# Patent

## Title
snRNA gene-like transcriptional units and uses thereof

## Abstract

By a computer search for upstream promoter elements (DSE, PSE) typical of small nuclear RNA (snRNA) genes, we have identified a number of previously unrecognized, putative transcription units whose predicted products are novel noncoding RNAs with homology to protein-coding genes. By elucidating the function of one of them, we provide evidence for the existence of a sense/antisense-based gene regulation network where part of the Pol III transcriptome could control its Pol II counterpart.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a 371 of PCT/112006/000664, filed Sep. 19, 2006, which claims the benefit of Italian patent application RM2005A000475, filed Sep. 19, 2005, the contents of each of which are incorporated herein by reference.
The instant invention concerns sequences transcribed by the RNA polymerase III type III and their use for medicine, agronomy and biotechnology.
The author has identified an unknown transcription of encoding and unpolyadenylated genome elements that are synthesized by means of RNA Pol III type III promoters or of very similar elements. Other than their identification and molecular characterization, said new transcription units were functionally analyzed and their regulative features were identified. Each transcription unit is functionally related to a specific RNA Pol II transcripts giving rise to specific sense/antisense sequence molecules.
BACKGROUND ART
Recent advances in mammalian genome studies are bringing to light the occurrence of a widespread transcription of non-coding (nc) regions devoted to the regulation of the protein coding genome expression [1-4]. The mechanisms of action of these transcripts are various and of different nature, although all of them are devoted to the regulation of fundamental genetic pathways involved in the determination of the cell phenotype. The concomitant evolution of non-coding regulatory transcripts and proteins that target different RNA:RNA or RNA:DNA complexes emphasizes the importance to study the regulatory processes mediated by nucleic acids interactions. It's now clear that either in procaryotes as well as in eukaryotes different ncRNAs can act in cis and be contemporaneously regulated in trans by other non-coding transcripts. The simultaneous occurrence of cis and trans regulatory elements bring to light the complexity of this network where the coexistence of different non-coding RNAs plays a key role in the control of other targets gene expression [5]. In this context a prominent role is played by the enlarging family of microRNAs (miRNAs) that act at post transcriptional level by inhibiting the translation of protein coding genes [6]. The known miRNAs, as protein-coding mRNAs, are synthesized as polyadenylated precursor molecules by the RNA Polymerase II transcription machinery [7]. Considering that the vast majority of the tools used in molecular biology are based on transcript collections obtained by oligo-dT RT-PCR (thus encompassing only polyadenylated RNA Polymerase II products) a wide contribution of non-polyadenylated transcripts to the human transcriptome has been shown [8]. However, the role of such transcripts in Pol II transcriptome expression regulation remains largely unexplored.
Among the non-coding elements one of the most investigated has been the Alu class of repetitive sequences that represents about one tenth of the whole human genome. Although it is not yet possible to discern a peculiar Alu's role these short transcripts has been shown to be involved in several biological processes such as RNA editing (where Alus are preferential sites for A to I RNA editing thus having profound implications either in gene expression regulation as well as in the mammalian genome evolution) [9], alternative splicing (internal exons that contain an Alu sequence are almost always alternatively spliced) [10], chromosomal recombination (the recombination between Alu elements is at the base of many genomic deletions associated with many human genetic disorders) [11], gene expression regulation (functioning as naturally occurring antisense RNAs) [12], cell stress response (such as heat shock response and/or translation inhibition) [13] and as putative miRNAs targets [14]. However, although the physiological role of Alus and all the other 7SL-derived transcripts needs to be further studied in detail, the fact that their transcription is RNA Polymerase (Pol) III-dependent bring to light a previously unexpected role in gene expression regulation of this enzyme that would need to be investigated in detail.
In this work we focus on a specific class of non-coding RNAs starting from a theoretical hypothesis on their putative function. In fact, starting from the observation that RNA Polymerase (Pol) III is specialized in transcription of non coding ncRNA genes, we postulated the presence in the genome of a large number of Pol III (or Pol III-like) transcription units each specifically regulating one (or more) specific Pol II genes, thus constituting functional “co-gene”/gene pairs.
DESCRIPTION OF THE INVENTION
Therefore it is an object of the invention a nucleic acid molecule comprising a nucleotide sequence that is characterized by:
being transcribed by an RNA polymerase III,
it does not undergone any polyadenylated tail addition (as for Pol II transcribed genes) and
it is able to modulate the expression of one or more specific RNA polymerase II-transcribed target genes.
Preferably said nucleotide sequence comprises a sequence of at least 50 nucleotides that is at least 70% identical to a fragment of one of the strands of the specific RNA polymerase II-transcribed target genes.
More preferably said sequence of at least 50 nucleotides is in a sense or an antisense configuration with respect to the fragment of one of the strands of the specific RNA polymerase II-transcribed target genes.
In a particular aspect the nucleic acid of the invention is comprised in one of the sequences from SEQ ID No. 51 to SEQ ID No. 84, preferably the sequence of at least 50 nucleotides that is at least 70% identical to a fragment of one of the strands of the specific RNA polymerase II-transcribed target gene is comprised in one the underlined fragments of the sequences from SEQ ID No. 51 to SEQ ID No. 84.
It is another object of the invention an expression vector comprising the nucleic acid according to the invention.
It is another object of the invention an array for the detection of specific nucleic acid sequences containing a repertoire of nucleic acids according to the invention.
It is another object of the invention the use of the nucleic acid according to the invention to modulate the expression of RNA polymerase II transcribed genes.
It is another object of the invention the use of the nucleic acid according to the invention to identify a target sequence for treatment and/or prevention of a molecular pathology, preferably an age related pathology, including Alzheimer disease; alternatively the pathology is caused by an alteration of cell proliferation, preferably the pathology is a tumor associated pathology.
It is another object of the invention a nucleic acid comprising at least one sequence being able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described, preferably the sequence being able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described is a promoter sequence.
In a particular aspect the sequence being able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described is comprised in one of the sequences from SEQ ID No. 51 to SEQ ID No. 84. Preferably the sequence being able to modulate the RNA polymerase III mediated expression of the nucleic acid according to claims 1 to 5 is comprised in the bold regions of sequences from SEQ ID No. 51 to SEQ ID No. 84.
It is another object of the invention the use of the nucleic acid comprising the sequence being able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described to modulate the expression of one or more specific RNA polymerase II-transcribed target genes.
It is another object of the invention the use of the nucleic acid comprising the sequence able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described to identify a target sequence for treatment and/or prevention of a molecular pathology, preferably the pathology is an age related pathology, including Alzheimer disease. Alternatively the pathology is caused by an alteration of cell proliferation, preferably the pathology is a tumor associated pathology.
It is another object of the invention a vector comprising the nucleic acid comprising the sequence able to modulate the RNA polymerase III mediated expression of the nucleic acid as above described to get expression or silencing of a RNA polymerase II transcribed specific nucleotide sequence.
The invention shall be described in the following non limitative examples, by referring to figures.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1) A: Human CENP-F gene structure as resulting from GI:89161185 (region 212843155-212904537). B: The position of the 21A antisense homologous regions are reported together with their percentage of identity. C: Sequence alignment of 21A/CENP-F homologous regions. The upper sequence is CENPF (SEQ ID NO. 87). The lower sequence is fragment of 21A (SEQ ID NO. 88).
FIG. 2) A: Northern Blot analysis of Human Skin Fibroblasts and HeLa cells. Results show two bands: the first (detected at about 300 nt) being the 21A endogenous product and the second (of a very high molecular mass) representing CenPF mRNA. B: 21A-specific RT-PCR amplification. As expected for non-polyadenylated transcripts an efficient amplification product was obtained only in the random hexamers-primed reactions. C: Promoter activity transfection assay. A specific luciferase silencing hairpin (SEQ ID No. 86) is transcribed by six novel PSE/DSE-dependent promoter elements (11A, 14A, 21A, 29A, 38A, 51A). pGL3+pRL: negative control; pSHAG-U6: canonical Pol III promoter; No Promoter: hairpin without PSE/DSE-dependent promoter thus resulting transcriptionally inactive. A schematic view of the silencing constructs including the hairpin nucleotide sequence is enclosed. D, E: Promoter activity transfection assay in presence/absence of 20 μM ML-60218 cell-permeable Pol III inhibitor or 10 pg/ml α-amanitin Pol II specific inhibitor. Results are reported as luciferase emission of treated versus untreated samples.
FIG. 3) A-D: Constructs structures. p21A: whole transcription unit; p21A-1: promoter region. p21A-2: transcription region; pMock; empty vector, p: PSE Element. d: DSE Element. t: TATA box. E-H: CENP-F protein expression level after 0, 24, 48 and 72 hours of constructs transfection. s: anti-CENP-F Antibody. 1: anti-Tubulin Antibody (Indicating that equal amounts of proteins were loaded). Striped columns: Quantitative determination of CENP-F expression modulation as determined by Western blot analysis. Full columns: Quantitative determination of CENP-F mRNA expression modulation as determined Real Time RT-PCR analysis. I-N: 21A RNA level in transfected samples indicating that the exogenous 21A expression inversely correlates with CENP-F protein expression. O: Dissociation curve of 21A amplification products. A: 21A-transfected HeLa cells. B: Untransfected HeLa cells showing the very low basal 21A transcription level.
FIG. 4) A: Proliferation inhibition of HeLa cells after 48 hours of 21A constructs transfection. Results emphasize the specificity of the Alu Jb-containing regions as proliferation inhibitors. B: Proliferation increase of HeLa cells after 48 hours of pAnti-21A and si21A transfection. siEx-FABP: unrelated chicken-specific siRNA (negative control). C, D: Anti-21A construct structure: the transcript region is inverted and the construct maintains 21A promoter as well as its termination site. si21A:siRNA 21A-specific. CENP-F protein expression level after 0, 24 and 48 hours of constructs transfection. s: anti-CENP-F Antibody. 1: anti-Tubulin Antibody (Indicating that equal amounts of proteins were loaded). Striped columns: Quantitative determination of CENP-F expression increase as determined by Western blot analysis. Full columns: Quantitative determination of CENP-F mRNA expression modulation as determined Real Time RT-PCR analysis.
FIG. 5) Mouse NIH-3T3 cells proliferation rate after transfection of 21A constructs. No proliferation decrease was observed.
FIG. 6) Real-Time RT PCR analysis of 21A endogenous RNA in different cell types. Striped columns: 21A RNA; Full columns: 5s rRNA. The dissociation curve of 21A amplification product in PBL is reported.
FIG. 7) Graphic representation of the total number of DSE consensus sequences in all the putative promoter sequences (Y axis) versus the distancies from their neighbouring PSE elements (as grouped in 50 bp long sequence classes) (X axis). As expected a high frequency of DSE consensus is associated to the distance of about 200 base pairs from the PSE. As evidenced by the trend line (polynomial) the DSE frequencies significantly decrease at about 800 base pairs upstream the PSE; this roughly suggests a PSE/DSE functional relationship in these putative promoters.
FIG. 8) Four transcripts (11A, 20A, 21A, 29A) showed a δG value significantly lower than all the others (δG<−100). A statistical analysis of such δG differences was performed bringing to light a group of transcripts (11A, 20A, 21A, 29A) whose δG is significantly lower than expected (Student' t TEST, 33 degrees of freedom, a significance level=0.1 corresponding to P-value 0.0001) thus keeping in line with their physiologically functional molecular organization.



MATERIALS AND METHODS
Databases and Searches
All the sequence searches and alignments were carried out taking advantage of the Basic Local Alignment Search Tool of the National Center for Biotechnology Informations (“BLAST”) at the web site for the (U.S.) National Center for Biotechnology Information. The sequences used as query were the following: H1 PSE-nCACCATAAAnGTGAAAn (SEQ ID No. 1) or nTTTCACnTTTTATGGTGn (SEQ ID No. 2), U6 PSE (Acc No: M14486) CTTACCGTAACTTGAAAGT (SEQ ID No. 3), 7SLPSE (as reported in PMID: 2011518) TTGACC-TAAGTG (SEQ ID No. 4), DSE (Oct1 consensus sequence)-ATTTGCAT (SEQ ID No. 5) or ATGCAAAT (SEQ ID No. 6) with or without a single base of mismatch.
Cell Culture, Transfection and Luciferase Assay
For transient transfections Hela cells (grown in DMEM supplemented with 10% FCS), were grown in multiwell Petri dishes 16 hours before transfection. The expression [21A, 21A(1), 21A(2), 21A(3)] constructs containing the regions of interest cloned in the pTopo vectors (Invitrogen) were introduced into the cells using the Fugene 6 transfection reagent (Roche) according to the manufacturer's instructions. A plasmid Expressing Luciferase was used as control of transfection efficiency (to which all the results were normalized). 24, 48 and 72 hours after transfection cells were harvested and firely luciferase activity was measured by Dual-Luciferase reporter assay system (Promega). manufacturer's protocol. In order to specifically inhibit RNA Polymerase III and/or RNA Polimerase II, a cell-permeable chlorobenzenesulfonamide (ML-60218) (Calbiochem, California USA) and/or α-amanitin (Roche Diagnostics GmbH, Germany) were used at the concentration of 20 μM and 10 μg/ml respectively in the medium for 25 h (ML-60218) and 12 h (α-amanitin) before the luciferase activity detection.
RNAi-Silencing Assay.
In order to test the promoter activity of the novel transcription units we prepared six plasmid constructs expressing a firefly luciferase silencing hairpin (obtained by Gregory Hannon's Laboratory-Cold Spring Harbor Laboratories) which transcription was driven by the 11A, 14A, 21A, 29A, 38A, 51A promoters respectively. The hairpin sequence [targeting a firefly luciferase mRNA from a co-transfected expression plasmid (Promega)] is:







5′GGAUUCCAUUCAGCGGAGCCACCUGAUGAAGCUUGAUCGGGUCUCGCU


 


GAGUUGGAAUCCAUU-3′.






Oligos used to subclone the novel Pol III Type III promoters within Not I/HinD III restriction sites (in capital) were the following:








11AFprom Not I:


(SEQ ID No. 7)


5′-atgcGCGGCCGCatttgcatgtcgctatgtg-3′


 


11ARprom HinDIII:


(SEQ ID No. 8)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccacgcact


 


cagctcgtg-3′


 


14AFprom Not I:


(SEQ ID No. 9)


5′-atgcGCGGCCGCaactgatgtatgattatatctt-3′


 


14ARprom HinDIII:


(SEQ ID No. 10)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccattatta


 


tctcctttgttctgt-3′


 


21AFprom Not I:


(SEQ ID No. 11)


5′-atgcGCGGCCGCacagctgtagcagatgct-3′


 


21ARprom HinDIII:


(SEQ ID No. 12)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccaccacac


 


ttggtcaactat-3′


 


29AFprom Not I:


(SEQ ID No. 13)


5′-atgcGCGGCCGCttctcacctaaaggagtc-3′


 


29ARprom HinDIII:


(SEQ ID No. 14)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccttctaat


 


cctcctaagatca-3′


 


38AFprom Not I:


(SEQ ID No. 15)


5′-atgcGCGGCCGCttcactaagatccagtgc-3′


 


38ARprom HinDIII:


(SEQ ID No. 16)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccgattcat


 


gaacacagaatatt3′


 


51AFprom Not I:


(SEQ ID No. 17)


5′-atgcGCGGCCGCgttgaacatttaactctgtat-3′


 


51ARprom HinDIII:


(SEQ ID No. 18)


5′-gatcAAGCTTcatcaggtggctcccgctgaattggaatccctcatgg


 


cacttggagat-3′






In this analysis the above constructs were co-transfected with a pGL3 plasmid (Promega) expressing Firefly (ff1) Luciferase as target to be silenced and with a pRL plasmid (Promega) expressing a Renilla Luciferase to which all the determinations were normalized. 24, 48 and 72 hours after transfection cells were harvested and firely/Renilla luciferase activities were measured by Dual-Luciferase reporter assay system (Promega) according to the manufacturer's protocol.
Plasmid Constructs Generation and Sequencing
The plasmid constructs p21A, p21A(1), p21A(2), p21A(3) were generated amplifying from a genomic DNA preparation the regions of interest; the PCR products were then subcloned in a pTOPO Vector (Invitrogen) following manufacturer's instructions. The oligos used to generate p21A PCR fragments were the following:







(SEQ ID No. 19)








21A Forward:
5′-GGAAATCTTACCTTCCTGCC-3′


 







(SEQ ID No. 20)








21A Reverse:
5′-TGGCTAGGTCATGTGACCAT-3′


 







(SEQ ID No. 21)








21A(1) Forward:
5′-GGAAATCTTACCTTCCTGCC-3′


 







(SEQ ID No. 22)








21A(1) Reverse:
5′-TTCATTCATTCATTCATTGATTCAC-3′


 







(SEQ ID No. 23)








21A(2) Forward:
5′-CAGCTGCAGCAGATGCTAGCAGGGC-3′


 







(SEQ ID No. 24)








21A(2) Reverse:
5′-TGGCTAGGTCATGTGACCATTC-3′


 







(SEQ ID No. 25)








21A(3) Forward:
5′-CAATCCTCAGAAATTTTCAACTGCC-3′


 







(SEQ ID No. 26)








21A(3) Reverse:
5′-TGGCTAGGTCATGTGACCATTC-3′


 






The plasmid constructs pAnti-21A was generated amplifying the transcribed region from p21A plasmid using the following oligos:










Anti-21A Terminator-containing Forward:







(SEQ ID No. 27)









5′-CTGAAAAAGTAGTCCCAGCACTTTG-3′


 



Anti-21A Bam HI-containing Reverse:







(SEQ ID No. 19)









5′-ATGCGGATCCGAGACAGGGTCTTGCTC-3′






thus generating the transcribed region in anti-sense configuration. The pAnti-21A promoter was obtained by amplifying p21A promoter with the following oligos:










21A Forward:







(SEQ ID No. 19)









5′-GGAAATCTTACCTTCCTGCC-3′


 



p21A Bam HI-containing Reverse:







(SEQ ID No. 28)









5′-ATGCGGATCCGAGCCACCACACTTGGTC-3′.






The PCR products were digested with the restriction enzyme Bam HI, purified by gel electrophoresis and ligated by T4 ligase (Invitrogen). The insert obtained was then subcloned in pTOPO vector (Invitrogen) following manufacturer's instructions. Prior to transfection all the plasmids were sequenced by DNA Sequencing Kit (Applied Biosystems) following manufacturer's instructions.

RT-PCR Reactions

In order to isolate and sequence a partial 21A cDNA ve performed different RT-PCR reactions. Starting from about 5 μg of total RNA, cDNA was synthesized by using an Oligo(dT)12-18 primer or a random hexamers mix and a Superscript first-strand synthesis system for RT-PCR (Invitrogen). cDNAs were diluted 10-50 times, then subjected to PCR reactions. The oligo used to isolate 21A RT-PCR product were: oligo forward 21AF 5′gctcacgtagtcccagcacttt-3′ (SEQ ID No. 29) and oligo reverse 21AR 5′-actatgttgcccaagctggtct-3′ (SEQ ID No. 30).

PCR products were separated on 1.5-2% agarose gel. The DNA bands were cut, purified by the DNA Gel Extraction Kit (Millipore) and sequenced.

2.8. Real-Time Quantitative RT-PCR

The RNA for 21A was measured by real-time quantitative RT-PCR using PE ABI PRISM@7700 Sequence Detection System (Perkin Elmer) and Sybr Green method. The sequences of 21A forward and reverse primers as designed by the Primer Express 1.5 software were 5′-GCTGAGGCAGGAGGATCACT-3′ (SEQ ID No. 31) and 5′-GCACTACCACACCCAGCTAATTTT-3′ (SEQ ID No. 32). The sequences of CENP-F forward and reverse primers were 5′-CTGCAGAAAGAACTCTCTCAACTTC-3′ (SEQ ID No. 33).

and 5′-TCAACAATTAAGTAGCTGGAACCA-3′ (SEQ ID No. 34). For endogenous control the expression of Glyceraldehyde 3 phosphate dehydrogenase (GAPDH) gene was examined. The sequences for human GAPDH primers were 5′-GAAGGTGAAGGTCGGAGTC-3′ (SEQ ID No. 35) and 5′-GAAGATGGTGATGGGATTTC-3′ (SEQ ID No. 36). The sequences for human 5s rRNA primers were 5′-TACGGCCATACCACCCTGAA-3′ (SEQ ID No. 37) and 5′-GCGGTCTCCCATCCAAGTAC-3′ (SEQ ID No. 38). Relative transcript levels were determined from the relative standard curve constructed from stock cDNA dilutions, and divided by the target quantity of the calibrator following manufacturer's instructions.

Anti-21A siRNA Synthesis

The Anti-21A siRNA was synthesized against a region of the 21A transcript of no homology with CENP-F so that the silencing effect was specific for the Pol III regulatory RNA and did not interfere with CENP-F mRNA stability. The siRNA synthesis was carried out taking advantage of the siRNA Construction Kit (Ambion, USA) according to the manufacturer's protocol. The Sense/2Antisense oligos used were: 5′-aaGTGTGGTGGCTCACcctgtctc-3′ (SEQ ID No. 39) and 5′-aaGTGAGCCACCACACcctgtctc-3′ (SEQ ID No. 40).
Proliferation Assay
We tested proliferation of HeLa cells transfected with 21A, 21A-1, 21A-2, 21A-3, Anti-21A constructs plating 5×105 cells per well in round-bottomed 96-well plate, incubated for 24/48/72 hours after transfection and pulsed with 3H thymidine (1.0 μCi/10 μl/well) (Amersham Biosciences) for the last 18 hours. We harvested the cells and evaluated cell proliferation by counting the thymidine uptake. We calculated the averaged proliferation rate, measured as counts per minute (cpm), and standard deviation (SD) for the triplicate wells of each sample.
RNA Isolation and Northern Blot Analysis
Based on a single step acid-phenol guanidium method, total RNA was extracted using TRIzol reagent (Invitrogen) according to the manufacture's protocol. Total RNAs, from HeLa cells, were electrophoresed through 1.5% agarose gels in the presence of formaldehyde and blotted onto Hybond N membranes (Amersham). The blot was hybridized with an 85 bp long probe contained the region from nucleotide 1194 to nucleotide 1278 of the 21A reported sequence (see Table 1) spanning a region internal to the transcript and complementary (96%) to part of the CenPF mRNA. The probe was obtained by PCR (using the 21A plasmid construct as template) using the following oligos: 21AF 5′-GCTCACGTAGTCCCAGCACTTT-3′ (SEQ ID No. 41); 21AR 5′-AGACCAGCTTGGGCAACATAGT-3′ (SEQ ID No. 42). Blot prehybridizations was performed at 65° C. for 2 h in 333 mM NaH2PO4 pH 7.2, 6.66% Sodium Dodecyl Sulphate and 250 mg/ml denatured salmon sperm DNA. Blot hybridization was performed at 65° C. for IS hours in the same solution containing 106 cpm/ml of denatured and labeled probes. After hybridization the blots were washed twice at 65° C. for 30 min in 0.2% sodium dodecyl sulphate, 2×SSPE and once at 65° C. for 30 min in 0.2% sodium dodecyl sulphate, 0.2×SSPE. Membranes were exposed to autoradiographic films for 24/48 hours and then developed.

