilus parainfluenzae  ITM 1094   −   −         Haemophilus aphrophilus  NCTC 5906   −   −         Haemophilus ducreyi  CIP 542   −   −         Pasteurella multocida  NCTC 10322   −   −         Pasteurella picida  ATCC 17911   −   −         Actinobacillus lignieresii  NCTC 4189   −   −         Actinobacillus actinomycetemcominitans  NCTC 9710   −   −         Histophilus ovis  HIM 896-7   −   −         Pseudomonas cepacia  ATCC 25609   −   −         Acinetobacter calcoaceticus  ATCC 23055   −   −         Branhamella catarrhalis  LMG 5128   −   −         Bordetella pertussis  NCTC 8189   −   −         Escherichia coil  B   −   −         Neisseria meningitidis  NCTC 10025   −   −                  
 
     [0429] 
    
     
       
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                    (iii) NUMBER OF SEQUENCES: 104  
               
               
                   
               
               
                   
               
               
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                           (A) LENGTH: 24 base pairs  
               
               
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                 CGATGCTGCG TTATTCTACT TCGC                                            24  
               
               
                   
               
               
                   
               
               
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                 GCGAAGTAGA ATAACGACGC ATCG                                            24  
               
               
                   
               
               
                   
               
               
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                 GCGAAGUAGA AUAACGACGC AUCG                                            24  
               
               
                   
               
               
                   
               
               
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                 CGAUGCGUCG UUAUUCUACU UCGC                                            24  
               
               
                   
               
               
                   
               
               
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                 TTCGTTTACC TACCCGTTGA CTAAGTAAGC AAAC                                 34  
               
               
                   
               
               
                   
               
               
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                 GTTTGCTTAC TTAGTCAACG GGTAGGTAAA CGAA                                 34  
               
               
                   
               
               
                   
               
               
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                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7:  
               
               
                   
               
               
                 GUUUGCUUAC UUAGUCAACG GGUAGGUAAA CGAA                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 8:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 34 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8:  
               
               
                   
               
               
                 UUGGUUUACC UACCCGUUGA CUAAGUAAGC AAAC                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 9:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:  
               
               
                   
               
               
                 GGTCAAGTGT GACGTCGCCC TG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 10:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:  
               
               
                   
               
               
                 CAGGGCGACG TCACACTTGA CC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 11:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11:  
               
               
                   
               
               
                 CAGGGCGACG UCACACUUGA CC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 12:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:  
               
               
                   
               
               
                 GGUCAAGUGU GACGUCGCCC UG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 13:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:  
               
               
                   
               
               
                 GTTCTTGGTC AAGTGTGACG TC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 14:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:  
               
               
                   
               
               
                 GACGTCACAC TTGACCAAGA AC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 15:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:  
               
               
                   
               
               
                 GACGUCACAC UUGACCAAGA AC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 16:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16:  
               
               
                   
               
               
                 GUUCUUGGUC AAGUGUGACG UC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 17:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 26 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:  
               
               
                   
               
               
                 GCGTTCGTTA TAGCTATCTA CTGTGC                                          26  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 18:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 26 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18:  
               
               
                   
               
               
                 GCACAGTAGA TAGCTATAAC GAACGC                                          26  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 19:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 26 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:  
               
               
                   
               
               
                 GCACAGUAGA UAGCUAUAAC GAACGC                                          26  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 20:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 26 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20:  
               
               
                   
               
               
                 GCGUUCGUUA UAGCUAUCUA CUGUGC                                          26  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 21:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 28 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21:  
               
               
                   
               
               
                 TGCGTTCGAT ATTGCTATCT ACTGTGCA                                        28  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 22:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 28 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22:  
               
               
                   
               
               
                 TGCACAGTAG ATAGCAATAT CGAACGCA                                        28  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 23:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 28 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:  
               
               
                   
               
               
                 UGCACAGUAG AUAGCAAUAU CGAACGCA                                        28  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 24:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 28 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:  
               
               
                   
               
               
                 UGCGUUCGAU AUUGCUAUCU ACUGUGCA                                        28  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 25:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 50 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25:  
               
               
                   
               
               
                 TTTTGTTCTT GGTCAAGTGT GACGTCGCCC TGAATGGATT CTGTTCCATT                50  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 26:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 50 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26:  
               
               
                   
               
               