2.4 Real-Time Quantitative RT-PCR

Total RNA preparations from different CENP-F (Centromeric Protein F) (Acc. n°NM016343) samples was subjected to reverse transcription by SuperScript II First Strand Synthesis Kit (Invitrogen) following manufacturer's instructions. The cDNA obtained was measured by real-time quantitative RT-PCR using PE ABI PRISM@ 7700 Sequence Detection System (Perkin Elmer). The sequences of forward and reverse primers as designed by the Primer Express 1.5 software were 5′-CTGCAGAAAGAACTCTCTCAACTTC-3′ (SEQ ID No. 43) and 5′-AGTTGTTAATTCATCGACCTTGGT-3′(SEQ ID No. 44). The TaqManTM fluorogenic probe used was 5′-FAM-AGTACCTGTTTTCTGCTTCTCCTGTGCAGC-TAMRA-3′ (SEQ ID No. 45).
The probe was placed at the junction between two exons. During PCR amplification, 5′ nucleolytic activity of Taq polymerase cleaves the probe separating the 5′ reporter fluorescent dye from the 3′ quencher dye. Threshold cycle, CT, which correlates inversely with the target mRNA levels, was measured as the cycle number at which the reporter fluorescent emission increases above a threshold level. For endogenous control the expression of Glyceraldehyde 3 phosphate dehydrogenase (G3PDH) gene was examined by quantitative RT-PCR as described above. The sequences for human GAPDH primers and probe were 5′-GAAGGTGAAGGTCGGAGTC-3′ (SEQ ID No. 46), 5′-GAAGATGGTGATGGGATTTC-3′ (SEQ ID No. 47) and 5′-TET-CAAGCTTCCCGTTCTCAGCC-TAMRA-3′ (SEQ ID No. 4S).

Relative transcript levels were determined from the relative standard curve constructed from stock cDNA dilutions, and divided by the target quantity of the calibrator following manufacturer's instructions.

Western Blot Analysis

Equal amounts of proteins (10 μg/sample) from each sample were loaded on standard 4-12% NU-PAGE gradient gels (Invitrogen S.r.l., Milano, Italy). Blotting onto Protran nitrocellulose membranes (Schleicher & Schuell, Dassel, Germany) was performed in the X-Cell Sure LockTM Electrophoresis Cell (Invitrogen S.r.l.), according to the manufacturer's instructions. The membranes were saturated overnight in 3% non-fat milk in TTBS buffer (500 nM NaCl; 20 mM Tris/Cl, pH 7.5; 0.05% Tween-20) and incubated for 4 hours at room temperature with the human Anti-Mitosin/CenPF ab90 (ABCAM, Cambridge, UK) and/or anti-Alpha Tubulin (Sigma, Missouri USA) mouse monoclonal antibodies. The Anti-Mitosin antibody recognized a weak signal at a very high apparent molecular mass (350-400 Kda) while the Anti-Alpha Tubulin showed a clear signal at 45 KDa. The immunoreactive band was revealed by an alkaline phosphate conjugated affinity-purified monoclonal anti-rabbit mouse IgG (Sigma-Aldrich Inc.) and (in the experiment indicated in FIG. 1C) the ECL detection system (Amersham, UK) or (in the experiment indicated in FIG. 1E) the alkaline phosphatase substrate BCIP/NBT (ICN Biomedicals, Aurora, Ohio, USA).
Anti-21A siRNA Synthesis
The Anti-21A siRNA was synthesized against a region of the 21A transcript of no homology with CENP-F so that the silencing effect was specific for the Pol III regulatory RNA and did not interfere with CENP-F mRNA stability. The siRNA synthesis was carried out taking advantage of the siRNA Constriction Kit (Ambion, USA) according to the manufacturer's protocol. The Sense/Antisense oligos used were: 5′-aaGTGTGGTGGCTCACcctgtctc-3′ (SEQ ID No. 49) and 5′-aaGTGAGCCACCACACcctgtctc-3′(SEQ ID No. 50).
Results
In Silico Identification of a Novel Set of snRNA Gene-Like Transcriptional Units in the Human Genome
To test our hypothesis we focused on Pol III Type III extragenic promoters, that are located upstream of the transcribed region. We screened the human genome for regions containing the consensus sequences characteristic of Pol III Type III promoters: the Proximal Sequence Element (PSE) and the Distal Sequence Element (DSE) [15, 16]. As first we tested the PSE sequences of three well characterized Pol III Type III non-coding (nc) RNAs (U6, H1, 7SL) for their ability to identify a large number of similar (if not equal) elements in the human genome by using BLAST (Basic Local Alighment of Sequence Tags) algorithm as bioinformatic tool (available at the web site for the (U.S.) National Center for Biotechnology Information; “Short Nearly Exact Matches” option, “Homo sapiens” organism database). (For sequences used as query see Materials and Methods). Interestingly while the first search with U6 and 7SK did not identify a significant number of homologous regions scattered throughout the genome the H1 consensus elements shared a high homology with 60 novel putative consensus sequences. Among these we selected (by a BLAST analysis) those who contained a DSE consensus sequence within an arbitrarily defined distance of 1000 base pairs upstream the PSE. Results evidenced 33 putative novel PSE/DSE-dependent promoters. In order to test the functional relationship between the occurrence of the PSE and the DSE consensus elements within that defined genomic distance we examined the frequency of the DSE consensus elements occurrence versus the PSE-DSE distance in the whole pool of novel promoters. Results pointed out an inverse correlation between the DSE occurrence and its distance to the PSE. A very high frequency of DSE elements was associated to the distance of a nucleosome (about 200 bp) from the PSE that significantly decrease at about 800 base pairs to the PSE [17]. Although the restricted number of putative DSE elements did not permit a proper statistical analysis the inverse correlation between DSE frequency and DSE-PSE distance was taken as preliminary indication of their functional relationship in these novel promoters (FIG. 7).
However, since the Pol III Type III promoters were at the base of our search some of their structural features needed to be considered: i) the occurrence of a PSE consensus sequence does not constitute per se the minimal Pol III Type III promoter that is, on the contrary, the result of the simultaneous occurrence at an appropriate distance of the PSE and an A/T rich element (TATA box). In fact, it has been clearly demonstrated that the occurrence of a PSE consensus that lacks a downstream A/T rich element makes the promoter readable by RNA Pol II such as in the case of snRNA U2 [16]. In this context the transcription start site is not relevant for the choice of the RNA Polymerase at least in humans although it seems to be of fundamental importance in Xenopus [18]. Therefore the putative transcription units identified by our search might thus be transcribed either by Pol II or by Pol III, depending on the occurrence of a functional A/T rich region downstream the PSE. The further occurrence of a TATA box-like consensus sequence downstream the PSE in a large part of the novel element collection further support a canonical Pol III Type III structure pointing toward their Pol III-dependency. Altogether these findings brought to light 33 novel putative transcription units whose promoter organization is compatible with Pol III transcription (Table 1).
Table 1

    i) The predicted TATA box, PSE and DSE consensus sequences (in sense as well as in antisense configurations) are indicated in bold.
    ii) The putative transcribed regions are underlined and arbitrary predicted as starting from the 21th nucleotide starting from the predicted TATA box. A 4×T repeat was considered as stop although events of “read-through” are possible and documented in literature.
    iii) The 21A region in Antisense configuration with respect to CenPF mRNA is indicated in italic.
    iv) Single strand sequences, complementary strands deducible









Human Genome Map 14q11.2 (784 bp sequence)


(SEQ ID No. 51)


11A


ATTTGCATGTCGCTATGTGTTCTGGGAAATCACCATAAACGTGAAATGTC


 


TTTGGATTTGGGAATCTTATAAGTTCTGTATGAGACCACTTTTTCCCATA


 


GGGCGGAGGGAAGCTCATCAGTGGGGCCACGAGCT6AGTGCGTCCTGTCA


 


CTCCACTCCCATGTCCCTTGGGAAGGTCTGAGACTAGGGCCAGAGGCGGC


 


CCTAACAGGGCTCTCCCTGAGCTTCGGGGAGGTGAGTTCCCAGAGAACGG


 


GGCTCCGCGCGAGGTCAGACTGGGCAGGAGATGCCGTGGACCCCGCCCTT


 


CGGGGAGGGGCCCGGCGGATGCCTCCTTTGCCGGAGCTTGGAACAGACTC


 


ACGGCCAGCGAAGTGAGTTCAATGGCTGAGGTGAGGTACCCCGCAGGGGA


 


CCTCATAACCCAATTCAGACTACTCTCCTCCGCCCATTTTTGGAAAAAAA


 


AAAAAAAAAAAAAAACAAAACGAAACCGGGCCGGGCGCGGTGGTTCACGC


 


CTATAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACAAGGTCAG


 


GAGGTCGAGACCATCCAGGCTAACACGGTGAAACCCCCCCCCATCTCTAC


 


TAAAAAAAAAAAATACAAAAAATTAGCCATTAGCCGGGCGTGGTGGCGGG


 


CGCCTATAATCCCAGCTACTTGGGAGGCTGAAGCAGAATGGCGTGAACCC


 


GGGAGGCGGAGCTTGCAGTGAGCCGAGATCGCGCCACTGCATTCCAGCCT


 


GGGCGACAGAGCGAGTCTCAAAAAAAAAAAAACC


 


Human Genome Map 2p24.3 (3000 bp sequence)


(SEQ ID No. 52)


12A


TGTATTTTAAATTATGATACATAATGACTATTTAACTTCCAAACAGAATT


 


CACTCATTTACATTTATGAACATTCTGGGTATAATATCCAGAGGGAATTA


 


AACCACTATCTCAGAGAGATATCTGCATTCTGATGTTCACTGAAACATTA


 


TTCACAGTAGCCAAAATACAGAAACAACCTGTCTGTCAACGAATTAATGG


 


ATAAATAAAAGAGATAAGGAATATATATATACACACACATACACACACAA


 


GCACACACACACACATACAATGGAAAATTATTCATCCTAAACGGAAATAA


 


AATTCTGCTATTTACAAGAAGAAGAATGAAACTGGAGGACCTTCTGCTTA


 


GAGAAATAAGTCAGACATAGAAAGACATATACTGCATGATCTGACTTGTA


 


TGTGGAATATAAAAAAGTAGAACTCATGAAAATAGAGTAGAAGGGTGGTT


 


ACCAGAAGTTATGGGGTGGGAGAAATGGAGAGCTATTGGTCCAAGGATGC


 


ACACTTTGAATCATAAGGAATAAGTTCTGGAGACCTGATGTGCAGTAGGA


 


TGACTATAGTTAATAATCATGTATTATATGCTTGAAATTTGCTAAGAGAA


 


TAGATATTCAGTATTCTTACAACACACACAGACACACACACACACAGGTA


 


TGTCAGGTGATGGATATGTCAATTAGCTTGATTGTGGTGATCATTTTTAT


 


AATATATACATATATCAAAATAGTATATTTCCAGTTTTTCACTTTTCTTT


 


TAATTTTTATTATCATATATTTTACTATATAAAATATTTTTAACTAACAT


 


GATGTCAGTCCAGCCTGACCAACATGGAGAAACCCCATCTCCACTAAAAA


 


TACAAAATTAGCTGGGCATGGTGGTGCATGCCTGTAATCCCAGCTACTGG


 


GGAGGCTGAGGCAGGAGAATCATTGGAACCTGGGAGGCGGAGTTTCTGGT


 


GAGCTGAGATCACACCATTGCACTCCAATCTGGGCAACAAAAGCAAAATT


 


CTGCCAAAAAAAAAAAATTCTGGACAGAATTTTGCATAGAAAGCCCTTTT


 


TCATCCCCAAATTATAATAATAACATAGTACATTTTCTTTTTGTAATTCC


 


AAGGGATCTATTTTTTGTTTATTTTGACATATAGCTCTTAGGTTCTTTTG


 


GCATTATTTAGTGTGTAAGAGTAAGTAAGGATATATTTTTATAGTTTTCC


 


AAATAATAGCAAATATCCAGAAATAACTTATAAAACAGGTCATCCTTTCA


 


CCATAAATGTGAAATGCTACCTTTATCCTATGTATTTGAATATATATACATAT


 


ATATTCAAGTACATTCTCTCTATATATGTGTGTTTATAATATCATATATA


 


TACACACACATATGTGTGTGTGTGTGTGTGTGTGTGTGTTACCTCTTTCA


 


ATTCCATAGTGTTTTAAGTAATCTAATTTTGGCATACTGAAAATACTGAT


 


AAGAAAAATTCTTATTTTTTCTTTCAAAATTTCCTTTGCATTTATAATAC


 


ATTAATTTTCCAGATAATCTTTAGAATCAGCTTATCAAACTTTGTTAGAA


 


GTGTATTTTATGTTAATCGAGACAATACTGGAGCTTGTAGAATAATTTCA


 


AGAAGAAAGACTCATCTAACATATTTGAGTATTTTCATGCAAGGGCAGAG


 


TATGTTTCTTCCTTTATTATTCTTTGCTCTCCTAAAGTAAAGATTTATAA


 


GTGGTTTATAATCCTTTTTTACTTTATATTAAGTTTATCTCTAGTTTTTT


 


ATAGTTTTTGCTATTATTATGGCTATAATTGTCTTTAATTGCTATTTTTA


 


ATTGAATGTTAATGTGTTAAAGGAAAACCATTAATTTTTGTATACTGATT


 


TGTGTCCTGTTAAGTTCATAAACTAGATTACTACTTCTAAAAGTTTTATT


 


TGATTGTTTTGACCTTTAGGTATAGAAAATCACATTGCTTGCACCTTACT


 


GCAAGTTCACAAATCCTTTCCATTACTTATACTTTGTAATTTTTTATCTG


 


TATTTAAATTAAGTAGTCCAGTGCAGTCAATATTGAATAAATGGTACTAG


 


TTATAGCAGGCCAGTTTTACTTTTATTATGAATTCTTACAGTATTATCAA


 


AGACGTTCTTTATCAAGTGAGGCAGTTTTTCCTATTTGCAGTTTGTCAAG


 


AGTACATTTTTAGTTTTACTATAAATTTGCGTTGAGTATTATCAAATGAC


 


TTCTTTCATATAGTGTCATTATCATGTATTTTCTCCTTTCACATTATCAA


 


GTAGAGAATTACATCAACAGTTGTCCTAATTCATATCATCCTGAACAAAT


 


TCTACTTAATCATGGCACACTAAATATGTAATTTTTTATAATAGTTTGGA


 


ATCTGAATTTATATTTTTGAATAAAATTTGTCGATAGTTTTTATTTTTCT


 


ATATGTGATTAATTTGCATTTTTGGAACAATGATTTTGCCAGGTTCATAG


 


ACTGAGTGAGAAAGGTCCATTAAAACTAGATTCATGTATTATTTGCTGAT


 


TAATAAATTAAATAACTTAGAAGTTATCTGTTAATAAATAGGTTACTAAA


 


ACTTGCCAGTGAAATTAGAGCTAAATTTTTATTTTTGTGTCAAGTATTTG


 


CCGAAATTCACTTTCTAAATTGTTATTGAACTATTTAAATTTTCTACCTA


 


TTCTTGAATCAAATTTTGTAATGTATATTTTTGTCAGTCTTACATGTTGT


 


TATAATTTTTAATATTATTTCATGCATTTGCATAAAATGTCACAAATTTC


 


TAAAATACGTTATGTTCCTGTAATTATGCTCATTATTTCATACTAACAAT


 


TTTCATTCTAGTACTCTTTTTTCCCCTTTCATCAGACTTAACAAAAGAGT


 


TGTCTATTTTATGAATCTTTGCAAATAAGTAGCCCTTGATTTTTATTTTT


 


AAGCCTATTTTTTATATGGAATTGTAATTGGAAGATTTAAAAAGTCAATA


 


TTGCACTGGAAAATATAAAATAAAAATTAATGTTTAATTCTATGTGT


 


Human Genome Map 3p12 (1921 bp sequence)


(SEQ ID No. 53)


14A


TTCTCTTTTCTCCACATCCTCACCAACATGTTATTTTTTGTCTGTTTAAT


 


AATAGCCATTCTAACTGATGTATGATTATATCTTATTTTGGTTTTAATTT


 


GCATTTTTCTGATTAGTAATGTTGAGCATTTTTAATATGCCTCTGGGCTA


 


TTTATATTTCTTCTTTTAAAAATGTCTATTCATGTTCTTTGCCGACTTTC


 


TAATGGATGATGGAATGCTAAAGGCCCAGACTTAACCACTATGCAATATA


 


GCCATGTAACAAAAGTGTACTTGTACCTCTTAAATTTATGCAAATAAAAA


 


CTCAAAAAAAAAAAAACAAAAAAACCTAAGATGACTAAATGTCAGAAAAC


 


CAGGTTTTACATGCCACTTCATTTGCTGAAATACAACGTACACAGCCTGT


 


TAAAATGAAGTCGTCTGCCCCCCAAAATATATAATATTAATAAGGTCTCT


 


ACCTAGAATCACCAGTTTACAATAAATGCAGAGGATAGATGCACATGTTA


 


GAAAACACCATAAAGGTGAAATCACCCAAAGTCTACTCGACAAATTATCC


 


AACTTCTTCAACCATTAAATAGCATAAAAGTTAGGGGAGGGGAATCTGTT


 


ACAGAACAAAGGAGATAATAATATATCATGCAAACACAAACCCATCTATA


 


TCTTGATTCAAATATAAATTGCAAAAAACGGCTTGAAATTACTATAGAAA


 


TTTCAACAGAAACAAGGTCTTAGATAAACAGTCCCCAACTTTTTTGGTAC


 


CAGGGACCAGTTTTGTGGGAGACAATTTGTCCACAGACAAAGGGTGGAGA


 


GGTGGGGATGGCTTCAGGATGAAACTGTTCCACCTTAAATCATCAGGCAT


 


TAGTTAGATTCTCAGAAGGAGTACACAACACAAATCCCTCACATGTGCAG


 


TTCACAATAGAGTTCATGCTCCTACGAGAATCTAATGCTGCTGCCCATCT


 


GACAGGAGGTAGAGCTCAGGCGGTAATGCTTGCTTGCCTGCCACTCACCT


 


CTTGCTGTGTGGCTCCGTTCATAACAGGCCACAGACTGGAACCCATCTGC


 


AGCCCCAGGGTTGGGGACCCCTGTCCTAGATAACATTTAGTAAATACAGT


 


TAATTCTTTTCAGTGCAATAACTTTGTTGAGATTGTTTTTTAACTGGCTA


 


GCCATATACAGAAAACAGAAACTGGACCCCTTCCTTACACCCTATACAAA


 


AATTAACTAATAAAAAAACACTGACATGTAAGACCTAAAACCATAAAAAC


 


CCTAGAAGAAAACCTGGGCCATACCATTCAGGACATAGGAAAGGACAAAG


 


GCTTCATGACAAAAACACCAAAAGCAAAGGCAACAAAAGCCAACATTGAC


 


AAATGAAATCTAATTAAACTAAAGAGATTCTGCACAGCAAAAGAAACTAT


 


CATCAGAGTGAACAGGCAACCTACAGAATGGGAGATAATTTTTGCCATAT


 


ATTCTTCTGACAAAGGGCTAATCTTTGTCAGAATCTACAAGGAACTTAAA


 


AAAATTTACAAGAAAAAAGCAACCCCATCAATAAGTGGGCAAAGGATGTG


 


AACAGACACTTCTCAAAAGAAGACATTTATGCAGCCAACAAACAAATGAA


 


AAAAAGCTCATCATCACAGGTCATTAGAAAAATGCAAATCAAAACTACAA


 


TGAGATACCATCTCACACCAGTTAGAACGGTGATCATTAAAAACTCAGGA


 


AACAACAGATGCTGGAGAGGACGTGGAGAAATAGGAACGCTTTTACACTG


 


CTGGTGGGAGTGTACATTAGTACAACCATTTTGGAAGACAGTGTGGCAAT


 


TCCTCAAGCATCTAGAACAGAAATACAATTTGACCCAGCCATCCCATTAC


 


TGGGTATATACCCAAAGGATTATAAACCATTCTACTATAAAGGCACATGC


 


ACACGTATGTTTATTGTGG


 


Human Genome Map 9q22-9q31 (2521 bp sequence)


(SEQ ID No. 54)


17A


TTTCAGCCTCCCTTCTACCCCACTCCAGGTACTTCTGCCTCTGTGGAATT


 


CCTGCTGATTCTAAGCCATGATGAGCATGGCTACCCTACCCTCTGATCTT


 


CCCTCCTACCGTGCTGGGCTCCTGTAGGAGGGGATCCCTCTCTTCCTCCT


 


CCACCAAATGTTGTCTCTTTTTGGAACCTTGTCTGAGCACTCTCCCCAGG


 


TGGGATGAGTCACTTCCTCCCTTTGTTCCCAGGCCCCTTTGTTCCTGTTT


 


CCCCTGAGAGGTCTCTGTCTTCTTCACCATGCTGGGAGTAACCTGAGGAC


 


AAGGTCAAGGCCGATGATGTCTATGAGCCCAAGAGAGGGTCTGGTGCGTA


 


AAAGCTGTTTGAGAGAGTATGCAGAAGGAATGGACAAATGAAAATTAGAG


 


ACTGACTTACAACTGGGGAAACTTCTCGTTGACCCTTTCTGTTCCTAAAG


 


AGAGTGTCACCGGATAGGGGTCAGGAGCCTGGGCTTTCAGTTGCAACAAG


 


AAGACTTCTTTGCTGTGGGCTTTCTGAAAGACAGTTCCTCTCTCTGTGAC


 


TCTTCAAAACAGACATGACAATCATGTGTGCCCTGCTTGCCCCTGAGGCT


 


GCGTTGAGAGATATAAAACCATCAGGAAAGTGCTCAGTGGCTGTGCACCT


 


GCAGCCAGCACCTCTGGCCAGTGTTGGAGAGCAAGGAAGGGAAAGCCAAG


 


GGAAGCCAATTCCTGGGAGCTTCTCCTGTCTGGGATGCCAAGGTGGAAAT


 


GAACTTGAGACCCAGACCAAACTTGAGGCTCTTTCATAGTCAGGTAATTT


 


GGGCACCCAGGGCATTGAGATCAGTCTGCCATTCACCCTGTGGCTAGCCA


 


CACCTACCTTCAGCTTTTTGACACTGGTACAGGGATCGTTGGAGAAGCTC


 


TCGGTGTCTGAAATCTCAATGTCCTCGCCATACAGAACTCCAGTCAGGTC


 


ATTCCGCACCTGTCAGCAAAGAGAAAGCAGAGGGTGGGTGTGCTGGGGAC


 


CACAGGAAGGGCCAGTTCCGAGGGGTCACCCTGGGGAAGTCAATTGGGCA


 


AAGCGATTTTCTCTACCGACAATGCAAAGTGAGTGGTTTTGTTTTACATT


 


ATTAACTAGACCGCCCCACAAAAACTTGAGGATCCCCCAGTCCCACCCTG


 


CAACTGACACATGGATACAAGGAGGCCAGACAGGGAAGGGACTTTCCAAG


 


ATTGCCCAGGGAGTTCCTGCAAGAGTCAAGATTAGCACCTTTGCTGGTGT


 


TTCTCCACCACATCACACTGTCTCCAAATCAGGCTATTCAATTGTGTCTT


 


TGTTAATATTTTGCACTATTTATTTGCAACATTATTTCACTTTTATGGTG


 


AGGAAATAGCTAAGATATTCAAAGACAATATAGAGTAAAGGAAAGAGGAA


 


AGAAGTATGGAACCTGCCTATGATGTTACACGTAACTATGTGTCTACTGA


 


CACTCAGAATGAGGAATATCTATGGATGTGAAAAGCAAAGGGCTGCAAAC


 


TCCAGTGTTACCAGGACCAGCCAGTGTGTGAACTAGCCTGTGTGGAAGGA


 


TATTACAGAATGATAGGGCTGGGCGTGGGCTCACACCTGTAATCCCAGAG


 


CTTTGGGAGGCCAAGACGGGGGGCTTGCTTGAGCCCAGGAGTTCAAGACT


 


GCAGTGAGCCGTGATCACGCCACCGTACTCCAGCCTGGGTGACAGAACAA


 


GACCTTGTCTCAACAGAACAAAACAAAACAAAAGACAGTAATAGTTGGTT


 


GCTGAGTTAGAATGTGGGTCAAGGGTTACCAGACCTTCTGATTTTTGAGG


 


GGAGAAATCAGAAATTTAGACTTTTAAAATATAAAATCCCCTAATTTTTA


 


AATGTTGATACTATTTTGAATTAAAAAAAAAAGAAAGTAAGGATCAAACC


 


AAATAAACTTAAAGTCTGTATCTGGCCTGTGGCCATGGCTGTGCACCCTC


 


TGACATATAGCAATGGAAACTGGATTTTGGGTTTTAGTAGCAAGAACTAG


 


GCTGGGGTTAGGGGATCCAGCTTCCAGGTCCTGCTCTATCACTGACTTGC


 


TTGTGACCTCAATCTCTCGTGTGATTCTTCCCTTCTCTGGGCCTCAGTTT


 


CTTCCGCTTTAGGAGATGCTTAAAGCACTTCTTGTTCACACCCATTAGCA


 


TGGCTATTACCAAAAAGCAAAACCACAAGTGTTGGTGAAGATGTGGAGAA


 


ACTGGAACCCTTGTGTGTTGCTGGTGGAAATGTAAAATGCTGCCACTGCT


 


GTGGAAAACAGTATAGCAGCCCCTCAAAAAAATAAATATAAAATTACCAC


 


ATGATCCAGCAATTCCACTTCTGGGCACGTACCCAAAAGAATTGGAAGCA


 


GGGACTTGACAGACATTTTACACCCATGTTCATAAGAACATTTGTTCACT


 


GCAGCTAAAAGGCAGAAGCAGCCCAAACGTTCACTGCTCGATGAATGGAT


 


AAATGAATTGTGGTGTATACAGACAGTGAAATACTATTCAGCCTTCAAAA


 


GGAATAAAATTCTGACACAT


 


Human Genome Map 3p12.3-12.2 (2641 bp sequence)


(SEQ ID No. 55)


19A


ACATATGATTTTTTCAAATTTTCTAAATAGTAATTATTTCCTAGCTCTGC


 


CTTCTGAAAAGTCCTAGAATTACAACAAGCTGGAAACAATGAACAAATGG


 


AGCCTTCAGACTGTAATCTCTAAATATGATTTTCCTTTTAGTGAAAAGAT


 


TTCTTTGGAGAAATAGTTGATTATAGATCTAGGTCAAGACATTTATGAGA


 


TGACCCTGGGACATTTTATTTTTGTCAGAAAGCCTGGAAAGTATTAATGT


 


GTCTACACAAAACAAAGGAACCAACTTAAAAGAGCAGTCACTGACCACAG


 


CAGAGATAATTGAAGCATCAAACTGAATAAAAAATATAACTCATTCAAGC


 


AGATGCAATTAGTTATCCTGAAAATGATAAATGCATGAATGTAATCAAAC


 


ATTAATACTTGGTTTCCTGTGCAATTCCTTTTCAGGGTAATGAAAACTGA


 


TGAGTGAGAGTTAAATGAAGGACTCCAGAAAGAATGACAGTTACAATATA


 


ATGATTTGTGCCCCCCAAATAAAATAATTGATCTACACAAAATACATCAG


 


TATTAGGCAAAACTAGATGGTAAAAAAATTTCGAAGAAAAATAGATTACG


 


GAGAACAAATCAGAACTCACTGATCAAACTTGATATGACTAATTTATAGT


 


TATTTGAGAAATCCACATGCTGTTTTCCATAGAGGTTGACTATTTTACAT


 


TCCAACTAATAATGTATAAGGCATTCTCTTTTCTCCACATCCTCACCAAC


 


ATGTTATTTTTTGTCTGTTTAATAATAGCCATTCTAACTGATGTATGATT


 


ATATCTTATTTTGGTTTTAATTTGCATTTTTCTGATTAGTAATGTTGAGC


 


ATTTTTAATATGCCTCTGGGCTATTTATATTTCTTCTTTTAAAAATGTCT


 


ATTCATGTTCTTTGCCGACTTTCTAATGGATGATGGAATGCTAAAGGCCC


 


AGACTTAACCACTATGCAATAGCCATGTAACAAAAGTGTACTTGTACCTC


 


TTAAATTTATGCAAATAAAAACTCAAAAAAAAAAAAACAAAAAAACCTAA


 


GATGACTAAATGTCAGAAAACCAGGTTTTACATGCCACTTCATTTGCTGA


 


AATACAACGTACACAGCCTGTTAAAATGAAGTCGTCTGCCCCCCAAAATA


 


TATAATATTAATAAGGTCTCTACCTAGAATCACCAGTTTACAATAAATGC


 


AGAGGATAGATGCACATGTTAGAAAACACCATAAAGGTGAAATCACCCAA


 


AGTCTACTCGACAAATTATCCAACTTCTTCAACCATTAAATAGCATAAAA


 


GTTAGGGGAGGGGAATCTGTTACAGAACAAAGGAGATAATAATATATCAT


 


GCAACACAAACCCATCTATATCTTGATTCAAATATCAATTGCAAACGGCT


 


TGAAATACTATAGAAATTTGAACAGAAACAAGGTCTTAGATAAACAGTCC


 


CCAACTTTTTTGGTACCAGGGACCAGTTTTGTGGGAGACAATTTGTCCAC


 


AGACAAAGGGTGGAGAGGTGGGGATGGCTTCAGGATGAAACTGTTCCACC


 


TTAAATCATCAGGCATTAGTTAGATTCTCAGAAGGAGTACACAACACAAA


 


TCCCTCACATGTGCAGTTCACAATAGAGTTCATGCTCCTACGAGAATCTA


 


ATGCTGCTGCCCATCTGACAGGAGGTAGAGCTCAGGCGGTAATGCTTGCT


 


TGCCTGCCACTCACCTCTTGCTGTGTGGCTCCGTTCATAACAGGCCACAG


 


ACTGGAACCCATCTGCAGCCCCAGGGTTGGGGACCCCTGTCCTAGATAAC


 


ATTTAGTAAATACAGTTAATTCTTTTCAGTGCAATAACTTTGTTGAGATT


 


GTTTTTTAACTGGCTAGCCATATACAGAAAACAGAAACTGGACCCCTTCC


 


TTACACCCTATACAAAAATTAACTAATAAAAAAACACTGACATGTAAGAC


 


CTAAAACCATAAAAACCCTAGAAGAAAACCTGGGCCATACCATTCAGGAC


 


ATAGGAAAGGACAAAGGCTTCATGACAAAAACACCAAAAGCAAAGGCAAC


 


AAAGCCAACATTGACAAATGAAATCTAATTAACTAAAGAGATTCTGCACA


 


GCAAAAGAAACTATCATCAGAGTGAACAGGCAACCTACAGAATGGGAGAT


 


AATTTTTGCCATATATTCTTCTGACAAAGGGCTAATATCCAGAATCTACA


 


AGGAACTTAAAAAAATTTACAAGAAAAAAGCAACCCCATCAATAAGTGGG


 


CAAAGGATGTGAACAGACACTTCTCAAAAGAAGACATTTATGCAGCCAAC


 


AAACAAATGAAAAAAAGCTCATCATCACAGGTCATTAGAAAAATGCAAAT


 


CAAAACTACAATGAGATACCATCTCACACCAGTTAGAACGGTGATCATTA


 


AAAACTCAGGAAACAACAGATGCTGGAGAGGACGTGGAGAAATAGGAACG


 


CTTTTACACTGCTGGTGGGAGTGTACATTAGTACAACCATTTTGGAAGAC


 


AGTGTGGCAATTCCTCAAGCATCTAGAAGCAGAAATACAATTTGACCCAG


 


CCATCCCATTACTGGGTATATACCCAAAGGATTATAAACCATTCTACTAT


 


AAAGGCACATGCACACGTATGTTTATTGTGG


 


Human Genonie Map 14q22.1 (2341 bp sequence)


(SEQ ID No. 56)


20A


AGGCCTCAGTGTCCTAGACTAGCACAGAACAAGCAGATGAAACAAAGTTT


 


ATATCAGAATGTCAACTGAAAAAGTATCATTTACCATAAATGGAAGATAA


 


TTGTATTAAATTCTAGTTAGATGCTAAAACTTCAAGAACTTTTAGAGTCT


 


GTACCTGCATTCTGTTAAAAATATAGATTAAAAAATGCTAACATGTTAAC


 


ACAAAGGACTTTCCAGAAAGACTTAAAGAAAAGTGAAGGGGAATAACTGT


 


CTTGCAATGTAATTCATTGTCGTTTAAGACTGGGTCTATGGAACACCCTA


 


AATCACCTGGTTCCATCACGTTCTTTTTAACATGGAGATGGATAGTTTTT


 


CCCCATACTCTATATATTGAGCATTCTATAGTTCATGATTTTTCTGCATA


 


GAGAATTGTTCAAGCCGGGGGTGCAGGCTCACCGACTGGATAGTGAATCA


 


AGAAAATAGTGTGTTCATTAGTTCATCATTACCCTGAGTTTCCAACAAGA


 


ATTTAGTACAGGAAAGTAGACAGCGGAGCTGGGAGCCATCTATTTGAAAC


 


TGTCTTAAGCAAACTAAGAAACCGAGTAAGCTTGCTTTTGGTGTCTTTCA


 


TCCCTTCTTGTGTGCCCCCTAATTATTCACTCCCCAATGCCCAGACATTA


 


TGATGCCTTCTCCTGCTCAGAGACCTTTCTGGGAGGAAGACCTACTCAGA


 


CCTGGTATTCCCTCATCCTAGGCTCTACCCTATTTTTCATCCAGCTGTTA


 


AAGCTGAGTGACTAATTTCACACTTATGTACGAATGACCCATAACTGGCT


 


TAATGCTGTGACCATCTTGGGGGTATTCAAAGCTGATAAACACTTTTTTA


 


AGTTATATAATAATCAAAGAAGCTTATCTTTCTGCTTTATTTCAAATTTC


 


ACCCCACAGGCCTTACTTATTTTTAAGATCAATGATTTTGATGGGCCCCC


 


CCTTCCCACTCTTAATTCAGGGTATTTCTGGCCCCATCCGGATCCAAACT


 


CTAATGCTCATCTCTTCCATACTGTCCTTTGCAGGTCATCGGTATTGCAA


 


GAGTTGCATAAGGCCCAATTCAGTCTCTGCCCCAAAAGCTCAAGTCCAAA


 


CTTCAGAATCTGGGAGGACAAGGATTCAGGAAATTTTGTCAGAACTATGA


 


CTTTGAACTTTCACTTTTATGGTGAGGGTCACATTTGGTCTGAATCAATT


 


AATCCATTACCCGCCCCCCCCCCCCCCCCCACCACCACCATGTGTGAATT


 


CAAAATAATCAACTTGGGTTTATTATAAAAAACAAAATATATTAATATAA


 


GTATACTAAGATTTTTCTAGAAAACTTGGCCGGGCGCGGTGGCTCACGCC


 


TGTAATCCCAGCACTTTGGGAGACCGAGGAGGGCGGATCACAAGGTCAGG


 


AGATCGAGACCATCCTGGCTAACACGGTGAAACCCCATCTGTACTAAAAA


 


TACAAAAAATTAGCCGGGCGTGGTGGCGGGCGCCTGTAGTCCCAGCTACT


 


CGGGAGGCTGAGGCGGGAGAATGGCGTGAACCCGGGAGGCGGAGCTTGCA


 


GTGAGCCCAGATCGCGCCACTGCACTCTGCCTGGGTAACAGAGTGAGACC


 


CTGTCTCAAAAAACAACAAACAAATAAACTTAGAAGAATATATGTGACTA


 


TTGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCCCTTTGGGAGGCC


 


GAGGCGGGCAGATCACGAGGTCAGGAGATAGAGACCATCCTGGCTAACAT


 


GGTGAAACCCTGTCTCTACTAAAAATAAAAAAATAAAAAATAAAAAATGC


 


GAGGTGGCGGGCGCCTGTAGTCCCAGCTATTCAGGAGGCTGAAGCAGGAG


 


AATGGCGTGAACCCGGGAGGCGGAGCTTGCAGTGAGCCGAGATCGCGCCA


 


CTGCACTCCAGCCTGGGCAACAGAGTGAGACTCCGTCTCAAAAAAAAAAA


 


AAAAAGAAGAAGAAGAAAGAAAAAGAAAAGAAAAAGGAAAAAGAAAACTT


 


AATTCTGGCAATGGACTGTTTCTAAAATAATATATTAATACTACTTAATG


 


AGGAAGAAAAAACCTCTGACATCCTAAAATGCCAAGTGTTTGCCTTTACC


 


AAGGTTTAAGCACACATAAACACGCATATTCAAATACCACCCAAAGTGGA


 


GGTGCAAAGATCAGCCTGTACCGCACAGTAACACAGACTGGGTTGTTTTT


 


TGTAAAGAAGGCAACTAGTCCAGTGAGTAATCCCTTCATTTTCCACACAC


 


ATACCCTTCTGTTTTCTCCCTCTCCTCCCCCCACACCCTCCACTGCAGTT


 


AAAACGTAATTCGAAGAAGCCTAAGGTAAAAGCCCCT


 


Human Genome Map 8q24.13 (2100 bp sequence)


(SEQ ID No. 57)


GTGGACAGGGAAATCTTACCTTCCTGCCTCTCTATGTTCAGGCTGAGTGG


 


GTCAGAAGGAGAGTGTATTAGGTAAGAAAATTTATCAGTATTATTTAGTG


 


AACACTGGATTTATCCTTTTGCATTCTGGCTGTAGTACCCAACTTCCACA


 


TGGCAATGCACCCTCACCTCAGCCCTCCGCCCACGTGGTCCCCTTGCTGA


 


GCACTTTAATGAATGACTGCATCTCATTTTCACAGCTATTTGATGCACCT


 


GCTATTATTACTCTTATTACCATTTTCCAGTGGGAAGCTGCTTCTTGGGC


 


AGGGTGGATTTCCATCTGCGTCTCCTTTTCGGTGTTGAAAGCTGGTAAGT


 


GAGGACACCAGGATTGGAACCTGGGTAGTCTGAGTCCAGAATCTCTATTT


 


TCAAGTCTTCCTGCTCTCTGCTTCTGGCAAGTTTGATGTCCACTTTTGAT


 


CTTCACCTACATTCCAGCATAATAGCTACTTTTGGTTGTTTTCTCAGCAG


 


CACAAGAGAAGTGTGGCGAGATTTTTAGGTGAGTCATCTAGAGAAGTTAA


 


TCTTATTTTGGGAATTCTACTGGCAGCTTCAGGTGGGGAAAATTTTGTTA


 


TTTTCTATCCTCCTCTAGGTTCTAAAAGGGAAGAAAGATGGTGAGCGTAG


 


AAAGATGTGACTGTATTCACTATTCACCCTTTGTCGGGTGGTGAGTAAGC


 


AGCTTGCAAAGATGCAATGAAGTTTGGAACAATCCAGAGAACCAAACTTT


 


CAGCTGCCAGAGATGGCACCTGGTATCCTGGGTACATCTGCCTGTAGGGC


 


CCAGAAAGAGCTGGAAGCCAAGTGCATGGATCAGGTCTGTAGGAAGGTGG


 


GAGAGCCAGGAATCGAGTGTCAGGGGGCATTTATTACCCATGGAAGCAGG


 


TTTTTGTCAATTTTGTTCACTGCTGGATCACTAACACCTGGACTGGTGCC


 


TGGCCAGGTGGTGGCTTCATAATCATTTGTTGAGTGAATCAATGAATGAA


 


TGAATGAACAGCTGTAGCAGATGCTAGCAGGGCTTCCTATTTCTTCCATC


 


ACCATAAAGGTGAAAGACATCATAAACGGGAATTTAGACAATCCTCAGAA


 


ATTTTCAACTGCCATGTATCTTGACTTGATGCTTCTAGTAGTTATATTTA


 


TTTGTAATTCAATCTTTCTTTTTAAATAGTTGACCAAGTGTGGTGGCTCA


 


CGTAGTCCCAGCACTTTGGGAGGCTGAGGCAGGAGGATCACTTGAGCCCA


 


GGAATTTGAGACCAGCTTGGGCAACATAGTGAGACCTCATCTCTTAAAAA


 


AAAAAATTAGCTGGGTGTGGTAGTGCACACCTGTGGTCCCAGCTACTTTA


 


GAGGCTGAGGTAGAGGATTGCTTGAGCCTGGGAAGTTGGGGCTGTAGTGA


 


GCTTTGATTGCATCACTGCACTCCAGCCTGGGTGACAGAGCAAGACCCTG


 


TCTCTAAAAAATTAAATAAATAATAAAAAAATTAAAAAGTAACTCCCTTT


 


TCTTTATTTTCAGGCTTCCTTCCCACCTGCTAATTCAAACACTTTACAAC


 


CAAAAATATCTTACCTTGATCCTGTTTCTTTCTCTATAACCTCTCTATTT


 


CTGTTTCTTTCAACCAAATTTCTTAGGTCATCTATAATTTTGTTTCTACT


 


TTTTCTATGCATGCCTCAATCCATTGCCAACTCCTCAACCTGCCCCAAGT


 


GCCCACAACTCCACCAAAAGTAATTCTAACATTTTACCAATCCAATACAT


 


CACAGTTTTTTATAAAAAACTTAAGAAATATACTTTAGTTGAATTTGAAA


 


GAGTTGCCCACTTGTGTTAAATATTTCTTTCCTTGTGTCTGGGATATCAT


 


TTGATTCTGATTCTATTCCTAATTCTCTGACCACCCTTTCTTCGTAGATT


 


TCTCTTCCTTTGTTCAGCCTTTCACATCCTTGGAGTTCCATCCTCTGGTG


 


ATTGTTTGTCCTGTTCCATACATTCTCCTTATATGAGCATTGTGTTTTAG


 


CTTATGAATGGTCACATGACCTAGCCAGGCCAATCAGAGTCTTCCATGAG


 


ACTTTTGTTTATTTATTTATTTATTAATTTATTTATTCTTCCACATGCCA


 


TC


 


Human Genome Map 6q16-q21 (2100 bp sequence)


(SEQ ID No. 58)


22A


GCACACCTGAGCAAGGGAGAGGAAAGGGTTCTTATTCCTGACACAGGTAG


 


CCCCTACTGTTGTGTTGTTCCCCTGTTGGCTAGGGCTGGAACGCACAGTC


 


AAAGCTAATTCCGATTGGCTATTTTAAAGAGAGCAGGCGTAGGAGCCAGA


 


ATGGTGGGGCGAGTAGTTTGGCGGGAAGGTCAGTTACAGAACAGGTGACT


 


CAGGATGACTCAGGTCAGAGCAGGTGACCAGGGGTGTCTCAGGATGGAGC


 


AGGTGACCAGGGGTGACACAGGATGGAGCAGGTGATAGAGGCTAGGAGGG


 


GGTTGTTTACTGAAACTAGGGGCAAGGAGATGACGAGAACGAGAAAGTTA


 


AACTTTAAAATGAAGAACAAAGAACAGGGGAGCTGAACATACTGATAGAA


 


CTCTTTCAAGTCTACTTAGGTAACTATTTGTTTGTTTTTCTGCTTCTAAA


 


ATTTTGTTGAAATTTTCTCCTTTCTTATTCTCATTGTTCTTGAGGTTTCG


 


TGTATTTAAAAAATCTTCTTACTCTGTAATTGTCATAGTTGAGTAGGGAG


 


CAACGTTAGATTAATATATTCAATACTTCACTGTTACCTGGAATAAGAGC


 


CCTCTCTTTAAACAAAATATTATGCAGAAATCTAATACAGGAAGCAAATA


 


AAAACTAGAACTACTCTGGTTCAAATAGAGTGAAGACAGAGCAGATCTTG


 


TTCTTGTAATTGAAAGGAATATGATATAATAAGTATTGACAATATTTTCT


 


TCTCACCAAATAAGTTTCTAATTCTATATATAAAGGAAATACTTTCAGAA


 


TAAAACGAATATATGAGTTTTATTTTTAAATCACAAAACGAAGTTCAAGA


 


ACATTTTTGAAACTGGGAAGATTCATATTTTAGTATCTGTCAAATGATGA


 


TAAATTCGGAAGCCAGTGTAATTTATACCCTAGGGGCTGAGGTCTAATTC


 


AACATATTCCAGTTTCTATTTTCTAAAGCTAAAGAAACATGTGTTACAAT


 


GTAGATAGGGAATACTTTCTTAATGAACCATGCTGAACTGTAAGATTTTT


 


AAGACTCCTTTTTAATGCATTACATTACACTGTATCTTGTTTTCACATTT


 