                 AATGGAACAG AATCCATTCA GGGCGACGTC ACACTTGACC AAGAACAAAA                50  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 27:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 50 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27:  
               
               
                   
               
               
                 AAUGGAACAG AAUCCAUUCA GGGCGACGUC ACACUUGACC AAGAACAAAA                50  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 28:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 50 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28:  
               
               
                   
               
               
                 UUUUGUUCUU GGUCAAGUGU GACGUCGCCC UGAAUGGAUU CUGUUCCAUU                50  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 29:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 34 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29:  
               
               
                   
               
               
                 TTTGCCTAAC ATTCCGTTGA CTAGAACATC AGAC                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 30:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 34 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30:  
               
               
                   
               
               
                 GTCTGATGTT CTAGTCAACG GAATGTTAGG CAAA                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 31:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 34 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31:  
               
               
                   
               
               
                 GUCUGAUGUU CUAGUCAACG GAAUGUUAGG CAAA                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 32:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 34 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32:  
               
               
                   
               
               
                 UUUGCCUAAC AUUCCGUUGA CUAGAACAUC AGAC                                 34  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 33:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 18 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33:  
               
               
                   
               
               
                 TTAAACATCT TACCAAAG                                                   18  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 34:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 18 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:  
               
               
                   
               
               
                 CTTTGCTAAG ATGTTTAA                                                   18  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 35:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 18 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35:  
               
               
                   
               
               
                 CUUUGGUAAG AUGUUUAA                                                   18  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 36:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 18 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36:  
               
               
                   
               
               
                 UUAAACAUCU UACCAAAG                                                   18  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 37:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37:  
               
               
                   
               
               
                 TTGATGTTTA AACTTGCTTG GTGGA                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 38:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38:  
               
               
                   
               
               
                 TCCACCAAGC AAGTTTAAAC ATCAA                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 39:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 39:  
               
               
                   
               
               
                 UCCACCAAGC AAGUUUAAAC AUCAA                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 40:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40:  
               
               
                   
               
               
                 UUGAUGUUUA AACUUGCUUG GUGGA                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 41:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 41:  
               
               
                   
               
               
                 TTATTATGCG CGAGGCATAT TG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 42:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42:  
               
               
                   
               
               
                 CAATATGCCT CGCGCATAAT AA                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 43:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 43:  
               
               
                   
               
               
                 CAAUAUGCCU CGCGCAUAAU AA                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 44:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44:  
               
               
                   
               
               
                 UUAUUAUGCG CGAGGCAUAU UG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 45:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45:  
               
               
                   
               
               
                 ACGCATCAAA TTGACCGCAC TT                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 46:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46:  
               
               
                   
               
               
                 AAGTGCGGTC AATTTGATGC GT                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 47:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 47:  
               
               
                   
               
               
                 AAGUGCGGUC AAUUUGAUGC GU                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 48:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48:  
               
               
                   
               
               
                 ACGCAUCAAA UUGACCGCAC UU                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 49:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49:  
               
               
                   
               
               
                 ACTTTGAAGT GAAAACTTAA AG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 50:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 50:  
               
               
                   
               
               
                 CTTTAAGTTT TCACTTCAAA GT                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 51:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51:  
               
               
                   
               
               
                 CUUUAAGUUU UCACUUCAAA GU                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 52:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 52:  
               
               
                   
               
               
                 ACUUUGAAGU GAAAACUUAA AG                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 53:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 53:  
               
               
                   
               
               
                 CCACACCCAT CCTCTGGACA GGCTT                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 54:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54:  
               
               
                   
               
               
                 AAGCCTGTCC AGAGGATGGG TGTGG                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 55:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 55:  
               
               
                   
               
               
                 AAGCCUGUCC AGAGGAUGGG UGUGG                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 56:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 25 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 56:  
               
               
                   
               
               
                 CCACACCCAU CCUCUGGACA GGCUU                                           25  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 57:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 57:  
               
               
                   
               
               
                 GTGAGAGATC ACCAAGTAAT GCA                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 58:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58:  
               
               
                   
               
               
                 TGCATTACTT GGTGATCTCT CAC                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 59:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 59:  
               
               
                   
               
               
                 UGCAUUACUU GGUGAUCUCU CAC                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 60:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 60:  
               
               
                   
               
               
                 GUGAGAGAUC ACCAAGUAAU GCA                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 61:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 20 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61:  
               