ATGGTGAGGTTAATATAAAGAGACATTAAACAAATATATTTCTGCTCTTT


 


ACAAAGGATGATTATTGTTTTCTTACATTTCAACTAAAAATTTCTATAAT


 


ATTATACTTGCAAGAAGTATAACACTCTTAATGAGCAATACAGTTAACCT


 


TAAGGTTAACTTGCAAAATTTCATGTCTAATTTAGTATCATTAACACATT


 


GAAAAATCTCTCCTAAATTTCACTCATCTTGATCAAAATCCATGTTAAAG


 


GTTTTGAAACTACACTTAATACATCTGCCTTATTTTATGCCCCCACTTAT


 


ACTACTAGTTATTAATGCACTTTGGACAGCTGGTTCCTCTGCCTTTTGAG


 


GATTCTGTGGTGTAACTGATTGGTTCTCAGCTTTTTCCACTGCCCATTTG


 


GGATGCAACCCTTTCAAGTCTGCTTAGGTAACTATAATTTGTTCATGTGT


 


TTTTCTACTTCTAAAATTTGGCTGACATTTTCTCCTTATTCTTGTTGTTC


 


TTGAGGTTTTATGCACTTAAAAAATCTTTCTACTGTAATTATCGTAGTTG


 


AGTAGGGAGCAACATTAGATTCATGTATTCAATACTTCACTGTTACCTGG


 


AATAAGAGCCTTTTTTAAGGGCTCTTACTGAAAAACACAATACACTTATG


 


TTCTTCTATAATGTTTTAAGGAATTTTTTAACATTAATCTCCTGTCTCAG


 


CCTTTAAGGCCATTAAATGACTTAAGATAGTTGCTGTGGCTCCAAACATT


 


GTATCCACATTTCCACAAGAGGAAGTAAAAAAAGAAAAAAATGAGTCTTG


 


CCCTTTCCTTGTAAAGACAATTTCCACAAGGTTCACATTCCTCTGGTCAG


 


AAATCAGTCATACACCCACGCCTAGCTGGAAGGTAGGTTGGGTAATGTGG


 


ACTTTAATTCAGACAGTATTGTGTCAGTAAAAGTCAGGGGTTCTATTATT


 


AGAAGCAGTGTAAACAGACATGAGAAAACAAACTGTAGCCTCTGTGCTT


 


Human Genome Map Xq21.3 (2160 bp sequence)


(SEQ ID No. 59)


23A


TAAATATAAATAAATCATCACTAGGTATGTTCTAATAAAATTTCAGAACA


 


CCAAAGATGAAGATAAATTTTAAAAGTAGCCAGAGGAAAAAGGTGAATTA


 


CCTTTAAAAGGTTACAGTTTAACAAGAAGTCTGACTTTTCAACTACAAAG


 


ATTTTCAGAATAATATCTTCAGTATGCTGAATGAAGTTTTAAAAAGCAGC


 


TGCCAAAAGAGTTTTAAACTGTGTAGGTATATTTCAAGACTAAAGGGAAA


 


TGAAAACATCTGTAGATAATGAAATCTGTAATTACCAACTGAACTTAAGG


 


ATATGCTTCAAGTGGAAGAAAAGTTAATTGAAATGGAGGGTCTGAGATGT


 


AAGACAGAATGAGAAATAAATAAAATAGCAAATATATAAATAAATCTAGA


 


TGAACACTGACTGCAAAAAGCTACAATAATGATAACATCTTTGGGCATTT


 


AAAAAGATAATTAAAATAAGTAAGAGGAGTGACAAATTCTTTGGGAGGTG


 


ATTAAATTGAATGAAAGTATTCTAAGGTACTTGCACAGTCACAAGGGGTG


 


AAAAAAGGTTTTGTTTATAGTAAGACTTTGTCAAGTAGGCATATGTAATT


 


TCCAGGTTACCCATAAAAAATTCAAAACAGAAAGTGAAATTTCCAAATTA


 


GTAGAGAAAAAAGTGACATAATAAAAATTATTCAATTCAAAATGAGGCAA


 


AAAAGAAGAGACAAAGAAACACGGGATATTTAGTACAAATAAAAATCACA


 


ACATAATACAGTTCATTAAAACTCAAATTTGTTAGTAATTCCATTGATTA


 


TATATGAATTATGTGTTCCATTTATGAAGCAAAATATCAGAAGAAAAATC


 


CACCCATATACTGTTTTAAAGAAACATTTAAGACATAAGAATACAGAAAG


 


TTTGGCAGTAAATGAATCAAAAATGAAATAATGAGTCTACGTGAGGATAA


 


TCAATGTTCACTGAAATATTAGGGTGAAATGCTGATGGAGAACTTTATAA


 


TAGATATACCAGGTCTATAACACCTGAGCCTAATCAAATGTAACACCATA


 


AAAGTGAAATATCCAGACGCTATCCACCAGATTATAGGAAATGCAAAGCA


 


AAAGAATATTAAAAGACATAAAGATGACTCAATCTTGCAATTCCAGAACA


 


TGGGAACTTCTAAAAGATAAATTGTTTTAATCAATATGTAGTAAAAAGGG


 


AAAGGGAACTGTTATTGAATAAAAGTGACATCGTGACCAAATGTAATGTA


 


ATAACTTTGGACACTGCTTGAAGAAACCAACTATAAAAATTCATATTGAG


 


TCAGTCAAGAACATGTTTATATTGACTGGAATTTTATTACTTTAAGGATT


 


AGTATTAATTTTTCAGTGTAGTAATGGATTGTAGTTATAGTAAAAAAAAG


 


TTCTTATTTTTGAAATTTACATTGAATTATTGATGAATAAAATTATGTGA


 


TATTTGGAATTTTCTTTAACATAATTTTCATTATTAATAATAAAATCATG


 


AAAAGGAACAACTCTTGTTGAATGCACATTGGAACTCTGTTGAAGCAGGC


 


ATTTCTGACCTAGGGGGAAAAAAAACATAAAAGAGAAGATTTTTATGTGA


 


TAAATACAGGTGGTTGCCAGGGGCTGCCGGGTGGGGAAAATGGGGAGATG


 


TTAGTCAAATGGTACAAAGTTTCAGTTGTGCAGGATGAGTAAATAAGCTC


 


TGGAGATCCAGTGTACAACATGATGACTATAGTTAATAATACTGTATTAT


 


ATACTTAAAATTTTCTGAGTAGGTTTGAAACGTTCTCGCCATACACACAC


 


AGAAAAGGGTAACTGTGAGGTGATGAATACGTATTCAAGCTAATCACGTA


 


ATTAGCTCGATTGTGGTATTTATTTCACAATGTATAAGTAAATTAATAAA


 


TCACATTGTACTCAACTATAWATATTTTTTGTCAATTATACCTCAATAAA


 


GCTGGGGAAAATGTAAAATAAATAAATAAATTACCGAAAAJ4ACCCAAAC


 


ATCCATAAATGAAAATGATACCAAATCTGGCGCCACTTTTTACAATGGAT


 


GTAAAAGTCAAGAGTTAAAATCTTTAACATGCATGCTTACTATGTCGAAA


 


GATCACGTACATGAAAACAAACATACTTTATTGTGATTTTTTTGAATGTA


 


AGCGATGAA


 


Human Genome Map 12q21 (2219 bp sequence)


(SEQ ID No. 60)


24A


TATAATTATTAACTGAAGTCATAGTTTACATTAAGGCTTACACTTTGTGT


 


TGAATAGTTCTATGGATGAGGGAAGGGGCTAAAATGCATAATTTTATGCA


 


TTCACCATTAAATATCATGGGGAATAGTTTTACTGTCTTAAAAATTTCCT


 


TCATTTCAATTATTTGTTCTTCTCTCCACTCTCTAAAGCCCTGGAAACCA


 


CTTATCATTTTATTGTCTCTATATTTCTGTCTTTTTCAGAGCGTCATGTA


 


GCTGGACTTATACAGCAAGTAGCCTCTTCAGATTGGCTTCTTTAACTTAG


 


TAATATTCATGTAACATTGCTCCATGTGTTTTCGTGGCTTAATAGGTCAT


 


TCCTTTTCATTACTGATCATTTTATTCTGTGCATGTACCACAATTTGTTC


 


GTCTACTACTGAATGATGTCTTGATTGTTTCGGTTGTTGGTGATTATGAA


 


TAAACTTGCTATAAACATTTACTTGTGTGGATGTAAGTTTTCAACTTATT


 


CAGATAATATTTAAAAGAGCAATTGCTGTATAGTATGGTAAGATTATGTT


 


TAGCCTTGTATGGAACTGCCAAAGTGGCTGTACCATTTTGTATTCCTACC


 


AGCAATGAATGAAAACACCTGTTGATCTGCATCCTTACCACTATATGATA


 


TTGTCATATTTCAGATTTTAATCCGTCTAATAGATGTGTAGTGGTAGATA


 


GTTGCTTAATTTTCAATTCTCTTATGACATACAATGTTTAACATCTTTTT


 


ATATGTATATTTGCTATCTGTATATCCTCTTTGGTGAGGTGTCTGTTCAG


 


ATCTTTTTCCCATTTTAAATTGGATTGTTTTCTTATTTTTGAGTTTTAAG


 


TGTTCTTTTTATATTTTAAGTGCAAGCCCTTTATCAGATATGTATTTTGT


 


GCATATTTTCCCACTCTGTGGCTTGTATTTTAATTCTCTTAATAATATCT


 


TTGCAGAAGTTTTTAATTTGAACAAATTTCACTTTTATGGTGTGCTTAAG


 


AAGTTGTATCTAAAAACACAAGGTCACCTATATTTTCTCCTGTTACAGAA


 


GTTTTAGACTGTGGGTTTTTTATTTAGCTCTATGATCCATTTTGAGCTAA


 


TTTTTGTGAACTGTGTAAAGTCTATGTCTGGATTCTTTTTTTTTCCAATG


 


TAGATATCCAGTTGTTCCAGCATCACTTGTTGAAAAGATTATCTTTTCTA


 


CAGTGAATTGCATTTGTTTCTTTGTCTAAGATCAGTTTACTATATTTGTG


 


TGGGTCTATTTCTAGGCTCTCTATTCTGTTCTATTGGTCTATGTGTTAAT


 


TCTTCCATAACATGCTGTTTTGACTATTGCAGCTTTATAGTAAATTTTCC


 


ATTTGAATTGTGTCATATTCTTCTTTGTTCTTCTTCTTGTGTATTATGTT


 


GCCTATTCTGAGTCTTTTTGTATTTTAATATAAACTTTCTTGTCAATTTG


 


TTGATACACAGAAATAACTTGCTTGGATTTTAATGGGAGTTGCAATGAAT


 


GTGGAAATTAAGTTGAGAAGAATTGACATCTTAGCAATATAGAGTCTTTC


 


CTGTCCCTATACATAGAATATCTATCTAGATCTTCTTTGATCTCCTTCAT


 


CAGACTTTTGTAGTTTTAGCCACATAGATCCTGTACATATTTTGTTTGAT


 


CTATACTTAAATATTTTATGTAATCAATTGACTTTTGTATATTAACTTTT


 


TATCCTACAACCTTGCTATAACAGCTTATTAGTTTCAGGGACTTTTTGCC


 


AACTATGGGATTTTCTGCATATAAATCATGCAAAATATGCAATCATGTCA


 


TCACCAAACAAATATAGTTCTATCTATGCCTTCCCAATATGTACACCCTT


 


TATTTCTTTTTCTTGTCTTATTGCATTGGCCAGGCCTTCCAGTACAATGT


 


TGAAAAGGAATGGTGAGATACAATATTCTTGCCTCTTTTTTCATTTTACG


 


AGGAAAGCATTCCTTTTAATAGTAGGCAGTCAGAATATAATATGTAATAT


 


TTTTAAAGGCAATAAATAGACATCTAAGTGAGTTATTTTAAAATTGAGAG


 


TTTAAAATCAAATAAAACTAAAAGAATTTAATAGTTTGCCTCTGTATCAT


 


GGAATGAAGGAGTTAACAAGAGCTGATGAGAGAATCTGCTATTTGTCACT


 


ATATCTTTTATTAGCATTTGACTTTTAAATATGTTACAATGAATATTTTA


 


ATAATTTTCTTCATAA


 


Human Genome Map 7q22 (2160 bp sequence)


(SEQ ID No. 61)


27A


ACATCTGTCTGTTTTGTGTGGCCGTCACAAAATAATCAAAGACTAAGTAA


 


TTTATAAAGAACAAAAATTTATTTCTCATAGTTAATGGAGGCTGAGAAGT


 


CCAAGACGAAAGTGCTGGCATCTCATGAGGGTCTTCTTCCTGTGTCCCCA


 


CAGGGCATAAGAGTGTAAGACTATGAACTCATTTCTGCAAGCCCTTTATA


 


CAATGATGTTAATTCATTCATGAGAGTGGGGACCTCGTGACCTAAACACC


 


TCCCATTAGATTCTACCTCCCAACACTGTTGCACTGTGCATTGAGTTTCT


 


AACACATAAATTTTGGGGGGCACATTCAAACCATAACATGGAGTTTTCTG


 


CATTGAGAAATGAAGGATCCATTTAATACAGGGACCTCAAAATACAAAGA


 


GAAAACTGACTGGCTGTATGGAGCTAGACGAAGAGGAGTAAGAAACTACT


 


ATTTGCAAGGCTGTGTAATTCCAAGGACTGTTATTCTTGGATGCTATGAT


 


GTTTTTAAAGAACAJACTACTATACATTTGTAAGTTATTAAATTATTAAT


 


ATTATTTGAGAATTTCAAATGGCTTAACTAATCAATGTGACATAGTGGGA


 


AAATTGGGCCTTTAATTGAAGACACAATTTGCTGATTACCACTTGGTAAC


 


TTAGCCCTTGCTTCTCTAACCCTTAGTTCATCTTGTAAAATGCATTAGTT


 


CTACTCCATAGGGGTATTGTGAGATTTAAACGCAGTGCAGCATATTAAGC


 


ACCCAGTGTAGTCCCTGATACATAGTGAAACATCAATAATAAATTGTTGC


 


TACTGGTAGAAATCCCTTGGCGTTTGGTAGATTTCCAATAAATACTAATT


 


CTTCTAAAACTTTTAATGATTATGTAGATAGATATATGCCTAGATCTGGT


 


AACAAATATGCTATATCAATAGTCAAAACATTCTCTCTTAATTTTATTAT


 


GATATATATTGGAAATCTTAGTGTGGTTTTGATTATACTAACATAATTAT


 


GTGGCATTAGTATGCCAAATGTACTCACAGTTATGCCAAAATTACCTGCC


 


CCAAATTACAGCTAATCCTTTCTTTGGTCCTAGGAGAGATACGCACACTA


 


GGGATATCACCATAAAAGTGAAGAAACACTTTATTACTGGCTGGGCTTGT


 


TTCTGAAATTCTAACACAGAGTTCTTATAACATGGACTTTTCCTTGCCTC


 


CTAGTTCAAGCTTGAGGGCTTACTGTGCTCTTGCAGGGAAAGATAAAAGA


 


AAGTGTCAGAGTGAAAGAATGGTCAAATGTATGAACTCTTCTTTTATTTA


 


TTAATTTAAATACAGTGACTCTGTTCACTAGTAAACACACCTAACCCCTG


 


CCTTAGAGTCAGATTAACATCTTCTTTGAGGACAGCCCAAAGAAGAAAAA


 


TGCAAGGATGAAGCCTAGAGAGGTTTCCATCTCGTATACTTATATTCCAC


 


TATCTTTGGTTCTTTCTTTCAACCATTAGACTTAAACCCAACTGTATAAT


 


TAATCAAACATGTGGATATTTCCTTGGAGGAAGAAATAGAGAAGTGTCAG


 


GGAAGTTCGACCGCCACCTAAGTGTGTCTGCTTTTTTAATGCTGCCTTAT


 


GGTCTAAAGAGATGGGTGAAAAGCAGAGTATTCATTTCAAGGCCATACTA


 


TATTATATGCCATCTATTCACTCCAGGCTGCTTGTTGTCAAGGAAGAATA


 


AAAACCTTGATATCAAAGAGAATTAAGCTCTCAAAATTAGTTTCTCTTTC


 


ACATACCAAAGTAACCTTGAGCTTTCTAGCCTGCAAATTTCTCTCCCTTA


 


ATATTCTTTCTCTGTTCCGTTCCACTGAAAGTGATGTCACAGTGGTGTAG


 


TTAGAGTCTGGGTTACTCTTTCCTGCAGAACTGTTCTTCAGTACCTCTAG


 


ATAGAAAATAGTCCAACATCAAGTCTTGCATGAGTTTTCCTTTACCAAAG


 


ATCTAGTAGTCTAGAAGATATTTAAAAATCACATTATTGAGCCCACATCT


 


GCAAAAAGGAGAAGTATATACAATATTCTTAGGACTCAATACATATTACT


 


TGTGTGCTTGTCTTTGCATGGACATGTATGTGTTTTAATTTCTCTTGCGT


 


AAACACTTAGGGTTGGCATTGCTGACCCACATGGTAAGTGTATGTTTAAC


 


TTTATAAGCA


 


Human genome Map 11p15 (2160 bp sequence)


(SEQ ID No. 62)


29A


TACTGCTTCATCCTTGAGTTCTACAAAACACACACACACAAAAACCAACA


 


AAACTTAACTATAGGCTGGGTGAAGTGGCTCATGCCTGTAATCCCAGTGC


 


TGTGGGAAGATCTTTTGAAGCTAGGAGGTTTAATCAGCCTGGGCATCAAG


 


GCAAGACCCCATCTCTACAAAAAAAAAAAAAAGCCAGGCATGGTAGTGCA


 


CACCTGCAGTCCTAGCTACTCAGAAGGCTGAGGTAGGAGGATCACTTGAA


 


CCCAGCAGTTTGAGATTGCAGTAAGCCATGATCACATTACTGCACTCCAG


 


CCTGGCTGACAGAACAAAACACCACCTCTAAAAATAAAAATATAAAATAA


 


ATAAAAAAATTTAAAAACCTAAACATAGCTGCACTTTACTCAATATATTT


 


ACAGTTCTACATATGTAAAAACTTGTATATTGACTATGTTTTAAATGTGT


 


AGGGGAAGTTTCTCACCTAAAGGAGTCCCATAGTGAACATTTAAGAGCAA


 


ATGATTCCTTTTTTATTTGTATTTTTGGTTTTGCCTCTAGCACATCAGGT


 


ATTCTTTAAGAAGGCTATGCCTCTGAGGTTGCATGATCATTAACTAATTC


 


ATAATTTCCCTTGCATATATTTGGGTATTTTGGTGTTTCAGCCTTTCCCA


 


CACTTTTTTTATTTGCATGTCTTCACGATCACCATTATATCTTTGTTCCA


 


CCTGTACTATTATTTACTCACTCTTTGTCTTTAAATCAAATCACGTTTCT


 


TACTCAAGTAGATTTAGTTTTAAGACAAACCTTATGGCCGGGCACAGTGG


 


CTCACACCTGTAATCCCAGCACTTTGGGAGGCCAAGGCGGGTGGATCATG


 


AGGTCAGGAGTTTGAGACCAGCCTGGCCAACGTAATGAAACCCCGTCCCT


 


ACTAAAAATACAAAAAATTAGCTGGGCGTGGTGGCGGGCACCTGTAATCC


 


CAGCTACTTGGGAGGCTGAGGCAGGAGAATCACTTGAACCCGGGGGGGCA


 


GAGGTTGCAGTGAGCCGAGATCGTGCCACTGCACTCCAGCCCAGGCAACA


 


ACGCGAGACTCTGTCTCAAAAAAAGAAAAAAAAGGAACTTTATGTCGCTA


 


CCATAAATGTGAAATTACTAGAACTCACAATAAATAGAAGTTAGTAAAGA


 


CACTGAATTCTAACTAGACGCTATTGCTTGTTGAAGGCTTTGATCTTAGG


 


AGGATTAGAAAGCATTCTAGGCCAGGCACGGTGGCTTCCTGTGTGTAATC


 


CCAGCAGTTGGAGAGGCTGAGGCAGGCGGGTTGCTTGAGCTCAGGAATTT


 


GAGACCAGCCTGGGCAACATGGCAAGACCCTGTCTCTACAAAAACATACA


 


AAACTTAGCCAGGCGTGGTGATGGCCACGTATGGTCCCAGCTACTCAGGT


 


GGCTGAGGCAGGAGGATTGATGAACCTGGGAGGCTAAGGCTCTAGTGAGC


 


CATGATCACACCACTGCACTCCAGCCTGGGTGACAGAGCCACACCCTGTC


 


TCAAAGGAAAAAAAAAAAAAAAAAAGAATTCTAGTGGTGTGGTGTGGAAG


 


ACACATTCTCAGCAGACTAAGGTTGTATCTTTATAACCACAAGGATTGAA


 


AAAGAACGGAAGGACAATAACTTTCTCATAAGGTGATTCAATGTTATTTA


 


GTGCTGTTTCTGTGTACCATCAAAAATCCTCTTACTACACACAGAATATT


 


ATAACACCATCTCATTGTCCACATGAGCTCAGAAATTGGTCATCAAAGCA


 


GAAAAGTCTTTAAAACATTGATCTCCGGCCGGGCGTGGTGGCTCACACCT


 


GTAATCCCAGCACTTTGGGAGGCTGAGGCGGGCGGATCACAAGGTCAAGA


 


GATCGAGACCATCCTGGCCAACATGGTGATCCCATCTCTACTAAAAATAC


 


AAAAATTAGCTGGGTGCAGTGGCAGACGCCTGTAATCCCAAGCTACTCGG


 


GAGGCTGAGGCAGGAGAATTGCTTGAACCCAGGAGGCAGAAGTTGCAGTG


 


AGCCGAGATCACGCCACTGCACTCCAGCCTGGGCAACAGAGCCAGACTCC


 


ATCTCGAAAAATAAAATAAAATAAAACATTGATCTCCAAGAAAGTAGATC


 


ATATCTGCTCTCTATCTGACCACATTGTTAAACTTGGTTATGTTTGCAGG


 


TTAAAG


 


Human Genome Map Xp21 (2040 bp sequence)


(SEQ ID No. 63)


30A


CAAAGACAGGCCAGTGCTCTACTCCTTGCTTCCTGGGCTCCCCAAAAGGG


 


AGCTGACTCCTCATCCCTCAACCTGGAGAACCAGTTCAGCTCTTCTTTTC


 


ACCAGAATCCTTTCCCTGCTTCCGACTCATCTTCTTTTTCTCAAAGCTGT


 


TGTAACTGTATTGTTCTCACCTGCTTTGCCCAGACAGATTCCCCAGTCCT


 


CCCCATCAGTGTTTGGCATTTATTCTGGGTGTTCTACTAGTAATGCCCAG


 


CCCCGGTCCTGGGCTTCCTGCTGTTTCTATTGCATCTCCCTAACTCTTAC


 


ATCCACCCCAACTCAGTGTTTTTGGCCTTCCTCAGCAACCAGGAATCTAA


 


ACCACCCTCCACCCCATAGCACCCTATGGATGACGGAGCCTTAGTTCTTG


 


ATGGTGATGCAGACACCTTGAGGTGTGGCCATGACATTCACTCAGCCCTT


 


GGCCTGGTAGCAGCAATTTTCCCTGATAAGGTCCCCAAACTGACCCTCAG


 


TTGTCCCCTGCAGTCCCATTAGGGCCTGTGGAATTTACGACTTCCATACA


 


CAGCACCAGGAAGTTGAGGATGGCTCCACGTGCTAGCTCAGTCTCTTTGC


 


CCTCTCTCTGCCTGTGGCAGATTGTATTTTCCAAAGATGACTGCACCAAA


 


ATATTCCACCCCATGTTATCTTCTTATGTGAAGTTCACACTAATTCTTCA


 


AGAAATGGGGCCTCTGTTTACACCTGCTGAATCTTGGCAGGCCTATAATT


 


ATAGTGGTTATGATTCTAGTGATGCTATATGACTTCTGAGACCATAAAAA


 


GACAATACAGCTTCCACCTGGTCCTATTGGAACAGTCATTCTTGGAACCA


 


AGCCACCATGTTGTGAGAAAACCCAGCCCACATGGGAAGGTCACATGTAG


 


GGATGACAGTCCCCACTGAGCCCCAGCCAATAGCCGGCATCAACTGCAAG


 


ACATGTGAGTAAGCGAACCCTCAGATGATTCCAGCCCCCAGCCTTTGAGC


 


TGCCCCAACTGATGCTTTGTGGAACAGAGAAAAGCTGTCCCCATTGAGCT


 


CTGCTCAGATTTCACATTTATGGTAAAAATCTATATGGTCCTTACTTTAA


 


GTTACTAAATTTGGGGATGCTTTCTTTACATAGCAGTAGGTAATTAGAAC


 


ACTGCCTGATCAAACTGCACTGCAACTTTTACTCGGCTGCTAACTATATG


 


GCTATAGCCGAGCATCATGGGGCCACCGTGTCTGGCAGTCCCCACATCCG


 


AGTTCCAAATGCGGAGCACAAAAGTCCCACTGTCACTGATCTTCCCTTCC


 


ACTCTCAGAATCTCAGTCTAGTATGGGGAAGCAAGGGTCGAACCATGTGC


 


TTCCCCCGTCAGGGCAGATGGTTCTCTTCCTGCCTGGAAGGAATTCCCTC


 


TACATAAAAGCCTCTTTCCACCAGGTATGGTGGCTCAAGCCTGTAATCCC


 


AGCACTTTGGGAGGTGAAGTGGGCAGATCACCTGAGGTCAGGAGTTTGAG


 


ACCAGCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATATAAAAA


 


TTAGCTGGGCATGGTGGTGGGCGCCTGTAATTCCAGCTACTCGGGAAGCT


 


GAGGCAGGAGAATCACTTGAACTCGGGAGGCGGAGGTTGCCGTGAGCCGA


 


GATCATGCCACTGCACTCCAGCCTGGGCAACAGAGTGGGACTCCATCTCA


 


AAAAAGTAATAATAACAAAAAATTTTTAAAAAGTGTTCTTCTTCCCAAGA


 


AAGCAGACATCAGACATCTTTCCCCCTTCATTGGGGCCTTAATTGCAGAT


 


GGGACTCTGGAAGAGATACTGACATAAGCATAAAAGTAGGTCCAAGAATA


 


TTTAACCTCTACATAAGAATTCAAATAAGCTATTGACCTTATGAGAGAGT


 


CACAATGATGGACACCTTCAAAGGAAGGAGAAGCACCATGGAGGGCAGAG


 


GAGAAAGACCATACCTGCTTGACTTGGTGTGAGAGGCATTCTAGATGTTA


 


TTGACATCATATAATAGACAGATGACAAGCATAGAAG


 


Human Genome Map 12q21 (2100 bp sequence)


(SEQ ID No. 64)


31A


TGTACATGCATTCATTTTGCTATCCTGCATTTGTTCTTTCTTCCTCAGAC


 


CTTTTCAGTCCCTAAGAAAATGGTATCATTCTGGGTAGGACCTAAGATCA


 


GTGATGAAATAACAGAATGCAGGATGGCAAGACTCTATATGGAGAGGGAA


 


ATTTTACAGAATCTAAACCTGGGGATACTAAATTAGATCAATTGAGTATA


 


GGCAATATCAGAGGGTAATAAAATAGTTTAAGAATACATAGATGTTTTTT


 


GTTTGTTGGTTAGTTTTTGCTTTTCTTGTAATTCAGGTTAAAGATGTGAC


 


ATTTCCTAACAGCACCAAGGAAGGAGCACCAGAGAACATGAAAAGGCACT


 


CAAGCTAAGTGGTCTGTTGAACTTTGCATATCTTCCTCTTTGTCAATGAA


 


AGAAGGCAAAACCAAACCTAAATGACAAAACAAAGAACTACTTACAAGGA


 


GTTTTAAAATATCTCAATCTCTGCGTTACTTATGTAACCCACAGAGTATA


 


TAGATGACCACTTAGAGGTATTCCTACTATTAACAAAGGTATTAGTATCT


 


GTGTTTTACCCATGAAAAATTAGAAACTTAGAAAAATATCTTGTTCAGTT


 


TCACACTGGTACAATATGAGGGTATGAAAGTTGTAACTGACTCTAAAGCT


 


TGAGCTATTTTCTTATAGATATAATTTAATAATGTCTATCAACTTTCTTG


 


AAATATTCTCATTGTTACCTAAGAATTTAAAATATTGATATGCAATTGAT


 


CTAAGAGAGGTTAAACATGAATTGGAAATTCCTTCTCCGATATCAGGTTT


 


GATTTTTCACAAATATCAATGTTTATGAAAGTATTCCTAAAATTTCAGGT


 


AAACCACCCAATAATATGACTGTGAAAAATTATGCTTCTTCCTCTATGAG


 


CTACTACATTCTTAAATTATCTGAGCATTCTATTAAAACTTAAAAAAATG


 


CTTAACTTGAGTCTGCATGAATCTGAATTCCCTGCATATTTAATTTTAAG


 


AAAATAGTTTATTTTTTTGTTAGACCAATACTTTACAAACTTCCCCAACC


 


AATAAGAAAGAACAAAGAGGAGAACATGAATATCCCTGGGTATTTGTGAG


 


TAAATCCCCAAGAGACTAACCATAAATGTGAAATTTCTTTATAATTGTAT


 


GTCTTCTTCTAAAATATTCATGTGGATTGTGCATTCTATTCTATCTTCTT


 


ATTTTAATAAAATCTGTTTTAAATTATTTACTTCCTGGAACAAATCTCCC


 


TGTTGTGTTGGTTTATGAACATGGTTCTATTGCCTTCAGTCTATTGTCGG


 


AAATAAAAACAGTCCTGCAGTTGTTGATTGAGTGTACTATGCCTTTAAGA


 


AGTCATGGCACTCATGCAACAGCCATGTAGTTGTTGATTGAGAGTACTGT


 


GTCTTAAAAAAAGAACTTTTGCTAAATAAACTGACTCTGTGAGCAGCCCT


 


TCATCATTTAAGTGAGAAATGTATTGAATTAAGTTACCTTGATATTGCCT


 


TTTGTTATATTTTTATTTCTTTGATACAAAAGAGTAACAATTTAATTCGA


 


AATTTGAAATCCCTGAATTGCCTATCCTCTCCAGTAAGTCACTACACACC


 


TGTATAGGGGAGCAGCCTTTCAGAATATTTTTCCTGAACATGAGAATATA


 


AAGCAGGAGGTGGTCATATTTGTTTGAGTAGCACCTCCTGATACCATTAA


 


TCTGAGCAGAAGAGTATGGGTCCATACTAGAACAGGATATGACTAGGAAA


 


ATGAAGAAGAATGAAAGCAAAGTATTCAACAGAAACATCTATGCTTTTTG


 


CCATTAGCTGAATGTGACATAAGAGTATAGAATGATTTGACACGATTCCA


 


AATCTAAATGTAACCAAGGAACTTTAAATATTATTAATGAGCATGGCAAA


 


GTTTAGGGTCAGGGGGAACAAATTTAAAAACTATGAGCATTCTCATGACA


 


TGAGTTAAAATGCAAAGACGTAAGTTAAACATAACTAATGACATTAATAA


 


AGTGATTGAAGCTCTATGTCACTTAAAGATAAGAAGGTATGATAGTTTAG


 


ACATTGTTCTAAAGGCCAATCTAAGTGAAAAAAGTTTTCAGG


 


Human Genome Map 17q21 (2100 bp sequence)


(SEQ ID No. 65)


32A


AGTTAGAATTCTGTGAGGTTTGTATAAAAGGAATAGAGTGGGGGCCCAAA


 


AACCAGTAAGATGAGAAAGTACTGTTTGCTCAGTTCTAGGATCCATGAAA


 


TAAATAATAAATAAATAAAAAAGAGAAAGTAGTGTTTCCTGCCACTTTAG


 


AGGAAGGACTCACATATCCTACCTTCCATCAGCCTTGAAGGAGATGAGTG


 


CCCTCTCTCCAACACCTGGTGGCCTTCCCTACCCCTTCCCCAAAGCCTCC


 


AAGAAGGCCCCTGGCCTAGCCTGATGCCCACTATCAGCAGGAACAGGCAC


 


GACAAACTTTCCCCTTCCTATCCCTCCCCACCTCTGGAAAGGGCTGGGGA


 


CAGCAGATGTGTCCTTGTTAGTTCCATCCATTTCAGCTTTGGCTGGGGAG


 


CTAATTTCACTGGAGCCAGGATAAGCATTAGGGTAAGTAACTATTTTTCC


 


TGTCTTGGGCAGTTTCCTCACTGACAAATGAGGGCAGAGTTCTAAGCTCT


 


CTTCTAATTCTAAAATTCTAATGTAAAAATTGCCAGACTAGTGGTGGCGC


 


AAGCCTGTAATCCCAGATACTCAGGAGGCTTAGGCAGGAGAATCGCTTGA


 


ACCCAGGAGGCGGAGGTTGCGGTGAGCTGAGATCGCGCCATTGTACTCCA


 


GCCTGGCAACAAGAGGGAACTCCATCTCAAAAAAAAAAAAAATCACCAGA


 


CTAATATTTACCTTGAGTGTTATGCGCATCCATGTGAAGAGACCACCAAA


 


CAGGCTTTGTGTGAGCAATAGTTTTTTAATCACCTGGAGTCAGCAAAAGG


 


AGATGGGGTGGGGCAGTTTTATAGGATTTGGGTAGGTAGTGGAAAAATTA


 


CAGTTAACGTGCGTTTTCTCTTGTGGGCAGGGGTGGGGGTAACAAGGTGC


 


TTGGTGAGGAGCTCCTGAGACTCATTGTCCAGGAGAAGGAATGTCACAAG


 


ATCAATTGATCAGTTAGGGTGGAGCAGGAACAAATCACAATGGTGGAATG


 


TCATCAGTTAAGGCAGGAACTGGCTATTTCACGTTTATGGTTCTTCAGTT


 


GCTTCAGGCCATCTGGATGTATATGTGCAGGTCACAGGGTTATGATGGCT


 


TAGCTTGGGCTCAGGGGCCTGACATTGAGGATTCTTTTTTATCTTCCTCT


 


GATGCTCTTCTATAAGAATGACTCTGTTTTGGAAGAAAACGCAATTAAGA


 


TTTTCCATCACAACAACCACTATCTCCAAATCTGTATTCATTCCTTTTAA


 


TTCATTATAAGTCTCATCTACCTAATGAGATAACTTTTTTGAAGACAGGA


 


ATTGTATGCTGTTTAACAGTGCTTTGTTTCTTCCATAGTTCAGTCATCCT


 


TGATATTTTGCGGGGGACTGGTTCTAGGATACTGCCCCCACACACCAGAA


 


TCTGTGAACGCTCAATCCCTTACATATAATGGTGCAGTATTTGAATATAA


 


CCAACACACATCCCCCCGCCACCACCCAATTAACTTTTTTACTTTTTTTC


 


CCCCCCGAGACAGAGTCTTGCCCTGTCGCCCAGGCTGGAGTGCAGTGGCA


 


CGATCTCGGCTCACTGCAAGCTCTGCCTCCTAGGTTCATGCCATTCTCCT


 


GCCTCAGCCTCCCGAGTAGCTGGGATTACAGGTGCCCGCCACCACACCGG


 


GCTAGTTTTTTTTTTTTTTTTTTTCTTTGTATTTTTAGTAGAGATGGGGT


 


TTCACCATGTTAGCGGGTGGACCTTGTGATCCGCCCACCTTGGCCTCCCA


 


AAGTGCTGGGATTACAGGTGTGAGCCACCATGCCCAGCCAATTTTTGTAT


 


TTTTAGTAGAGACGGGGTTTCACCATGTTGGCCAGGCTGGTCTCGAACAC


 


CTGACATCAAGTGATCCGCCCACCTTGGCCTCCCAAAGTGCTAGGATTAC


 


AGGCATGAGCCACCGCACCCAGCCTCAGACTAAACTATAATAAAAGAGAA


 


AGCAGAGAGAGTAAGAGCACCTCATATGGAATCACCTACATTTCAGAAGC


 


TGGAAAGAAAGAGAGTGGTCTACTTGATGATATGAAGCATGATCAATCAG


 


TATCAATACTAGCTTTAGGGTGAAGGCATAGCCAAATTGGAAACTGTGGA


 


Human Genome Map 1q32.2 (2100 bp sequence)


(SEQ ID No. 66)


33A


AAAAAAAACCTTGTCCAGGCACAGTGGCTCACATCTGTAATCCCAACACT


 


TTGGGAGGCCAAGGTGGGCTGATCACTTGAGGCCAGGATTTTGAAACCAG


 


CCTGGCCGACATTGCAAAACCCCACAAAAACTAGCCGGGTGTGGTGGCAC


 


ACACCTGTAATTCCAGCTACTTGGGAGGCCGAGGCACAAGAATCACCTGA


 


AGCTGGGAGGCAAAGGTTGCAGTGAACCAAGATCATCCCACTGCACTCCA


 


GCTTGTGACACAGTGAGACTGTCTCAAAAAATAATAACGAAAATAAAATA


 


ATCTAAAATTTAAAAAAACCCTAATTCATAGTTATGGAATTATTGAGCAT


 


ATTAAATAAGATAATGCATGCAAAGTACTTAACAGCATCGGACATATTTT


 


AAGCACTCACTGATGCTTGCTATATAGTTAAATTATATAGCTATATGTAT


 


GTGTATATACATGCAAAGATCAGGAGATATGCTGACATAGAATGACTATG


 


GCAGGGTCCTGAAAGAGACCACAAAAGAGAGAAGTTTTCACACTGGTTCT


 


TTCCTTTTGGGGGATGCTGACAGTTCCCCTAGAAGGCAGCAGACTTTGCC


 


TCTGGGAGCAAGCCACTGGCCTGGCCCAGCACTCCTGAGATGAGCAGAAA


 


TGGGCAGAGGAGAGCTCAAGACAGAGCACAGGCCAGACTAATGTCTTCCT


 


GAGAGGAGAGCAGTGGGAGGAAAAAGGGGGCAGCAAAGAGACAAGAGATT


 


GCCTCCTTCACCTCCACCAATGTTACCTAAGCTAAAACCCCTCTGTCTAC


 


CAAATCAGCCCTGGTCACAAACTAAAACCCAAACCCAACAGGAGGCTTAC


 


TTATCCACGCCAATCTGAATTTCTCCATGACATGGACCAGGTGGGACTGT


 


GGGTTTGGTGCCATGTACATGACCTGTGACTTAGTGGATGGAGTTCCTTA


 


GGCCACAGCAGCCTCTGGCTCAATGAAGCTTGATCTACTGAGTACCTGGA


 


CCACATGGGGCTCTAGCAGCAGTCCTATCTTGAGCCCAGAACAGTAACTT


 


TCAATAGAATATACACTGGTATGTTGAATCAGAAGTTCAAACGCCCTTCA


 


CCTTTATGGTGACTTTTCTCTCAAGGACCTCCACTGCTTTCTTCTACTAT


 


GCCTTCGTATCATTGACCATTCCATCAGTGAGGGCCACCACAGTCCCTCA


 


GAATTCTTTAAGACTAACTAGGGGGAGATTAGAGTACCAATCCTTCTAAA


 


CCTTTCAAAAGGCTTCTTTTGAACCCTTTTCAAAAGATTTCTTCACTTAG


 


CACCCTGGAACCAAATGGAAGTGAATATTTTTGAGAAGACGTGACATCTT


 


TCTCCTGGGCCTTGCCCAGCCAAAATGTTCTGTTATCTGTTGCAATTAAA


 


AGAGAGCAAAGAGTAAGAAGTCTCTTTCCTTAAAGTTTCTTTGGCCACTT


 


GAGCGGAGCTTCCCAGAGCAGTAAACTCCTTTAGGATAGGGACTGTTGGA


 


ATTAAATGAGCTGGGGAACCACAACCTAGAAACTGGACTTCAGCTTTGTA


 


AACTCCGAAACTCATTATCACTGTGATGGTTAATTTGATGTGTCAACTTG


 


AGTAGGCCATAGGGTGCCCAGATTAAATGTTGTTCTGGGTGTGTCCATGA


 


GGATGTTTCCAGATGAGAATAGCATTTGAATTGGTAGACTCGGCAAAGTA


 


GATTGCCCTCCTCAGTGTGGCTGGGCATTGAAAAGGCCGAAGAAAGAATT


 


TGCCCCTCTTTTCCTGCCTCACTATTGAGCTGGGATATCTCATTTCACCT


 


TCTCCTGCCCTCAAACTGGGATTTACATCATCAGCACCCCTGGCTCTCAG


 


GCCTTTGGACTTGGACCAAACTGCATCACTGACTTTCCTCCATCTCCAGC


 


TTGCAGACACAGATTATTGGACTTCTCAACCTCCATAATCATGTGAGCCA


 


ACTACTCATAATAAATAAATAAATAGGCTGGGTGTGGTGGCTCATGCCTG


 


TAATCCCAGCACTTTGGGAGGCCCAGGTGGGCAGATCACGAGGTCAGGAG


 


TTTGAGACCAGCCTGGCCAATATGGTGAACCCCCATCTCTACTAAAAA


 


Human Genome Map 5q15 (2040 bp sequence)


(SEQ ID No. 67)


34A


TACAGGATGAAGGTAACAATAAGAGAAAGTGATCATAATAGTCAATATTT


 


AATACATATTTAATATATATATTTTTAGATTTAACAACTGGTTAAATCTA


 


TTAACCATATATCATCTAACCATTTCTATACCTTCCTATCACTCTTCTTT


 


TCCTATTCTCTCTTAATTCCAATTTTCCTACAACACACACACTCATATAC


 


ACATACGCACACATGCACCCACTATCCATAAGACCATCACGTCTGGGGAT


 


TTTGCACATACAGAGCCTAATAAAATTCAGCAACAAAGATCATTCAAATT


 


CATAACTCAAAAATTATCAGGTACAGAAAATACATGAACTGAGGTGAAGA


 


AAAGCCAAAATACTGGGAGAAGTAGAATATCTTTCACAAAAGACCTTCTA


 


GGAAGATCATATGGTACTGTTCTGCAAATCTTTCCTTTTACAACATTGAA


 


TGTTTTAATGTGAGCTTTGCAGATTCAGTTTCAAATCTTATCACTAATCC


 


TGCCCTTAAGCAAAGCTGTAAAGAAGGTGAAATTAATTTTATACATTTCC


 


TATTCTGCATTCTGTCATCCTCATCTTCCTTTGAGGGTCTAACAACTTCC


 


TACCACTTTCTGCTTGTGCCCATTACAACCCAGATTTTCATCTTTTGTAC


 


CTGGAACAGGCCTGGCCTTCCACAATGCTCTATGTGCTATGAAAGTCAGT


 


TTCTGCTATTATCATTGTGTTCTATTATTTCATGTATTTTCTAATAGCCT


 


TAGATTACTTTGAATAGGCCTGGAATCTCTAACACAATTAAATACTATAG


 


CAGGCATATAGTATTACCAAGGAAAGTAAAGCAAGATATAGAACAAATTG


 


AATGATGAAAACTGAGACAAACTGGAGACAGGGACCATGTCCAAAATGGA


 


CATCCATTATTCAACTGTAGCCTCATGTTATCATGTGGGAATGAAGGCCT


 


AGTGTTGTAAGATTTTAGATTTTTCAAGAGGAGCCAGAAATTTGTACCTT


 


CATACAAAAATTTCAATATTTGTAAAACACCATAAAAGTGAAAAAAATAC


 


CTACAAATCAGAATTTAGACTATGTTGACATTAACTTGCTACCTCTGTGA


 


TAAGCGATTTTAGAATAAGATTTTATTCTTGCTTAATTCTTCTCTTCAGA


 


GATACCTAGTGTAGTAGGAGAATCTAACACTTAAAAACAGGTCAGGTATG


 


GTGTCTCACACCTATAATCCCAGCACTTTTGGAGGACAAGGTGGGTGGAT


 


TGCTTGAGCCTAGGAGTTTGAGAGCAGCCTGGGCAACAGAATGAGACCCT


 


GTCTCTACAAAAAATACAGAAATTAGTCAGCTGTAGTGGCCTACGCCTGT


 


ACTCCCAGCCATTTAGGATGCTGAGGTGGGAGAACACTTGAGCCCAGGAG


 


GTCAAGTCTGCAGTGAGCCATGATCATGCTACTGCACTCCAGGCTGGGCA


 


AGAGAGCAAGATCCTGTCTCATATAATAATAATAATAGTAATAATAATAA


 


CAATTTTGTGATGGGTGATAAATATCATAGGGGCAAAATGTCATGGGAGC


 


ACAGAGATGGGAGAGGGGACTTTCATAAGCCTAGAATGTTCTCAAGGAGT


 


ATGTCTCAGAGAATATGAATCTCAAATGAAAGTAGGCCTTTACCAGAGAG


 


AGAGAAAATAAAGAGTATTCCAGAGAGTTGTGTGTGGGAAGATGCAGACA


 


TAAGAAACAGCAGCATTTACTTGGGGAAAAAATAGTTTAGGTTCTGTTCC


 