               
                   
               
               
                 AGGAACTGCG CATTGGTCTT                                                 20  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 62:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 20 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62:  
               
               
                   
               
               
                 AAGACCAATG CGCAGTTCCT                                                 20  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 63:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 20 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63:  
               
               
                   
               
               
                 AAGACCAAUG CGCAGUUCCU                                                 20  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 64:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 20 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 64:  
               
               
                   
               
               
                 AGGAACUGCG CAUUGGUCUU                                                 20  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 65:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 24 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 65:  
               
               
                   
               
               
                 GAGTTTATGA CTGAAAGGTC AGAA                                            24  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 66:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 24 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 66:  
               
               
                   
               
               
                 TTCTGACCTT TCAGTCATAA ACTC                                            24  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 67:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 24 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 67:  
               
               
                   
               
               
                 UUCUGACCUU UCAGUCAUAA ACUC                                            24  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 68:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 24 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: cDNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 68:  
               
               
                   
               
               
                 GAGUUUAUGA CUGAAAGGUC AGAA                                            24  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 69:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 21 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69:  
               
               
                   
               
               
                 AATCGAAAGG TTCAAATTGT T                                               21  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 70:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 21 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 70:  
               
               
                   
               
               
                 AACAATTTGA ACCTTTCGAT T                                               21  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 71:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 21 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71:  
               
               
                   
               
               
                 AACAAUUUGA ACCUUUCGAU U                                               21  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 72:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 21 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72:  
               
               
                   
               
               
                 AAUCGAAAGG UUCAAAUUGU U                                               21  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 73:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 73:  
               
               
                   
               
               
                 GGAAACCTGC CATTTGCGTC TT                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 74:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 74:  
               
               
                   
               
               
                 AAGACGCAAA TGGCAGGTTT CC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 75:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75:  
               
               
                   
               
               
                 AAGACGCAAA UGGCAGGUUU CC                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 76:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76:  
               
               
                   
               
               
                 GGAAACCUGC CAUUUGCGUC UU                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 77:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 27 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 77:  
               
               
                   
               
               
                 TCCACGATCT AGAAATAGAT TGTAGAA                                         27  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 78:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 27 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 78:  
               
               
                   
               
               
                 TTCTACAATC TATTTCTAGA TCGTGGA                                         27  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 79:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 27 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79:  
               
               
                   
               
               
                 UUCUACAAUC UAUUUCUAGA UCGUGGA                                         27  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 80:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 27 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 80:  
               
               
                   
               
               
                 UCCACGAUCU AGAAAUAGAU UGUAGAA                                         27  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 81:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 81:  
               
               
                   
               
               
                 TCTAGTTTTA AAGAAACTAG GTT                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 82:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 82:  
               
               
                   
               
               
                 AACCTAGTTT CTTTAAAACT AGA                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 83:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 83:  
               
               
                   
               
               
                 AACCUAGUUU CUUUAAAACU AGA                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 84:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 23 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 84:  
               
               
                   
               
               
                 UCUAGUUUUA AAGAAACUAG GUU                                             23  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 85:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 603 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85:  
               
               
                   
               
               
                 AGAGAAAGAA GGGGCTTTAG GCATTCACAC TTATCGGTAA ACTGAAAAGA TGCGGAAGA      60  
               
               
                   
               
               
                 GCTTGAGTGA AGGCAAGGTT CGCTTAAGAA GGGAAACCGG GTTTGTAGCT CAGCTGGT      120  
               
               
                   
               
               
                 GAGCACACGC TTGATAAGCG TGAGGTCGGA GGTTCAAGTC CTCCCAGACC CACCAAGA      180  
               
               
                   
               
               
                 GGGGGCATAG CTCAGTTGGT AGAGCACCTG CTTTGCAAGC AGGGGGTCAT CGGTTCGA      240  
               
               
                   
               
               
                 CCGTTTGCCT CCACCAAAAC TTTACAAATG AAAGCAAGTT TGCTGTTTTT AGCAGCTT      300  
               
               
                   
               
               
                 TTTGATTTGC GAAGTAGAAT AACGACGCAT CGATCTTTAA CAAATTGGAA AGCCGAAA      360  
               
               
                   
               
               
                 AACAAACAAA GACAATGAGT TTGTTTTGAT TTTTTATTCT TTGCAAAGGA TAAAAAAT      420  
               
               
                   
               
               
                 CTCGCAAGAG AAAAGAAAAC AAACATAGTA TTTGGGTGAT GATTGTATCG ACTTAATC      480  
               
               
                   
               
               
                 GAAACACAAA AGGCAGGATT AAGACACAAC AAAGCAGTAA GCTTTATCAA AGTAGGGA      540  
               
               
                   
               
               
                 TCAAGTTTGC TTACTTAGTC AACGGGTAGG TAAACGAAGT CAAAGAAGTT CTTGAAAT      600  
               
               
                   
               
               
                 TAG                                                                  603  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 86:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 603 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86:  
               
               
                   
               
               
                 AGAGAAAGAA GGGGCTTTAG GCATTCACAC TTATCGGTAA ACTGAAAAGA TGCGGAAGA      60  
               
               
                   
               
               
                 GCTTGAGTGA AGGCAAGGTT CGCTTAAGAA GGGAAACCGG GTTTGTAGCT CAGCTGGT      120  
               
               
                   
               
               
                 GAGCACACGC TTGATAAGCG TGAGGTCGGA GGTTCAAGTC CTCCCAGACC CACCAAGA      180  
               
               
                   
               
               
                 GGGGGCATAG CTCAGTTGGT AGAGCACCTG CTTTGCAAGC AGGGGGTCAT CGGTTCGA      240  
               
               
                   
               
               
                 CCGTTTGCCT CCACCAAAAC TTTACAAATG AAAGCAAGTT TGCTGTTTTT AGCAGCTT      300  
               
               
                   
               
               
                 TTTGATTTGC GAAGTAGAAT AACGACGCAT CGATCTTTAA CAAATTGGAA AGCCGAAA      360  
               
               
                   
               
               
                 AACAAACAAA GACAATGAGT TTGTTTTGAT TTTTTATTCT TTGCAAAGGA TAAAAAAT      420  
               
               
                   
               
               
                 CTCGCAAGAG AAAAGAAAAC AAACATAGTA TTTGGGTGAT GATTGTATCG ACTTAATC      480  
               
               
                   
               
               
                 GAAACACAAA AGGCAGGATT AAGACACAAC AAAGCAGTAA GCTTTATCAA AGTAGGGA      540  
               
               
                   
               
               
                 TCAAGTTTGC TTACTTAGTC AACGGGTAGG TAAACGAAGT CAAAGAAGTT CTTGAAAT      600  
               
               
                   
               
               
                 TAG                                                                  603  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 87:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 582 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 87:  
               
               
                   
               
               
                 AAGAGCTTGA GTGCTCGTGT CAAGTGTCCA CGCTTATCGG TTGTTGTTAT ATAGCTGCT      60  
               
               
                   
               
               
                 GATCGGTGGC TGCTGATCCG AGAGAGAAAG GTTTCGCGGG TCTGTAGCTC AGTCGGTT      120  
               
               
                   
               
               
                 AGCACCGTCT TGATAAGGCG GGGGTCGTTG GTTCGAATCC AACCAGACCC ACCAAGGT      180  
               
               
                   
               
               
                 CCTGAGAGGG AAATGGGGGT GTAGCTCAGC TGGGAGAGCG CCTGCTTTGC AAGCAGGA      240  
               
               
                   
               
               
                 TCATCGGTTC GATCCCGTTC ACCTCCACCA AAGCCTGTCC AGAGGATGGG TGTGGNNN      300  
               
               
                   
               
               
                 GACCAGAAGG CGAGAGAGCA ACGTTAGTGC TGCGAGTCAG TGTTAAGCGT TGGGTTTT      360  
               
               
                   
               
               
                 CCGACAGCTA TATATGTTCT TTAACAATTT GGAAGAAGCA CAACGTAAAG TGTTCGTT      420  
               
               
                   
               
               
                 GTAGTCGGCG CGAGTCGATG AAGACGGATA CGGGTTGTGA TTGCATGATT TTGTTCCA      480  
               
               
                   
               
               
                 TCTCAAGAAC TGGCTGGGCG GCCAAGCGTT TGGTCAGATG CTTTGAACTT ATGAACGG      540  
               
               
                   
               
               
                 CAAGCGCGAA TGAACAGCAC CTATAAGACT TTAGTGTTAT AG                       582  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 88:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 590 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 88:  
               