CAGATAAGTGGAATTATATCAGATACAGTTTTTAAGGAGAGTCTATTTGG


 


GGCAGGAGGGCCTCTTGAGTTCTTATTAATAGTTTTAAAATGTGAACACA


 


CCTTACTGCACATTAAGCACATGTACCCCAGAACTTAAAGTATAATAAAA


 


AAAAATTTTAAAAAAAGAAAAAAAATGTGAACACACCTCTATTTCTCTCT


 


CCAGGTAATTTTAACATGACCTTGCTACTCCCTTGGATGAAAGGATCATC


 


ACGAAGTTTTACAACAAACTTTATGGTTATGGAAGTTCT


 


Human Genome Map 8p11.2 (2100 bp sequence)


(SEQ ID No. 68)


35A


TCTAAGGCTTCTGGACCTGAACTGAGCCATGCTACCAGTATTTCAGGATG


 


TTCAGCTTGCAGATAGCCTGTCGCGGAACTTCTCAGCCTCTAGAATCACA


 


TGAGTCAATTCCCCTAATAAATCTCCTTTTATCTATCTGAACATCTCTCT


 


TCATCTCTCCATCCATCCACTCATGTGTCCATCCATCCATCCATCTATTG


 


CTATCTATCTATCCATCCATGCATCCATCCATTCAACCATCCATCCACCC


 


ATCCATCCATCCCTGTGCCATCTATATCTATCTATCTATATATCTATCTA


 


TCCATGCATCCATCCATCCATCTATCCATCTATCCATCCATCACTATCTA


 


TCCATGCATCCACCCATCCACCCATCCATCCATCCATCCATCCATCCATC


 


ACTATCTATCCATCCATGCATGCATGCATCCATCCATCCATCCATCCATC


 


CATCCATCCATCCATTTATCGCTATCTATCTATCCATCCATGTATCCATC


 


CATCCATCTGTTCATCTATCACTGTCTATATATCTATGTATCTATCTATC


 


CATCCATCCATGCATCCATCCATGCATCCATGCATCCATCTATCACTATC


 


CATCCATCCATCCATCCATCCATTCATCCATCTATCTGTCTTCTACCTAC


 


CTACCTATCTAACTCTCTGGAGAACTCTGACTAATAAACTAGCTTTATAA


 


ACATGTTATTCTCTCTCTGCAATGTCTATTGCTTTATCTTCAGGAACATT


 


CCACACATCCTGTAAGACTTCAGTTAAATTATCTCTCTGTTTCTTCTCCA


 


ATCATCCTCTGCCTTCCCTAGTCTCCTAACGTACTTTGTACATCTGTCAC


 


AAACCCCTCATCATATTTACTGTAATTTTTTTCCTACAGATTTGGATAGG


 


AATTGAGCCATTTTTTTAATTTCACTTTTATGGTTGTTACAAATAAAAGA


 


GCAAGCAGGCCCCTCACTGTAATTCACCTGTATTTGCATTTAACTTATTA


 


ACCAAGGCATACTATTTCAATAATCTAATATAGTATTTCCTATTTAATAA


 


CCAAACATACAGAACAGTTCCAAGCACATGTAACCATGTGATACATTTTC


 


CTCTTTGAATAATAATATATTTCTTATAATTAATATGTGATAAAATTGCA


 


ATATTTTTAATCTCCTACATCCTTCTCTTTTAATCAGGTTTCCTTATCAA


 


CTGGTTCCTATCTCACGGGGTTGTTGCAGAGATGAGGAAAAAAAGTATTC


 


TATTGGTTCATGCATCTCAAAATAGGCAGATTCTTTTCTCTGCTTCTTCC


 


TTCATTGGCTCAGGTGTGGAGTGCTTCTCCCAATTATATGTGCCAGCCTT


 


GGTATGTTCTCATTGCTGTACCACACTGCCTGAGACATCCAAGACCACAT


 


CTTCCTTTGGGGGCACATTGGACCTTTGTCATTGGCACTGGCAGGGAAGC


 


TTTTATTTCACCAGGTCTAAGGCAATTCTTCCAAAAAAATCCCAAATAGT


 


GAAAGAATTGATTTATTCTTCTAATATTTAAGCAAATGTAAAAAAAAAGT


 


TACATTAGTTATGTTTTTTTCAGATTTTGGATCAGTGAGACTTCATTAAA


 


ACACTTTGAGGTTATAAAGCAAGTAATTTTTGTTTCCAGAAAAGTTAGTT


 


TCCTTTGGCTGAAGGGACATCTCTATGCAGGCCAGATCAAGACAAAAATA


 


ACTTTTAAGAAGGGAAATGAGGGAATGGAGTTTGGAAAACATAAATCCCA


 


CAGCAAAGTACGTCACCAACAATAAGAGTCATCTCTTTCACAGAGGCCTT


 


TCCTAGAAAAGCCCTGACAGACTAGGAGTCCAATCTTCGGCTCCCATAGC


 


ACCCATGCCTGCTTCCACTCTGGAGCTTACTACTTTGCGTTGAAATTAAT


 


TTTTACATGTCTATGGCTTCTATTACAAATAGCTTATTGAAAAGAGAACC


 


ATGTACATTACAATACTTTTTTAGAGTTGCTGAACTGAACAAATCAGTAC


 


CTACGGGGTTAGTATGCTGGCTTCTATTCCAGCAGGGTTTTGAGCCATGA


 


GATTTTGAATGCTCCCGACATTGTTAGTTCAGGATGATTAAAAATAT


 


Human Genome Map 3p12 (2040 bp sequence)


(SEQ ID No. 69)


36A


TGAGAAAATGCAAGAAAGGAAGCCAGAGACGTTGTGGACTGCAGGCTCCT


 


TCCCCATCATGTCACTCAAACACAATGTTTCATTTGTAAAACATATTTTA


 


AAAGATTATGAATGCTATTTAAAAGAACACTAAAGGCCGGGCACAGTGAC


 


TCACTCTTGTAATTCCAGCACTTTGGGAGGCTGAGGTGGGCAGATTACTT


 


GAGTTTAGGAGTTTGAGACCAGCCTGGCCAACATGGCAAGACCCTGTGTC


 


TACTAAAAATACAAAAAACAAACAAACAAACAAACCCAACATGGTGATGT


 


GTGCCTGTGGTCCCCACTACTTGAGAGGCTGAAGTGGGAAGATCACTTGA


 


GCCTAGTAGGTGGAGGTTGCAGTGAGCCAAGATCACACCACTGCACTCCA


 


GCCTGGGTGACAGAGCAAGAATACATATATATATATATATATATATATAT


 


ATATATATATATATATATATGTATATATATATATATATATATATATATGT


 


ATATATATATATATACAGCAATCAACCAAACAACAGCAGCAAAACATTAA


 


AGTGACATGCTGACTCCTTGGAAAGGTGGTAAGCTCTTTAGGCTTCCTAA


 


TCAGAGAAGGCAGATAAAGAGTAATTTAACATCTTTCTAATCTACCCCAA


 


TGGAATTTGCAGTGATTTTCTTTCCATTTTTTCTCATTGTTTTTCAACCT


 


GATCACTAATAGGTAGCTGAAATGGAGTCACTTAATGGTTTTTGCTTTTT


 


AAGAATTCCAAACTCACAGTTTGAAAATTATAGTTCTTGCATTTGAAGTT


 


TTTCTTCATCGTGCTTGGCCTGCCTGGTGGCTTTTTGTTTTGTTTTGTTT


 


TGGTTTGGTTTGGTTTGTGGTCTCTTTCATCTACCCAAAGCCAGTTGAAA


 


TAAATCAAAAGTTGTCTCACTCAGGAATTGTCTAAAGTAAATAAATGAAA


 


AAAAAAAAAAAAACAAGACTAATAATTAGGCAACTCATTGAGTAGGCTGT


 


TGAACCAGCTAAAGTGGGAAAGAAATTATTCAAGTTCTAAACCTTTCTAC


 


TTGCAAATTAGCCAAAATCAATTGCATTTTAAGCACTGCATCACCTTGAT


 


TGATTTTTAAAATGGATAGCACTTTGCTGTTCACATTTATGGTGAGCCGT


 


GAAGGACTTGGCAATGGGCATCTTTTCTACCGTGTTCTGCATTAAACTCT


 


TTAAATAGCTTCTGCTTCTTAATGTTGAATGAACTTTACTGCAGACTGAG


 


TCTGAGGGTTTTTTTTTCAAGGTTGAAATACATTCTTCAGACTTTACTTT


 


TTGCATGTAGCATTCTTCTTACTTAAAATACCTAAGAGTTTCTAACTAAT


 


TTCTTTCAGCCACAGGAAATATTTCTGTAATTTTAGGGTTAAAATGGAGA


 


ACTATAGGATGAAAATATAATACAAGAAAATGAATTAAACCCTAAAATTT


 


ATTATTATATGTGGGTAAAAGTAGGGGGGAAAATCACTGGTTTTGAAATT


 


AAAAGATGAAAATTGTGAACACTTGCATGGAGACCCTATTTGTAAACTTG


 


GACAAGCTTCAGTGCCCTCTCTCTGCATCTTCTGTCATTATTATTTTTCC


 


TCAAGGCATCGTTTTGAGGATTAAATTAGAAAATGTGAACTAGCTTGAGA


 


GTACAGTCAGCACTTGAACAGCATGGGTTGGAACTGCAAGAGTCCACTTA


 


TACACAAACTGTTTTCAAACAAGCTCTGATCTAAAATACAATATTTGTAG


 


GATCTAAAACACGTGTATACAGAGGGCCAACTTTTCACATATGAAGGTTC


 


TGCAGGGCCAGCTGCAGGACTTGAATGTGCCTGGATTTGGGTATAAACAG


 


GTAGTCCTGGAACCGATACACCAAGTATACTGAGGGACAATTGTAATAGG


 


CACAAAAATGTCGATTGATAGATTTTGTTCTTTTTCCTGAAATGCAAACC


 


AGGACACTTACAAAACTAAATGAATAATTACTTATACATTTAGTGTCTCT


 


GTGCTTCTCTCTTTTACCTTTTCCTACTTCTTCCGTAT


 


Human Genome Map 14q13 (2100 bp sequence)


(SEQ ID No. 70)


37A


AAGTACAATTGGCCAGGCGTGGTGGCTCATGCCTTTAATCCCAGTACTTT


 


GGGAGGCGAAGGTGGGCGGATCACTTGAGGTCAGGAGTTCAAGACCAGCC


 


TGGTCAACATGGTGAAACCCCGTCTCTACTAAACATACAAAAATTGGCTA


 


GGCGTGGTGGTGGCACCTGTAATCCAAACTACTCGGGAGGCTGAGGCAGG


 


AGAATGGCTTAAACTCAGGAGGCGGAAGTTGCAGTGAGCTGAGATCGCGC


 


CGCTGCATTCTAGCCTGGGCAACAGAGCAAGACTCTGTCTCAACAAAAAA


 


AAAAAAAAAAAAAAAAGTACAATCAGTGTTCTGTTGTGTTTTGTTGTTGG


 


TTTTTTTTTTTTTTTTTTCTTTTTTTAGACAGGATCTTGCTCTGTTGCCC


 


AGGCTACTATGCAGTGGCACAAGAACAGCTTACTGCAGCCTTGACCTCCT


 


GGGCTCAAGTGATCCTCCCACCTCAGCATCCATAATAGCTGGGACTACAA


 


GTGCACACCACCACACCCAGCCAATTTTTTAATTTTTTTGTAGAGACAGG


 


GTCTTACTATGTTGCCCAGGCTGGTCTCGAACTCCTAGGCTCAAGTGATC


 


CTCCCACCTCGGCTTCCCAAAGTACTGAGATTACATGCATGAGCCACCAT


 


GCCCAGCTCTATTGTGTTTCTTGTTTTTTAGCTTGACAGGAGGGTGTCAG


 


GGATTTCCTGGCTTACAGAAATGATATGAATTTGCAGAAGAAACTAAAAC


 


TGTTAACAAACATTTGAAAAAAGTTAGCCCCATTATTTATTTTTTAAATG


 


CAAATTAAAACAACATACCTCAGATTTAATGTAACTTCTATCAAAATCTC


 


TGCTGGCTTCTTTGTAGAAATTGACAAACTGATTCTAAAATTCACATGGA


 


AATTCAAGGGACCAAGAATAGCCAAAACAACTTAGAAAAGGAACAAAATT


 


GGAGGGCCCACACTTTCTGACTTCAAAACTTGCTAGAAAGCTACACTAAT


 


TAAGACTGTGTGGTACTGGCATAAAGACAGACAAACAGATCAATGGAATA


 


AAATTGAGAGTCCAGAAATAAACCTTCACATTTATGGTGAATTCATTTTT


 


AAGAAGGGTACCAAGATAATTCAAGTAGGAGAAAAATAGTCTTTTCAACA


 


AATAGTGCCAGGACAACTAGATATCCATATACCAAAAAGTGAAGTTGGAC


 


TCATACCAAGTACAAAAATCAACTCAAAGAGAAAAAAAACCTAAATGTAA


 


AACTATAAAACTCCTAGAAAAAAAGATGTAAATCATTGTTACTTTGGATT


 


AAACAATGGTTTCTTTTCTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGC


 


TCTGTCACCCAGGCCGGAGTGCAGTGACACAATCTTGGTTCACTTCAACC


 


TTTGCCTCCCAGGTTCAAGTGATTCTCCTGCCTTAGCCTCCCAAATAGCT


 


GGGATTACAGGTGCCTGCCACCACGCCAGGTTAATTTTTGTATTTTCAGT


 


AGAGATGGGGTTTCACCATGTTGGCAAGGCTGGTCTAGAACTCCTGACCT


 


CAGGTGATCTGCCCACCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTG


 


AGCCACTGCGCCCACCCTAGACAATGGTTTCTTAAGGTACAAAACCAAAA


 


AGACAAGTTATGAAAGAAAAAAAATAGATTGGACATCATCACAATTAAAA


 


ACTTTTGTGCTTCAAAAGTCATCTTCAAGAAAGTGAAGCCAAAAACAGAA


 


TGGGGGGAAAATTTTGCAAATATATATCTGAGAAGGACCTAATATCCAAA


 


ATGCATAAAGAACTCTTACAATTCAATAATAAAAGAAAATCAATCCAATT


 


TTAAAATAGGCAAAGGATCTGAATGGACATTTCTCCATAGACTATACACA


 


AATGGCTAATAAGCATATTAAAAGATGCTCAACATCATTAGCCATCAGAG


 


AAACACGAGTCAAAAATCACTTACGATACCACTTCACACCTATTAGTACG


 


ACTATAATAAAAAAGACAGTTAACAACAAGTGCTAGCAAGGATATGGAGA


 


AATTAGATCCTTTATATACTGCTGGTGAGAATGTAGAATGGTACAGCCCT


 


Human Genome Map 4p15.31 (2100 bp sequence)


(SEQ ID No. 71)


38A


TAGAAATATTGCAATGGAAACTTCAGAAGTAAAAATGATTATAACGGGCT


 


ATTATAAACAATTATGTGCAATATTTAATCAGGAAGAAATAGAAAGCTTG


 


AATGGACCAATAAAAATTAAGAGATTGAAATATGAATTCACTTTGCAACA


 


AAGAAAAGCCCAGGACGAGATGGCTTCATGAATGAATTCTACTAAACATT


 


CAAAGAAGTATTACCAATATTTAAATTCTCCCAACAAATAGAGATAGAAG


 


AAATACCTGCAAACACATTTTACAAGGCAAGCATCACCTTGATCCCTAAG


 


CCAATGACATCACAAAAAAGAAAACTATAGGCCAATATCTCTGATGAACA


 


TTGATGGAATTCTCAATAAAATATTAGCAAACAAAATTCAACATCACATC


 


AAAAAGATTATACATCATGACCAATAGGATTTATCCCTAGCATGCAAGGC


 


TGGTTTAATACACGAATGAAACAATGTGACACATCACATTAACAGGATGA


 


AAGATAAAAAACACAGAATTTTCTCAATCAACACAGAAAAAGCATTTGAC


 


AAAGTTCAGCATCCTTTCCTGATAAAAACTCTTAACAGTTTATGTATAGA


 


AAGAAAATTTCTCAACATAATATAATAAAGGTGATTTATGAAAAATCCAC


 


AGCTAACATAATAATCAGTGGGAAACAGTTGAAAGCTTTTTCACTAAGAT


 


CCAGTGCAAGCACAAATGCCCACTTTTGCTACTTCTATTCCACATAATAT


 


TGGAAGTACTAGCAATAGCAATCAGACCAGAGAAAGAAATAAAAAGCATT


 


TAAGTCAGAAAGAAGAAAAAGTAAAATTATCTCTATTTGCAGATGATATA


 


ATCCCTTATGTAGAAAACCCTAAAGATTCCACAAAAAACTGACAGAATGA


 


TTAATTCAGTAAACTTGCAGGATACAAAATCAACATACAAAAATCAGTAG


 


CATTTTTATACACTAATAACAACATATCTGAAAGACGCTTTAAATCCCAT


 


TTATGAAAGCATAAAAATAGTTAGAAATAAATTTAACCATAAAGGTGAAA


 


TATTTGTATACCGATAACTATAAACCTTTGATAAAAAAAGTTGAAGAAGA


 


CACATATAAATAGAATAATATTCTGTGTTCATGAATCAAAAAATTTAACA


 


ATGTTAAAATGTCTGTATTAACCAAAGCAATATACAAATTCAATGCAATT


 


TCTATCAAAATTTCAAGGATATGCATCACAGAAATAGAAAAAAAATTCTT


 


GAAATTCATATGGAACCACAGACACATAAAAACAGAATAGGCAAAGGAAC


 


AATGAGAAAGCAAAACAAAGCTTGAGGCATCACACTTCCTAAGTTAAAAT


 


TATATTGCAAAGCTACAGTAATCAAAAACAGTATACAAATGGCATGAAAA


 


CGAAAATGTGGACCAACGGAACAGAATATAGAGAGCCAGAAACTTAACTA


 


ATTTTCAACAAGGGTACCAACAGGACACCCTGAAGTAAAGATAGTTTCTT


 


CAATAATGATTCTGGGAATTGGATTGCACATGCAGAAGAATGAAATTGGA


 


CCCTAATCTTGCACCATATACAAAAATGGACTCAAAATAGATAGGAGACC


 


TAAATGTAAGATGTGAAACCATAAAACTCCTAGAGAAGAACATAGGGGGA


 


AAAATTCCTTGATATTGGCCTTGGAGATGATTTTTGGATATCACACCAAA


 


AGCTTAGGCTACAGAATCGAAAATAAATAAATGGAACTACATCAAACTAC


 


AAAGTGTCTGCACAGTAAAGGAATCAATCAACCAAATAAAAAGGCAACAT


 


ACAGACTGGGAAATATATTTTCACACAGCATATCTCCTAAGAGGCTAATA


 


TTCAACATTTGTAAAGAACACTTACAAATGAGTAACAGAAACAACAAACA


 


GCTTGATTAAAAACAGGCAAGGGACCTGAACATACTTTTCTCCAAAGGAG


 


AAATAATGGCTAACAGGATATGAAAAGGTATACAACATTGCTAATCATTA


 


GGGAAACACAAATGAAAACCACTATGAGATATCACCCTTCACCCATTAGG


 


ATGGCTATTATAAAAAAAAAAAAAGACAAGA


 


Human Genome Map Xp11.3 (2100 bp sequence)


(SEQ ID No. 72)


39A


AGTAAGTGGTGGAGCCAAGAATTGAACCACAATGTTCAGGATTCATAGAA


 


TGATTAGAATATAGTGAAAACAAAGCAAGAGATAAATTAGAGAGCTGGCA


 


GGCGGGGCCCACTCATGAGAGATGCATGTGTACGCCATGTAGGATACCCA


 


GGTTTTCTTCTTTTGGTGAACGGAATCTCTTGAAGGGTGTTGAGCAAGAC


 


AGCAATATGAGCAGAGAGTTAGAAGCCCCACCACTCAGGAAGCAATGCAG


 


AGGTAGGCACGGGAGTGCATCTGAGATGAAGAGAATGGGCTGAGGTTGCA


 


GCTCAGAGGCATAAACTAGAATTGAATGTGCTGGGCCTCGGATGGACTCT


 


AAGCCTCTTGTTGAGTGTTAGGGAGACAGGGCCATCATGGAAGCCAGCTT


 


TGGACAGCAGGAGGGACACCTTTTCTACCGAGATGAAAAAGGAATGGCAA


 


GTTGTGGATGTGGGGGCATGGGTGTGGTTTACATCTCAGGATCTCTATAT


 


GCTCTATTAACCTGQAGATGAGGTTTTCTGTTATAAATTGGAGGAAAATG


 


GTGAAGTTAGGAGCTTAAGAGTGAGAAAGTCTGAAATATCCATTGTGGAG


 


AGTGGAAACAGGTACAACTAGGCCTTGATTCCCTCCTTAACTGCTTCTTC


 


ATCCTCAGCTACTCACTGATCCATCAGTTGTCCAGTTTGTCATCTGTGAC


 


TTTGATTTCTATTGGCCCTTTCCTTTTGGACCTTATTGGTCCTTTCCTTT


 


CAGCATATAGAATGTTCATGTCTCTCTCAACTTAAAACAACAGCAAAACC


 


CAGCCCATGACCTTCTGCCCGGTAAAGTCATCCTGGTAGTGTCCACCAGC


 


CTGGCAGAACCTGTCTTCCACAGCAGCCTGGTGACAACAAGAAGCCACAG


 


CAGCAGTGTTTGGCAGTGGTCTGGCCCTCTCCAGACAAAATAAGCATCCC


 


TGGGGTTCCTGGACAATGAAGGGCAAAGGAAAAGAGAACAGGTCTCAAGA


 


ATATACTGACATCTCCAAGAGGAATTCAAGATAATATGGCAAATGGGAAT


 


TAAATGAGAAAGTAAAAGAGAGGTGACCATATGCAATCTGGAGCAGGTGG


 


AATGTGTCATGATGGTTCAAGGGCAATCAAGAGTTCACATTTATGGTGAG


 


GATTTCTCTTGATTTTTTTTCCTCCTGTCATCTTATTTTGTGTTTTCAGT


 


TTTTCATGTATTGTTACCATTACCTTATATTGATTGCTTCTTGTCTTTTG


 


CAATACATCCTAAATATAGCAGGTTCTTGAATAACATCACCTCGTTCAAC


 


ATCATTTTATGATAATGTTGATGGGGAAAAAAAAATGGCTCCAGGCTGGA


 


GCCACTGTCTGCATGAAGTTTGTACTTTCTCTCCATGTCTGCGTGGGTTT


 