               
                   
               
               
                 AAGAGCTTGA GTGCTCGTGT CAAGTGTCCA CGCTTATCGG TTGTTGTTAT ATAGCTGCT      60  
               
               
                   
               
               
                 GATCGGTGGC TGCTGATCCG AGAGAGAAAG GTTTCGCGGG TCTGTAGCTC AGTCGGTT      120  
               
               
                   
               
               
                 AGCACCGTCT TGATAAGGCG GGGGTCGTTG GTTCGAATCC AACCAGACCC ACCAAGGT      180  
               
               
                   
               
               
                 CCTGAGAGGG AAATGGGGGT GTAGCTCAGC TGGGAGAGCG CCTGCTTTGC AAGCAGGA      240  
               
               
                   
               
               
                 TCATCGGTTC GATCCCGTTC ACCTCCACCA GAGCCCGTCT TGAAGATGGG AGCGGGTT      300  
               
               
                   
               
               
                 CAGGCGAGAC CAGGAAGGCG AGAGAGCAAC GTTAGTGCTG CGAGTCAGTG TTAAGCGT      360  
               
               
                   
               
               
                 GGTTTTGGCC GACAGCTATA TATGTTCTTT AACAATTTGG AAGAAGCACA ACGTAAAG      420  
               
               
                   
               
               
                 TTCGTTTAGT AGTCGACGCG AGTCGATGAA GACGGATACG GGTTGTGATT GCATGATT      480  
               
               
                   
               
               
                 GTTCCAAGTC TCAAGAACTG GCTGGGCGGC CAAGCGTTTG GTCAGATGCT TTGAACTT      540  
               
               
                   
               
               
                 GAACGGCACA AGCGCGAATG AACAGCACCT ATAAGACTTT AGTGTTATAG               590  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 89:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 654 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 89:  
               
               
                   
               
               
                 AGAGAAAGAA GAGGCTTTAG GCATTCACAC TTATCGGTAA ACTGAAAAAG ATGCGGAAG      60  
               
               
                   
               
               
                 AGCTTGAGTG AAGGCAAGAT TCGCTTAAGA AGAGAATCCG GGTTTGTAGC AGAGCACA      120  
               
               
                   
               
               
                 CTTGATAAGC GTGGGGTCGG AGGTTCAAGT CCTCCCAGAC CCACCAAGAA CGGGGGGC      180  
               
               
                   
               
               
                 AGCTCAGTTG GTAGAGCACC TGCTTTGCAA GCAGGGGGTC ATCGGTTCGA TCCCGTTT      240  
               
               
                   
               
               
                 CTCCACCAAT ACTGTACAAA TCAAAACGGA AGAATGGAAC AGAATCCATT CAGGGCGA      300  
               
               
                   
               
               
                 TCACACTTGA CCAAGAACAA AATGCTGATA TAATAATCAG CTCGTTTTGA TTTGCACA      360  
               
               
                   
               
               
                 AGATAGCAAT ATCGAACGCA TCGATCTTTA ACAAATTGGA AAGCCGAAAT CAACAAAC      420  
               
               
                   
               
               
                 AGACAAAGCG TTTGTTTTGA TTTTTTATTC TTTGCAAAGG ATAAAAAATC GCTCACAA      480  
               
               
                   
               
               
                 GAAAAGAAAA CAAACACAGT ATTTGGGTGA TGATTGTATC GACTTAACCC TGAAACAC      540  
               
               
                   
               
               
                 AAGGCAGGAT TAAGACACAA CAAAGCAGTA AGCTTTATCA AAGTAGGAAA TTCAAGTC      600  
               
               
                   
               
               
                 ATGTTCTAGT CAACGGAATG TTAGGCAAAG TCAAAGAAGT TCTTGAAATG ATAG          654  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 90:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 498 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 90:  
               
               
                   
               
               
                 ACGAAGTTAT CTGATTGGCA AGAATCCACA ACAAGTTGTT CTTTGGTAAG ATGTTTAAA      60  
               
               
                   
               
               
                 ACGGGTCTAT AGCTCAGTTG GTTAGAGCAC CGTGTTGATA ACGCGGGGGT CATAAGTT      120  
               
               
                   
               
               
                 AGTCTTATTA GACCCACCAT TTTGGGGCCA TAGCTCAGTT GGTAGAGCGC CTGCCTTG      180  
               
               
                   
               
               
                 CGCAGGAGGT CAGGAGTTCG ACTCTCCTTG GCTCCACCAA GCAAGTTTAA ACATCAAA      240  
               
               
                   
               
               
                 ATACATAAGC AATTTAAATA AGATTTCTTA TTTATGCTTT TATTTTATAA ACTGACGA      300  
               
               
                   
               
               
                 TTTATAACAT TATTTAACAA CATAGTATGA GTCTGGGTTA ATTATTTAAT TCCAACAA      360  
               
               
                   
               
               
                 AATTAACCTG GTGTTTGTAC CCAATACAAA CACCAAAAAA GTAAAGAGAA CTGAATCA      420  
               
               
                   
               
               
                 CGTAAACATA GGTGAATCGT TACACATTAC CCATACACAC CAAAGACTTC CTAGAAGT      480  
               
               
                   
               
               
                 GACTACTTGG GGTTGTAT                                                  498  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 91:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 346 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 91:  
               
               
                   
               
               
                 CCAAAATAAA GACATCACAA GTACTCACAC AGATTGTTTG ATTGTTTTAG ACAAGTCGG      60  
               
               
                   
               
               
                 ATACATCTTT AAATGTTGTC CCCATCTGTC TAGAGGCCTA GGACATCGCC CTTTCACG      120  
               
               
                   
               
               
                 GGTAACCGGG GTTCGAANCC CCGTGGACGC CATCTAAAGA TGATTTTTAT TGTCTTAT      180  
               
               
                   
               
               
                 TCTTTAAAAA AATAGAAACA AGCTGAAAAC TGAGAGATTT TCTAAAGTAG AAAGTCTG      240  
               
               
                   
               
               
                 TAATCTAAAA TCTTAGCTGA ACAAAAGCAG CTAAGTGTTT AGTCTAAATC ATTAACCA      300  
               
               
                   
               
               
                 AGTATATCAA TATGCCTCGC GCATAATAAA ATACTTGAGG TTGTAT                   346  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 92:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 549 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 92:  
               
               
                   
               
               
                 ACGAGATTAT CTGATTGGCA AGAATCCACA ACAAGTTGTT CTTAGTAGTG TAAGTTAAA      60  
               
               
                   
               
               
                 TGGGTCTATA GCTCAGTTGG TTAGAGCACC GCCTTGATAA GGCGGGGGTC ATAAGTTC      120  
               
               
                   
               
               
                 GTCTTATTAG ACCCACCATT TTGGGGTTAT AGCTCAGTTG GTAGAGCGCC TGCCTTGC      180  
               
               
                   
               
               
                 GCAGGAGGTC AGGAGTTCGA CTCTCCTTAA CTCCACCACT TACAATAAAT GAGAACTA      240  
               
               
                   
               
               
                 CAATCAAATT AGATAACATA AAATTAGATT TCTTACTTCT ACTTTATGTA GATGACTT      300  
               
               
                   
               
               
                 AATTAACTGA TGAAGTTAAT TTCAATTATT TAACAACGTA TATATGAGTC TGGGTTAA      360  
               
               
                   
               
               
                 ATTTAATTCC AACAAATAAT TAACCATTCC GTCATACTCC ACATCAAGCA TATAAAGT      420  
               
               
                   
               
               
                 AAACTTTTAG TATTGATGAT GATCGGATAA AGTAAAGAGA ACTGAATCAA GCGTAAAC      480  
               
               
                   
               
               
                 AGGTGAATCG TTACACATTA CCCATACACA CCAAAGACTT CCTAGAAGTC AGACTACT      540  
               
               
                   
               
               
                 GGGTTGTAT                                                            549  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 93:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 474 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 93:  
               
               
                   
               
               
                 CTGAAGACGA GAGACAGCGA GTGCTCACAC AGATTGGCTG ATAGTTGTAG ACAAGATTA      60  
               
               
                   
               
               
                 AAACGAAGCG AAAGCAACGT TGAAAAATAA ACGTTAAAAG ATAAAAAGAA AATAGAGT      120  
               
               
                   
               
               
                 CTTTAATTGA TGTCCCCATC GTCTAGAGGC CTAGGACATC GCCCTTTCAC GGCGGTAA      180  
               
               
                   
               
               