TCTCTGGTTTCTTCTCACATCCCAAAGCTGTGCACATGAGGTGAGCTGGC


 


ATGTCTATATGGTCCCAGTGTGACTGAGTGTGGATGTGTGAGTGCACCCT


 


GCGATGGGATGGTGTCCTGTCCAGGGCTGGTTCCCACCTTGTACCCTGAG


 


CTGCTGGGACAGGCTCCAGCCACCCATGACCTTGAACTGGAATAAGCACA


 


TTGGAAAATGAATGAACAAATGAATACAAATTAGGATAAAATAAAAACTC


 


ATCAAGTCTATGACAATAAAGGACATGGGACAAAAGCGCTCAGCAAGCCT


 


GCTCTACTTGTGATTTTTTGGTTTTGAACTGCAAGGTGGGAAAAGATGCT


 


CCTTACAATGTTCGCTCTGCAAACATTTATTCCCTGATTTAACCCATCAC


 


TACCATGGCCACTGCCACTCACTGATTCACCAATTGGGTAAATCATTGTC


 


TTGTTTTTATTAATTTTTTTTTTTGAGACAGAGTTTTACTCTTGTTGCCC


 


AGGCTGGAGTGCAATGGTGTGATCTCAGCTCACTGTAACCTCCGCCTCCC


 


GGGTTTAAGCGATTCTCCTGCCTCAGTCTCCCGAGTAGCTGGAATTACAG


 


GCGCCCGCCACCACACCCAGCTAATTTTTTGTATTTTTCGTAGAGATGGG


 


GTTTCACCATGTTGGCCAGGCTGGTCTCGAACTCCTGACCTTAGG


 


Human Genome Map 11p15 (2100 bp sequence)


(SEQ ID No. 73)


40A


AAAGGCTTCCTTCCCTCAACAAAAAGGATCTCACCATTCTTTATATTCCA


 


GGTTTACTTTCTGATTTACCCGTACAGTATCATAGCCTGGAGGCTCCTGA


 


GATGCATTCTTTTTTGGAAGGGGCCTGATTTTGAAGTCTGACTCAGCCAC


 


TGATTAGTGAGCAGGCTTTCCTAAATCTTCCTTTCCTCTCTAGTAAAGTA


 


GGTCAGATCGTAATCTCTTCCTCACAGGACCATTGTGCAAATTAAAGGAG


 


ATAACGTGAATGGTTTGGTAGCAACTCAATGAATGTATCTGAATCCTCCC


 


GTCAATTTACTCTGCTGTCCATTATAGTCAGTTATGTATCTGTTTTATCC


 


TGTCTGGTCGAGAATGGAATCTGAGGACCAAAACTCCTCTCTTACTCATC


 


TCTGTGCATTTTCCTCTTTGCCCCTGCCCCTTCCTCCAACCCAGTACCTA


 


GCATGGTTTCTTCATTTATGTGTAAATTTTATCAAAGTGGTGTCAGTCTG


 


TGCAAATCATCTGCTGAAGTCTGTTAAGAACGTTCAGCAATATACACTTC


 


AACAGTAACAGGGACAGTGTGGAAAACCCTTGTTTTCTTCCTACTCTCCA


 


ATTCTTCTGCCTCTTTCCACTGCTTTGGAGAGGAGGTTACAATCAGAGTC


 


ATTTCACCATAAGAAAATCATCAATTTTCTAATGAAAACCCCCCTCCTTA


 


AATATTCAGCCGTGGCACAATCCCTAAAGGAGAGAACACATTAATGCAAT


 


GCACTTGGCCAATTTGTGAGCCCTGACTTGTTGAGCACAGACTCTTCCCT


 


GACCCTGGAAGACAATCGGCAGGACCCCTGAATAATGAAGTATGAATGCT


 


CACCATTGTGCTATCTCTAGCTACACCAGCTTCTACCTAATCTTTTTTTT


 


CCTTTTCATTGCTCTCCTTTGCAACTTCCTAAGGATTTGGCCATTTTCCA


 


CTGTGTCCAACCTACGAAGCTGTAAATACCTGACTGAGAAACACAAAATG


 


TGTTTATAGGACTTCTGATGGCTTCTCATCTAAACCATAAATGTGAAATG


 


CATTTCAACATTTCTCAGAAAACACCCCATCCCCCAGATTCAATTGGCAG


 


CACAAATTTACTTCTCAGAAGACAGCACCAAAATCTCAACATTGGCATT


 


TTGAATCAAGCACACACACGCAGCTGCATTGTGTTAACAAAGTGAAACAT


 


TATTAGGTCGCATACTCTGAGTGACAATATCCTCGAATGATCATTTCTGT


 


GAGAAATTATTAGCTATGAGAAATTCAATTTGGTAGCATTTGGGCATTAC


 


AGACAGCTAGTCTGTTTATATCAGCAAGGCTTTGATGTTAAGACTGTGTA


 


ACTGCAGCCACAGGAAAAGCAGACTGAATACAGGGTGGATAAGGTCACAG


 


ATATAAAAATCAGATAGAGTTCTGTTCTATTATCTACATAGTGTGTACTT


 


TGGGAAGTTACTTAATATTTCTAAGCCTCAGTTTCCTCATAAAAATAAAA


 


ATGGCAAGCAATATGAAAACTATCTAATAGAATATTTGTGACACTAAATT


 


GTAATAATGTATATAAATCACTTAGCCTAGTATGTGGCATTTATTAACAC


 


TCAAGCAJAGTGTAATTTTTTAAAAAAACTCTTATATCCCTTACATGACA


 


GAAATATTAAGACCAAAAATGGTTACTGAGCCCTCAAAGGTATTATCTCA


 


TTCTGGCTGAGCTATCTGGACCTGGAGA4AGTCTAGAAAAGACTCTATTT


 


CACTCCAAGTTTCTTGACCCTATCTTTATTTTTTATCTTCTATCCACTAG


 


GACCTGTGATCAGGCCAGGATTAACCAGTGTTCTCTAGGATTAACGTTTT


 


TGGCAGCTGGGGATGATTGCCTAAGATAATTGTTTTTGTGTCTGCCTCTC


 


CTGCTAGAATGCAAACTCTCAAGGGCAGGACATATGTCTTTCTTTATCCT


 


ACCTGTTAGTGATCAACAGGAGAAGGCCACTGCTTAACTGTTAGTGTCAG


 


GTCAGCTCCAAGCTGGTACTTCTTAGGAACTCTTTTCTTTTCTTTTTCTT


 


TTTCCTTCCTTCCTTCCATTTCTTTCTCTTTCTTCCTTCCTTCCTTCTGT


 


Human Genome Map 2q31 (2100 bp sequence)


(SEQ ID No. 74)


41A


CACGTGAGGACACAGCATAATAGTAGCCACCTGCAAGCAAAGGAGAGAGG


 


CCCAGGAGAAACAAGCCCTGCCAGCACCTTACTTAATCTTAGACTTCCAG


 


CCTCCAGAATTGTGAGAAAATAAATTTCTGTTGTTTAAGCTATCCAGCCT


 


GTGATATTTTGTTATGGCAGCCCCAATAACTAGTATGTGTATAATGAAGC


 


CCTAGACAACAAGGGACTCTCATTTCTCCGCATATTTGTAGAACTCATCC


 


CAATTATATAGAGCTCCTACTCTGAGTGCTAGACACAGTGTTAAACACTT


 


TCCCTGTGTTATCTCGTTTAACCATTAAGCTGAATCCTCCAAAACCCTTT


 


GGAAATCAGACTTATCTAAGAAACTCACTATTGTAGTGAAGCTGTTTTAA


 


AGAAGAATTGAAGGTATTTTTCTTTATCTTATAATCTGTTACATTGTGTT


 


ACATTTTAAGATAATACTAATCTAAGGACTGATAACAATTTAATTTGCCA


 


GAATCATTAAACCAAATAACATCTTTAACAGTGGCTGCTAGACAGGGGCA


 


GCTGTATATTTTAATGCCATATTTGGGGGAAAAAAAACAGGGTAGCAAAC


 


ATATCTATAAATAAGAATTAATTGCTACAAATTACCTGGGAAGGGAAAAA


 


TGTCAAGTTCATATAAAGAATATTATTGACCCATGGATTTACAGCTATAT


 


AATAATTTGGTACCTGGTTTATTTCTTAAAGACCTAGCACGTTTCTTGTT


 


TTCTCCTGCTATATTACGTGTACATGGCGTTTCAATAATCAAGCAAAAAA


 


GATGTATGCACTATCTTAGTCTTTGTTGTCTAATTAAAACTTTTTATGCA


 


TAGCAATTGCTTACCATTTTGCATTATCACCAGAGCTCATTTCTCATGGA


 


AAAAAAATTAGCATCAGTTTAAAAGAATATTTCTTTAATCAACAGTTCTG


 


ATTGTCAGTAGTACCATTTTGTAGATAGTTTTTAGCTGACTAACAAATCT


 


TTTATTTTATTGGCTGTCTCATTTTGCTCTCTTGCATATTTCACATTTAT


 


GTCTATTCAGACATTCTCCTGTTTTGTTAAGTGGAAATCTGTGTGGTCT


 


TTGATGTAAGACATAATTTATTTGACAAGGAAATATGAGTCTGTGCCCTG


 


AATCCACATTTAACTGATGGATTGAGAAATTTTAAAATTGCAACAAGATA


 


GACTCTCCTCCAGATTGCCGTACTACTTGCATTTTGCTTATCTATTTGGG


 


AGTGAATTTACATATGTGTGTCTATATACGAATATATAGAGAGTCATACA


 


ACCATGCAGCTGTACTTGTGCAATTTTTCTACTTTGTTAATAGAAAATGC


 


AGTCTCATTTTGTTAGTCATTAATGGTTCCTATAGAAAATTTTTAAAGAA


 


TTTTTTTCTGAAATTAAATTCAAGATACTTATTATGTTTTATCTTCATAT


 


AGATAGCTTTATAAAGAGAGTGATGTCTTCAAGTCTGTACTGCTCGCTTC


 


TCAGCCTAGTAAATGGAAGTTTTGTTAGCATTTCAAGATTTATATATTTC


 


ATATGTTCTCCCAAGTCTATGGCCCAGTTCTCTGTAATGGAAACTTACTT


 


TCAGCTCATTCCCTCTGCTCAGACTACTTGTCAATTAACCTTTGCAAAAT


 


GATAGTTTTAAAAAATATGACTTTCATATTTCAATCATGTTCATTTTCAA


 


TCATCTCAAAATGTAGAAATTGAATAACACCCGGGGTTCTACAGTGCTTT


 


TTACATATCATTTAAGGTTTAAAACATCTCTTTGATGTTCAAATATGACT


 


GCCATTTATATTCAATGGATGAGATTAAGTGGTTAAAATTACTTGTACTG


 


GGCATGCCCCTGCTTTGTTTATAGGTATGAACAAAACACTAAGGATTTTT


 


CATAAATATGCACCATTTCCATTGATGTTTTTGACTGCTGTCTGTGACAC


 


ACTAGGTAGGCCATATTAAGTAATGGGGAAGAAATCATAGGTCCTACTGT


 


GATATTAAAAATTTACATTTTGATGAATTAAATAGAGTTGTTGACCATTC


 


TACACTGTTGATTATATGAAGGGAAAAAGCTAACAACTTCTAAGAATAA


 


Human Genome Map 3p12.3 (2040 bp sequence)


(SEQ ID No. 75)


42A


AAAGGTAAAAGAGAGAAGCACAGAGACACTAAATGTATAAGTAATTATTC


 


ATTTAGTTTTGTAAGTGTCCTGGTTTGCATTTCAGGAAAGAACAAAATCT


 


ATCAATCGACATTTTTGTGCCTATTACAATTGTCCCTCAGTATACTTGGT


 


GTATCGGTTCCAGGACTACCTGTTTATACCCAAATCCAGGCACATTCAAG


 


TCCTGCAGCTGGCCCTGCAGAACCTTCATATGTGAAAAGTTGGCCCTCTG


 


TATACACGTGTTTTAGATCCTACAAATATTGTATTTTAGATCAGAGCTTG


 


TTTGAAAACAGTTTGTGTATAAGTGGACTCTTGCAGTTCCAACCCATGCT


 


GTTCAAGTGCTGACTGTACTCTCAAGCTAGTTCACATTTTCTAATTTAAT


 


CCTCAAAACGATGCCTTGAGGAAAAATAATAATGACAGAAGATGCAGAGA


 


GAGGGCACTGAAGCTTGTCCAAGTTTACAAATAGGGTCTCCATGCAAGTG


 


TTCACAATTTTCATCTTTTAATTTCAAAACCAGTGATTTTCCCCCCTACT


 


TTTACCCACATATAATAATAAATTTTAGGGTTTAATTCATTTTCTTGTATT


 


ATATTTTCATCCTATAGTTCTCCATTTTAACCCTAAAATTACAGAAATATT


 


TCCTGTGGCTGAAAGAAATTAGTTAGAAACTCTTAGGTATTTTAAGTAAG


 


AAGAATGCTACATGCAAAAAGTAAAGTCTGAAGAATGTATTTCAACCTTG


 


AAAAAAAAACCCTCAGACTCAGTCTGCAGTAAAGTTCATTCAACATTAAG


 


AAGCAGAAGCTATTTAAAGAGTTTAATGCAGAACACGGTAGAAAAGATGC


 


CCATTGCCAAGTCCTTCACGGCTCACCATAAATGTGAACAGCAAAGTGCT


 


ATCCATTTTAAAAATCAATCAAGGTGATGCAGTGCTTAAAATGCAATTGA


 


TTTTGGCTAATTTGCAAGTAGAAAGGTTTAGAACTTGAATAATTTCTTTC


 


CCACTTTAGCTGGTTCAACAGCCTACTCAATGAGTTGCCTAATTATTAGT


 


CTTGTTTTTTTTTTTTTTTTCATTTATTTACTTTAGACAATTCCTGAGTG


 


AGACAACTTTTGATTTATTTCAACTGGCTTTGGGTAGATGAAAGAGACCA


 


CAAACCAAACCAAACCAAAACAAAACAAAACAAAAAGCCACCAGGCAGGC


 


CAAGCACGATGAAGAAAAACTTCAAATGCAAGAACTATAATTTTCAAACT


 


GTGAGTTTGGAATTCTTAAAAAGCAAAAACCATTAAGTGACTCCATTTCA


 


GCTACCTATTAGTGATCAGGTTGAAAAACAATGAGAAAAAATGGAAAGAA


 


AATCACTGCAAATTCCATTGGGGTAGATTAGAAAGATGTTAAATTACTCT


 


TTTTATCTGCCTTCTCTGATTAGGAAGCCTAAAGAGCTTACCACCTTTCC


 


AAGGAGTCAGCATGTCACTTTAATGTTTTGCTGCTGTTGTTTGGTTGATT


 


GCTGTATATATATATATATACATATATATATATATATATATATATATATA


 


TATATACATATATATATATATATATATATATATATATATATATATATATA


 


TATATATATATGTATTCTTGCTCTGTCACCCAGGCTGGAGTGCAGTGGTG


 


TGATCTTGGCTCACTGCAACCTCCACCTACTAGGCTCAAGTGATCTTCCC


 


ACTTCAGCCTCTCAAGTAGTGGGGACCACAGGCACACATCACCATGTTGG


 


GTTTGTTTGTTTGTTTGTTTTTTGTATTTTTAGTAGACACAGGGTCTTGC


 


CATGTTGGCCAGGCTGGTCTCAAACTCCTAAACTCAAGTAATCTGCCCAC


 


CTCAGCCTCCCAAAGTGCTGGAATTACAAGAGTGAGTCACTGTGCCCGGC


 


CTTTAGTGTTCTTTTAAATAGCATTCATAATCTTTTAAAATATGTTTTAC


 


AAATGAAACATTGTGTTTGAGTGACATGATGGGGAAGGAGCCTGCAGTCC


 


ACAACGTCTCTGGCTTCCTTTCTTGCATTTTCTCAG


 


Human Genome Map 4q13.3 (2040 bp sequence)


(SEQ ID No. 76)


43A


CTCAGTTTTAAATGTTTCCATCAATCAGTAATTCAGCTCCAGAGTTGCCA


 


TAGAAGGTTATGGGAAAAAAATCCTTCTGCTTTTCCAATATCAAAGAGAG


 


AGATGTTCTGGAAGGTTTTATTTTTGCCACCCTGTTTCTAATGCATTTCG


 


CCTTAAGAATAATATTACTCATCTCCAGCAATCAGGCTCAAGGAGGAAAT


 


TTGATACCATTCTGTGGGTCATCCCCAGATCTCTGCAGGCTTCTGGCAGA


 


TGTATGATGTAGTGGGCACCACTAACTTTGTCTGCTAGGGTATTAGTAGG


 


ACGTGGTCTACTGAATACCGGACAGACATTTGGAAATTAAACTAATCAAA


 


ATAGGCTAATTTCACGTGCTAAGCAATGCAATTTCCCTGAATTTGTAGTT


 


CCATGATCTACTTTTTCTTCTACATTTCTCTTACTCCCTCTCTTCTCCGT


 


TTACAACACAAAATTCAACAAACTGCTAACTCTAGCTATTAATATCCCAT


 


AGTATTTCTCTAAGCAGCTTCATAGTCACAGTTTCAGTTAAGGCTCTAGG


 


GCTTTCATTCCTGAACTACGTGTACTACAGATCCCAGTTAAAATCTCTAT


 


CCTTCCCACAACAGTGGTTGACCACCTTCCTCAACATTGGATTTGGGGTG


 


ATAATGACAACATTCTGAACAAAGCTCATTTTTTCCCCTAACCCCCAGCT


 


AAATAGAAGAAATGTTAATGTTACTCCTCTTTAGATTTTTTTAATTAAGA


 


ATATTTTTAAAGGATTTTTTTATGATTTAATGGGACACAATGAAAAGATA


 


TTTTGACAAAGGTAAACATCTGAAACTGAGGCAAAGAATTTTAGATGTTG


 


CCTGTGTAACCATTATTCCATGATCAAAAGCCCAATGTTTAACATATCCT


 


GATTTCATCATTAAACAAGCATAAGAAAAAAAAAAAAGAAAACCATAAAA


 


GTGAAATAGATTACATCTTGTAATAATACAGCTATGAAATTCTGACCAGA


 


ATGAAAATATGAGTATGAAGAGAGTAATCATTTGCTTATTAATTCAAGGA


 


ACAATTTGCCATTTTTCAAGTATTATGAAAATAAGAGACTGTTGGACTCT


 


TTTTAAACACGCAGGTTTTTCAAATGTATGTACAGTAATATTATAGCTCT


 


GGTGAAAATTTTGATGAAAACAAAATTTTCTGTCTTCTTTTACTTACCTT


 


GCCCTTTTCAAAAAATAGTGCTTAATGTTAACCAATGGACAGTCTAACTA


 


CCTGAAGCTTTTCATTCAGCTTTATTTTCTCAGCAACTATGGTTGAAACT


 


GACAAGTTAGGTGAAAGGTTGTGTAAGTATCCAGGCAGGGGCAAAAATAT


 


CGAGTTATCCCCAAATACTAACAAGCACATAGGTAGAATATTTCTACCAA


 


GTTAAAGAGAATAAAGGAACCACATTGAGCAGAGCTACCTTATTCAAGGA


 


CCTCATTATCTCAAGGCACCCCAATTGAATAAGTGTACCATTATTCCCTT


 


CGTTCTGTGCAAACAGCAGACGTAGAGCACAAAGAGAGACGATTTCAGTG


 


AATCACACTGTAATTATAAATGCCACATTAAAAAACGGAACAAAAGCAAC


 


AGCAGGACACTGTAACGTCGATGGTTAAGGAGGGCAAACAGAGAAACATT


 


CTCAAAGGCCACAATAAATTACATGATCCAGTTCTTTGTTACAGGCAAAT


 


TATTGGACAATAAGAGAGACACTGAACACAACTTATCAGTGGTAAAGTAA


 


CTTGCACACATTCTCCTACCACTGAAATATTCCTGTTACCTACACAACTG


 


CATTTGTATATACAAGCAAGAATTTTGATGCACTAAGTAATTAATATAGC


 


TCTCTAGTATTTTTTTTACCTCTGTGCTTATTCTATCTGGGCAAGGTGTG


 


GTAATAGCACCTTAAAAAATAAGATCAGATTTAGGAGTGAAGAACACTGC


 


ATTGGAAAAGGTAATTGCTAATTTTATTGTATTTTAATTATTTGACCATT


 


TGTGCACAAAATTAAATAATACTTGCTTCATCTCTATATT


 


Human Genome Map 4q13.3 (2160 bp sequence)


(SEQ ID No. 77)


44A


GTGTATTGCTGTGAAAAAAGTCACTTCAAATTTAGTAGCTTCAACCAACA


 


ATCATTTTATTTGCTACCAATTTTTTGGGTGAGAAGTTTGTGCTGGGCTC


 


AGTTGGACAGTTCTACTGATTTCCCTGTATATACCTCATGCAGCAAAAGT


 


CATCCTGGTGGTTCTATGTGATGGTTAATTTTTGTATCGACTTGGCTGGA


 


TGATAGTCCCCAGATATTTGGTCAAACGTCATTCTAAATATTTCTGTCTA


 


TGTGTTTTGGGAATGAGATAATATTTTACTGGATTATTCTTCACAATGCG


 


GGTGGGCCTCATCCAGTTAGTTGAAGGCCTTAATAGACAATAATTGACAT


 


CAGACCTAAGTAAGAAGGAATTCTGCCAGCAGACTGCTTTTGGACTCAAA


 


TTGCAACTCTTCCCTGAGTCTCAAGCCTGCTGGCCTACCTTGCATATTTT


 


GGACTTACCAAGCTTCCACGACTGTATGAAGCATTTCCTTAAAATAAATG


 


TACATATCTGTCTCTCTACACACATACATATATACACACTCTCACACACA


 


TCCTGTTGGTTCTCTTTCTCTGGAGAACCCTAACACACTCCACTCAGACA


 


GATTGTCTAAGGTGGCTTCACTTAAGTTTTGGATATCGACTCTTGCCGTC


 


ACTCTCTTGAAACAATGTTCTTAGACTCTCATGTAAAGAAACTCCATCTA


 


GCTGCACCCTCGGCACTGTCCCAAAAAAGTGAGGATAATACCTGCAAGGT


 


TTCTTAAGGATTATGCCTTGAAGTCATATTTTACTTCTGTAGAGTTCTAT


 


TAGATCAAACAAGTTACCTGGCCAAGCCTAGGGTCATAGTGGGAGAATTT


 


TGAGGGCCATATGGCAAACAGCCCACCATACAATACATTCTCAAATGGCT


 