                 GGGGTTCGAA TCCCCGTGGG ACGCCAATTA AAGATAACTT TATTAGATTG TCTTACTG      240  
               
               
                   
               
               
                 CTTTAAAAAA TTGGAAACAA GCTGAAAACA AGAGATTTTC GAGAGAAAGT CTGAGTAG      300  
               
               
                   
               
               
                 AAGATAGGAA AGTGAGAGGA GGGAACTGAA AAGGGAACTC TAAAAACAAA ACCTGTTT      360  
               
               
                   
               
               
                 CATAAAATCT TGATTGAACA AAAGCAATCA AGTGTTTAGT TGAATGAAAA TACGCATC      420  
               
               
                   
               
               
                 ATTGACCGCA CTTTGAAGTG AAAACTTAAA GTGATTGAAA ACATTTGAGG TGAT          474  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 94:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 476 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 94:  
               
               
                   
               
               
                 CCCAAGACGA GAGACAGCGA GTGCTCACAC AGATTGGCTG ATAGTTGTAG ACAAGATTA      60  
               
               
                   
               
               
                 AAACGAAGCG AAAGCAACGT TGAAAAATAA ACGTTAAAAG ATAAAAAGAA AATAGAGT      120  
               
               
                   
               
               
                 CTTTAATTGA TGTCCCCATC GTCTAGAGGC CTAGGACATC GCCCTTTCAC GGCGGTAA      180  
               
               
                   
               
               
                 GGGGTTCGAA TCCCCGTGGG ACGCCANNNN NNNNNNNNTT TATTAGATTG TCTTACTG      240  
               
               
                   
               
               
                 CTTTAAAAAA TTGGAAACAA GCTGAAAACA AGAGATTTTC GAGAGAAAGT CTGAGTAG      300  
               
               
                   
               
               
                 AAGACAGGAA AGTGAAAAGA GGGAACTGAG AAGGAAACTC TAAAAACAAA CCTGTTTT      360  
               
               
                   
               
               
                 AAAAAAATCT TGATTGAACA AAAGTAATCA AGTGTTTAGT TGAATTAATG AGGCTGAA      420  
               
               
                   
               
               
                 TGCAGTCAAA GTACGGTATC TATTTTATAT TGAGTTTTGA AAACATTTGA NNNNNN        476  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 95:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 246 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 95:  
               
               
                   
               
               
                 AAGGATAAGG AACTGCGCAT TGGTCTTGTT TAGTCTTGAG AGGTCTTGTG GGGCCTTAG      60  
               
               
                   
               
               
                 TCAGCTGGGA GAGCGCCTGC TTTGCACGCA GGAGGTCAGC GGTTCGATCC CGCTAGGC      120  
               
               
                   
               
               
                 CATTGGTGAG AGATCACCAA GTAATGCACA TTGAAAATTG AATATCTATA TCAAATAG      180  
               
               
                   
               
               
                 ACAAGAAAAT AAACCGAAAA CGCTGTAGTA TTAATAAGAG TTTATGACTG AAAGGTCA      240  
               
               
                   
               
               
                 AAATAA                                                               246  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 96:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 279 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 96:  
               
               
                   
               
               
                 AAGGATAAGG AAACCTGCCA TTTGCGTCTT GTTTAGTTTT GAGAGGTCTT GTGGGGCCT      60  
               
               
                   
               
               
                 AGCTCAGCTG GGAGAGCGCC TGCTTTGCAC GCAGGAGGTC AGCGGTTCGA TCCCGCTA      120  
               
               
                   
               
               
                 CTCCATTGAA TCGAAAGGTT CAAATTGTTC ATTGAAAATT GAATATCTAT ATCAAATT      180  
               
               
                   
               
               
                 ACGATCTAGA AATAGATTGT AGAAAGTAAC AAGAAAATAA ACCGAAAACG CTGTGAAT      240  
               
               
                   
               
               
                 TTAATGAGTT TTCTAGTTTT AAAGAAACTA GGTTAATAA                           279  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 97:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 511 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 97:  
               
               
                   
               
               
                 TAAAATCTAA AGCAAGTATA TAAAGTAGAT TAAATATAAA ATACAAACTC TATACTTAG      60  
               
               
                   
               
               
                 TTTATTTTTA TCTTTAACTA TAAAAGAATA TACTTTAATA AATATAAATA ACATATAC      120  
               
               
                   
               
               
                 TATGTATTTA TATTTATAAT GAGATTATTT AATATATATG CTTCCTTTAG GTTTTAAA      180  
               
               
                   
               
               
                 TAAATGTTCT TTTTAATTAT CATTGTTAAG AGTCACAAGC AAGTTTTAAT AAAAACAA      240  
               
               
                   
               
               
                 TTACAGGACT TGTTAAAGGA TAAAACCTAT TTATCTTTTC TTTGGTTTAA CTTATATC      300  
               
               
                   
               
               
                 TTAATTATCT TTATTTCTAT AATAAAGAGA ATATTAGATT TAAGATTTAT AAATTAAA      360  
               
               
                   
               
               
                 CAAGTTTCAA ACTCACAGCT TAGTTGAGAC TAAATCATTT AGTTTTATAT TAAGTGTT      420  
               
               
                   
               
               
                 AATGCTTTCC GTCTTAAGAT AAAGAAGTCT TATCATAAAA ACTTTAACAA GGAAGTGA      480  
               
               
                   
               
               
                 CGTTTTAGAA TCAATAATAA AAGGTAAAAA A                                   511  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 98:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 511 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 98:  
               
               
                   
               
               
                 TAAAATCTAA AGCAAGTATA TAAAGTAGAT TAAATATAAA ATACAAACTC TATACTTAG      60  
               
               
                   
               
               
                 TTTATTTTTA TCTTTAACTA TAAAAGAATA TACTTTAATA AATATAAATA ACATATAC      120  
               
               
                   
               
               
                 TATGTATTTA TATTTATAAT GAGATTATTT AATATATATG CTTCCTTTAG GTTTTAAA      180  
               
               
                   
               
               
                 TAAATGTTCT TTTTAATTAT CATTGTTAAG AGTCACAAGC AAGTTTTAAT AAAAACAA      240  
               
               
                   
               
               
                 TTACAGGACT TGTTAAAGGA TAAAACCTAT TTATCTTTTC TTTGGTTTAA CTTATATC      300  
               
               
                   
               
               
                 TTAATTATCT TTATTTCTAT AATAAAGAGA ATATTAGATT TAAGATTTAT AAATTAAA      360  
               
               
                   
               
               
                 CAAGTTTCAA ACTCACAGCT TAGTTGAGAC TAAATCATTT AGTTTTATAT TAAGTGTT      420  
               
               
                   
               
               
                 AATGCTTTCC GTCTTAAGAT AAAGAAGTCT TATCATAAAA ACTTTAACAA GGAAGTGA      480  
               
               
                   
               
               
                 CGTTTTAGAA TCAATAATAA AAGGTAAAAA A                                   511  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 99:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 24 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 99:  
               
               
                   
               
               
                 TGGCTCAGAT TGAACGCTGG CGGC                                            24  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 100:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 21 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 100:  
               
               
                   
               
               
                 CCTTTCCCTC ACGGTACTGG T                                               21  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 101:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 101:  
               
               
                   
               
               
                 TGGGTGAAGT CGTAACAAGG TA                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 102:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 17 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 102:  
               
               
                   
               
               
                 CACGTCCTTC GTCGCCT                                                    17  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 103:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 22 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: single  
               
               
                           (D) TOPOLOGY: linear  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 103:  
               
               
                   
               
               
                 TGGGTGAAGT CGTAACAAGG TA                                              22  
               
               
                   
               
               
                   
               
               
                 (2) INFORMATION FOR SEQ ID NO: 104:  
               
               
                   
               
               
                      (i) SEQUENCE CHARACTERISTICS:  
               
               
                           (A) LENGTH: 17 base pairs  
               
               
                           (B) TYPE: nucleic acid  
               
               
                           (C) STRANDEDNESS: both  
               
               
                           (D) TOPOLOGY: both  
               
               
                   
               
               
                     (ii) MOLECULE TYPE: Genomic DNA  
               
               
                   
               
               
                    (iii) HYPOTHETICAL: NO  
               
               
                   
               
               
                     (iv) ANTI-SENSE: NO  
               
               
                   
               
               
                      (v) FRAGMENT TYPE: &lt;Unknown&gt; 
               
               
                   
               
               
                     (vi) ORIGINAL SOURCE:  
               
               
                   
               
               
                     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 104:  
               
               
                   
               
               
                 CACGTCCTTC GTCGCCT                                                    17