TCTCAAATTTTACATTCTTGTGAATGATTCTCTCTTCTTGTGATTAATTT


 


TACACACATTACTTCAATATAAATTTTTATCTCATTGCATTTTCAGTTTT


 


TTTGTAATTTCACATTTATGGTACTCTTACAATGTGCCATGTGCTATTCT


 


AAGTATTTTATGTAGATTAATTTAATTCTTACAACAACCTTTTGAGGTAG


 


GTAATACTATTTTGTTCCCATTTTCAGATGAAAATGCCAAGGCATAGAAA


 


GCTTATGTAACTTGCCCAGTAACACTCAGAGACTTAATGTCACAACCAGT


 


ACTTAAATGTATACTATCTGACTACAGGGTATGCATGCTTAGTCATAATG


 


TTATTAAAATATCATTTGTGATGACTGAGGCATCATGGCAGATAGGAGGC


 


AGGACTAGATTGCAGTTCCAGACAGAGCAGGAGACAGAGGCTTGCACATT


 


GAATTTTAGCTCCAGATCGACTGCAAGAGCAAACCGGTAATCCTGAGAGG


 


ACCCACAGATCCTCTGCCGGAAGCAGACTGTTTCTGCAGGACCAAGGAGA


 


CACCACAGATACTGTGGGTGTCCCAACTGCAGAAATTGGAAAGGGAGACC


 


CTTCTCTTCCAAACACACACCCCACTGGAGAAGCTGTTTCTGACTTTACC


 


TGGAGCTGAGTCAAGTTAGAGAGCTGAGCCAAGTGAAATACAGGGGTAGG


 


GGAAGTAGCGGAAAGACCCTGGGAGCTCGCTGGGTCCCCCAAGCAGCCCA


 


TACCTGCCTGGCACCACAGGGATCCACTGGGAGGTTGGCCAGAGAAGTAG


 


GGGGTAAAATACCACAGGCAGAAGGAATTCTCTAGCTAAACTCTGTAACA


 


ATTTGAACGGGGCATGAAGCCTCCTGGCCAGTACTTCAAGGAGGGTGTGA


 


ATCCAGCATGCAGACCTCACAGGCAGGGGGGAAAACTAAAGCCCTTTTCT


 


TTGGCAGCCGGGAGGTGGAAAGCCTCAGGCAAGTTTTCAAGCAGGGCTCA


 


CCCTCCACCTGGAAACAGACTCCAGGTTGTTGAGGGGGACACGGTGGGAG


 


TGAGACTGGCCCTTCAGCTAGCATGTGAACTAGGTGAGGCCTGTGACTGC


 


TGGCTTTCCCCTACTTACCTGACAACCTACATGACTCAGCAGAGGCAGCC


 


GTACTTCTCCTAGTGTGTCCGGAATTGGTGGGTTCTTGGTCTCGCTGTCT


 


TCAAGGATGAAGCCGCGGACCCTCACGGTGAGTGTTACAGTTCTTAAAGA


 


TGGTGTGTCCG


 


Human Genome Map 1p14 (2100 bp sequence)


(SEQ ID No. 78)


45A


CCTCCCACAAGGTCCAACTCAATCAGAACCAAAAGGGAGATCACAGCATA


 


TCCATGCAATCCCTGGCTGGACAGACGGGGCACCCTAGGGCCTGGAGTTA


 


CGCAGCTGACTGGCAGAGGTCAGTACCCAGTTCTACCCAGTGTGGCCACC


 


CGATCCAACTCTGTGACTCATTTTAAATCATAAGTAGTTTGAACAAAGAC


 


TTAAAATTAACGGGTTTGGTCATCATTAAAGTTTATTTTTAAACGTCAAG


 


TAATTTGGCATTTTACTAACAACAACTTGAGGATATCCACAGTGTATGAA


 


ACACCAACTCTTGTTTCAATAAAAGTCTAATGAAAGTTTCTCAAATTCTG


 


AAACCTAATTCCAGGATTCTTATTTGGAACTGTTTTTTTGTTTTTGTTTT


 


TGTTTTTGTTTTATCAGAGTACATTAACTCAGGGGGAAAATGAGATTATC


 


TTTTGATTCAGAGAGAAACAGAACATTCCACTGATAGTTTAAAAATAACA


 


CAGTGACCACAGATAACTGTAGTTCAGCAATTTTCAAATTCAGATTCTGG


 


GTCAGGGCACAAGATTATGCGTCTTTAACAAGCACAACTGATTATAATGC


 


TGATGGTCTAGAGGAAACTTGATGGGAAACACTGATCTATTCAACACTTT


 


TTAAAAGTACACTTTAGTACTATTTCTACCTAGTCAATAAAATAAAGAAG


 


GAAGGAGAAAGGAGGACGAATAAGAGAGAATCCGAAAGACACACTACCCA


 


GACAGACTACTCAGACAGACGAGACAGTCAGGCAGACATGGTGCTACCCG


 


TCAAGCATGCAGGAAAGCAGCTTTCATGGAATAACATTCCTAAACTCTTG


 


CCTAATAAATTATGCTGAGAGCTGCTGCTAAGAATTTTTTAAACCAACTC


 


AAAGCAAAAAAGGAGCTATTCACCCAATCAACAGGTGAAATCAAGTCACA


 


GACTAGTATAGGGTTTGGCAGATTTCAGGCCCTCCAGAAATATCTGTTTA


 


ATTGAGAAGCAACTCCAGCTCTAGCTAGAAATCTATTTAACCATAAAAGT


 


GAAATCATAATGAATTTGGTCGTATCTTATTTTTCCCCTTTGTTTGTTTC


 


CTCGGGGCATCTATAATGGCTGAATTGGAAATGGAACCACAAGTATTATA


 


ACAACATTTGTTGGAAAGTTCATCCTGTATTTTAGTAGTACATAAGTTGA


 


CAGATATGGCTTTATGAATTGTTCTCAGAGACTTAAAAAAAAAAAACCCT


 


GAACTTTGTAAAAATTACATCCATTATCCAcCAAGTAACATTTGCAAGCA


 


AAACCCTCTACTAGAAAAAATGGGTGCGAAAATAGGAAAAGGAGAAGAAC


 


AGGAGGAAGAAAAGGAGAACAGGACGTACAATTAATTGAGGGGAAAAAAA


 


TCATGAGTAAAGAAGTCAGAAATAAATGTAGCTAAAAATACAAACTGCTA


 


CTTTATGGTCCAGATATTGTAATATATCATTTTTAACATAAAAGAAAAAC


 


AAATCCTCAACAGACTTCCTATAAACGAAATTATCAGAGTTCCCGAGTAC


 


ACCGGGGGTCGAGGGAAGAATCTCCATGTGCTCCGAGTATCGATAGCCAG


 


TCCAGCTTCATTCACTCATTCATTTCTTTTCTTTCATTTCAGGAGAACAT


 


TTAGCAGTGTTTTGTTTTATTTATTTTATTCAAAGGGAAATCCTCATGTG


 


ACACTAGCGGTGAAAATAACTTGTATTTGTAAGTTAATGTCTGCTGTACA


 


TCTGAGTACACAATTGTCTTTCACAGAAGATGGAGCAAAGTATTACGGAA


 


AGTTCATTGGCTTCTGAGTCTGAGAGAAATGGGTTCAAATCCTGAATACG


 


TTCCTTATCTGTGTGATCTTAAGACTCATCATTTAATATTCTGAGTCAGT


 


TTCCTCCTCTATAAAACAAGAATCAGACGGGGCACAGTGGCTCACGCCTG


 


TAATCTCAGCACTTTGTGAGGCCAAGACGGATGAATCATCTGAGGTTAGG


 


AGTTCGAGACCAGCCGGACTAACATGGGAAAACdCCCGTCTCTACTAAAA


 


ATACAAAATTAGCCGGGAATGGTGGTGTACGCCTGCAATCCCAGCTACT


 


Human Genome Map 2q22.1 (2040 bp sequence)


(SEQ ID No. 79)


47A


TTGATTCATGGGATGTTTATGTGGATAATTCCTTTGAAATCCAGCTTGAT


 


TTATGAACAATCTTCTCTGCTCTATTGAGCCATTAAATCCAGAGTATTAG


 


TGCATTTGGAATACACAGAGATGATAATGACATCCAAAGAAGAGTCCAGC


 


AAAACTTATTTCCATGAGGACTTTTTCAGAGGGATGAAGTAACATTAGCT


 


ATACAGGTTAGCATTATAAGACTTCCCAAGTGTAGATGAGAATAATGGCA


 


ACTCTGTGGTCCTAAGGATGAATATTGCTCTGGAATATGCATTTTACACT


 


ATATGAAAGAAATTAGGATCGATATAAGCTCACTTATCTTTGCCTTATTC


 


CTCCTCATGTTGTTTTTGTCTAGATTGTCTCAGCCACTTGTTTTATTTTA


 


CTTAAATTTTAATTTCATCTTATTGTAAACCTCCATTCCTTCAGAAACAG


 


GTCAAGAACATGTCAATCTACCTAAGTGAATAACTAATATTAACAATTAA


 


ATAATAAATAGTACTGAATGAATATACGAATACAAGAATAAATAAAAATA


 


AAATGTATTACTTCATCGATGGATTTCCTAGTAGATGGGGAAACGGTGAG


 


AGGATATGAGCTTCAATAAGAAAAATGGTGCAATAAGGCAGAAGCAAATG


 


CCCAAAACAAATCAACACATTCACAATTTTTCCAAGGACCTGTCATGTAT


 


ATATTTTTTTCTTTTTTTAACCATTTGTGGCCCCTTTTTTTAACCATTTG


 


TGGCCCCTTTCTTATATCTCATTTCTCTCTTTTGTAAGGCTTCTGTGTTA


 


ATTGACAGCATGTTCAGATATAAATCCATCACAGGAATGTGATGAAATTA


 


GCCATTCAGACCCCTGATATTAAGAAATTCAAAGAAATGGATAGAGTATC


 


CAACCAGTGAGGAATTAAAGAAGAAAGAAGAGAAAGAGAAGGAGAGAGAA


 


ACTAGCTGTAAAGTTGGGATGGGTCGGGGGTGGTGAAGAAAACCAATTAT


 


TCATTGAAGGTGCCAGAAGGAAAATTGATGGCATGAATCCATAGCTTCTC


 


ACCATAAAGGTGAATAATGACACAGACACTTAGATTGGGGAATGAGAAAA


 


AAAAGGTGCATGCAAGGTTCTTCTATTTATATCTGATTAAGATATGAAAA


 


GAAAATGAGAGACTGGATTACTAAAGAAAAATTCCAGACAGTTAAGCAAT


 


TTTAGGAATGATTCATTTTAAGATATGGCCATCAATTATTTATAAGGGTT


 


AATAAATAGATTTATAAGCAAGAGGTACATGGAATCTAGAAATACATAAA


 


TGCTCTTCAATTATTTACAGCTCTGACAGTCATAACACATGAACTACTAC


 


CAAAAACACCATTTACTTGACTTTAAAATTTGCACCATAAACTATAAATG


 


GACCAGTTATGGAGCATCAGCCATTTGTAATGTGCCATGCAATATTTAAC


 


ATCAACTAAATGTGTTTTCACTAGCTGCTGACCACTTGGATTAATTTAAT


 


AAGCATGCCTAGTGCCTAATGATTTATTTGTGGGTAAATGATCATAACTA


 


TTTAATGGCCTTAATATTACAGATGTAATTCTGAAATAAAATATCATAAC


 


TTGGATTTAGTACATCCAGTTAAATAACAAGCATCGACATTTTTAAAAAA


 


TAATAAAAACAGTGGCCAGAAAAAGAAATTAAAGCACTTGCTAGTCATAT


 


GTCCCCATAGGTTTCCAGCTTCATATTGGCTTTATTTCTTTTTTTCCTTT


 


CATTTAGGTCACCCATTAATTTTCTTTCTTCATTTGCACACCCTCTTCCA


 


TTTCCTGTACTATCTTTTGTTCTAATCCTCTAGTAATTCCCCAGTGAGCT


 


CTCAGCTTCCAAGGGCACTCTATTTCTATTAAGCATGGCAGTCAACAAGT


 


GGAAATAGTCCTTGGTTGTCCTGCTTTCTGGGTGAATAGCAGAGTCCCTT


 


TGCATCACCTCAAAGACTCTGATTCTCATGATCCTCAGTCTGGTGCTGAA


 


TTGTGCTTTTGCTCATCCACACACATCCCCTACC


 


Human Genome Map 11q24.2 (2100 bp sequence)


(SEQ ID No. 80)


48A


ACTCAGCAATGGGTAGCTATACTTGAGATAATAGGCGGGATTTTATGTGC


 


AGCAATGTAGAGGATGCAGGGGCCCAGGATGGGCTGCCAGGTCTTCCAGA


 


GAGTGCTAAGGTATCCACCAAGGATCATGAATGTGAACAAGATAATGAAT


 


CACTGTCTACTTACTCTTTTGGAAAAGCTTCCATATCTCTGCCAATTGAA


 


TCACACTATAACCAGTCCCAGGCAATTCAGGATGACAAGTTCCACTTCGA


 


ACAGTTCTGGGAGTCATCCTGAGGGTCCCTGTGTATAGACATAAAAAGTT


 


CCATTTGTTCTTACACAGTGAAAATGACAGAACAAATATTATGGGGATTA


 


TGCCTGGGGAAAAAAAATCTGTCTCTGGATATTCCTGACACTATGGAGAG


 


AAAATCAGCAAAATTTAGAATCTTGGATCTCTTCCACTCACACTAGGATG


 


TTGTTTCTAGAAATCTCCCTGAAGTATGGTACTGACTCTTGGTGGTAAAA


 


GTGGAGAGGCTTAGAACTGAAATCTGGTCAGTAGAAGACTGAGGGTTAAA


 


AGTGGACGGTCAACCCATTGAATGAAGGCCTAGCAGGAAATAGAGAGACA


 


AAAATACAGGCATTAAGGGAATAATAGCTGAATAGTAATAATAATACATT


 


ATGTCAACAGCGGTGACAAAGGAAACACTCAATGTATTTATAGAGCTAAA


 


TAAACGGCAGATCTAGGTCCTACGTTTTGACTCTGAACAACCTTCTCGGT


 


TGGATTTTGCTTCTGCCTAAGGATTATTTTGGAAAGAGCTATTATTATCC


 


GTGATTTATCACGCTGCACTGGGGGGAACTCATACTTTCCACGGAGACAA


 


TTACTGAATTCTCACTGGAGGCGCTTAAAGGAGCCAGGACCTGTTCTGAG


 


GGTTCAGGTGGGAAAGGTGTGCCAGCAGGGGACTGCAGCCTGGCACCATG


 


GGACGTGTGTGCTGTTGACCACTTCTGTGCCCAGATCCCTCAGGCGCTTT


 


CTCATTAGATGCACCCTTCAATCTCCTGGTTATTGAAACAGGACTGGGGA


 


GAGGAGTTCACATTTATGGTGAGCCCATGCAAGAAGACCCTCCGACAGGT


 


GCCTGTCACCCCTGAGGAGTCACTGGTTGCAGCCCGTTCTGAAGTGTCAT


 


TGAGATAGAAACCAAGTCAAAGCCGTGGCCTAGAAAGAGAGTCTGGGCAG


 


AATTCTGCAAGCAGATTCTTTATTTGAGTAAGTATTCCTTGAAGAAGCCC


 


AGTTGTGCAGCTGTGTTTGGGTGGAGGTCATCAGAGGTTTAGAAAAAGAG


 


AGAAGTCATGGTTAATATTAGAAAAGAACTCTGAGAATCTGGAGGAAGGA


 


AAATGCATTACTAGTTCTAAGCAACAACTGTGGAATAAACAATGATAAAT


 


ACCGTATTAAATCTAAAGAGTTACGTTAATAGATAATAACAAGTAGGAGA


 


GCTAATAGCTAGCCATTAATACAGGCCAATTTATTATTTAAAACATTTAT


 


TAAGATTTAACAATAGTCAAATAATTTTTTTGTGAAACAGTTATTAAACT


 


GAATCTCTGCATACATTAATCAACTGATATTTATCATTCAGAATGTATCT


 


CATTATATCCAAAAGGGTGTGTGTATAGGCTTCAAAAACAAACTGGAAGA


 


TTTAAAATGAACTGTAGTTCATTTTTGCAAAGTGTAGATGTGTAAAGATT


 


ATTATGTTTGCCAGCTGGGTAGCCAGACAGTGAAGTGGACTTGTCTAATT


 


AGGAACAATCGCTGATAAATCAATTCTTTCCTTTTATAGGACAATTACAG


 


TTTGTGTGTATATGTGATTGTGTTTTAAATTCTAATTCGATTTTGTGCAT


 


TGTTCTGTAACCAAGTTAATTCTTTGAAGCCTTTTTAAATGGTACAAATT


 


TTCCATAAAATATAAATAGGTTTATTGCTGTTTTATCAGTCACGCAAATA


 


ATCCAAGATCCATCTATTCACATAATTCAGGCATTAACTGTGTATAATTA


 


CTCACATGAAGTCTTCAGTCTGGTTTACTATACGGAACCCCAAATATGAC


 


TTTAAATTGCTCCCCTCCTCTTTTCCTCTGTTATTTCTCTCCCTCTCTT


 


Human Genome Map 21q21 (2103 bp sequence)


(SEQ ID No. 81)


49A


TTGCATCATCTGACCTCTCTTCGAGTCCAAAGGACTGAGAACTAGAAGAA


 


CTACTGCTGTAAGTTCCAAAGTCCCAAGGCCCCTGAACTAAGATCTCCAA


 


TGTATGAGAGCAGGAAAAGATGGATATCCCAATTTAAGGAGAGAGAAAGA


 


GAAAATTTGCCCTTCTTGTTCTATTTAGATCCTCAAGGAATTGGAATGCC


 


CAACCACATTGGTGAGTGTGGGTCTTCTTTACTTATTCTACTGATTCAAA


 


TGTTAACAGATTCTGGAAACGTTCTCACAGATACACACAGAAATAATGTT


 


TTGCCAGCTCTCTGGGCAGCTCTTAGCCCAGTCAAGTTTACATATAAGAA


 


TAATCAACCCAGCTTTTTATAATCATCTTAGTATTTAATCAAGGAAATGA


 


TATCAGCTATCTACTACCACAAAAATAATTTTAAAAATTGGCTTATAAAA


 


GATGACTTAGTGGCCCTCAGCTGGGACAGCTTGTCACTATCCAACCAGCC


 


TTTAAATCCTTCCAAGAAGCAATCCTGGCTTGTTCTCCTGAAAACTGGGT


 


AGTTTTTCAAGAGATTGAGCAGAAGCATACAAGGCCTCCTGACACCTAGG


 


TGTGAGATGGGCACACAACCACTCCTGTCAAATTCTATTGGCCAAAGCAA


 


GTGACAAAGCCAATGCAGATTTAAGAGGTGGTGGAAAAAAACCCTAAAAA


 


TAGAAGTTGTTGAAAAGTCATATTTCAAAAGTCATTGGTATAAAGTAGTG


 


AAAAATTTGACATTTTTGCAATCAAGCTTATCAAACAATATTATCCCAAA


 


ATATAACAATACACTCAGTTTGCACACTTGTTTACCTTTTGCAAAACAGG


 


TAAGACAGTAGGACAAAGCAGGTGCTTTATGTTGTTTCAATCATTCAGGA


 


TTTGGACAGTTTGGATATTTTCTGTATCACTATAATTGATAAATACTCAG


 


ATGATTCTATAGTTAAGTTAGAATGGAAATTTTGGGTATAGTAACAAATA


 


CTACTTTAATTTAAACTTACATGTAAACAGTTTCCCTAAAGCAGTTAGAA


 


GTGTGACCATAAAAGTGAAATGGTTTAAATACATGCATTTACATCTGTCC


 


TAGAGTGATTAATGTAACTTTATTATAAAACTACTAATTTTGTGATTACA


 


TACACCCTTCCAAAGATACATTATACATTCCTATGTACACTCAAATATTA


 


TTTTTAAACTTCCATTCCAATCATTAAGTAGAAATGCATTTAAGAATCAT


 


GATTTTTTTAGAGTAAGTCTATAGGTGGTACTTTTATATTATAGATAACA


 


TTTCCTATACCCTTTCCACATAAACACAAGAACATTATGCTATAGATTGA


 


AAATTCCTGTAAACACTAAGCAGAGCTTTTGTACATAAACTTGTAAAAAC


 


TCTACATAAATGTATTCAGAAATACATGCTATTAAAATATTTTATTGTAT


 


ATTACTGTTTGGAAGTTTTCAGCTTAAATATTTTTATTTGATGATCAATA


 


AGATCTAGTATTAAATGGTCTTATTTATTAACCATTAAGTTAAATACATG


 


GAGAAATCCACTATGTCTTTTCCTCCAGCCTGTAAGTAACACAGGGTTGC


 


ATTTCTAATATTAACTAAGTTACATGTATTTTCCATTGAGAAGAGTGCTA


 


TCGAACTCATCCATGTTAATCACTCTTATGTGGAAAAGGCTAACATATAA


 


ATAAAAAAACTAGAAAATTTAAAAAAGGATAAAGAAAGAAGAAAAATGAA


 


CAGAATTTAACAGCAGTGCAACAGTAGTCTCTTCCTACCTTTCCTGGGCA


 


TCTTCCAATTTTATGGTGGTCTGATAAGCTTTCCAAAACACTTTGCTCAT


 


TTCCAGCACTGGACATTTACACTCAAGACTGCAGACTCGAGGAGTCACAC


 


ACTCAGCATCTTTTAGCTGTATGTTGTCAAGTTCAGACTACTCAAAGTGG


 


CATGTCTTTAAATTAGAATGTGTCAAGTGGGTCTAGTAACTGCACCGAAA


 


TATTTTAATAGTCATATTAATCATTAATAAGTCAGGAAACATGTTTTTCT


 


AATTTTCAGATCCCAATACACATGACTGATATGGTTTGCATCTGTGTCCC


 


TC


 


Human Genome Map 21q21 (2100 bp sequence)


(SEQ ID No. 82)


50A


AAGGTTTGGAAAGCTTAAGTCAAAATGTGTTGTTCATAAATACGGTCTGA


 


ATAATTTGAACATTTTCTGTTAATGGTATTTGTTCAACTATAATGATATT


 


TTCCAGCCAAGATATAATTGGCAATGTCAAAGTCACACACAGATGGGTAA


 


AATGGCCAATGTCTCTGGAAAATCTTGATAATAACTTTTTAGTATCTCTG


 


GTGCAAGGTCACTTAAATTCAGAAAATAGCACCCAAGGAAAAAATAGCCA


 


TATTCAAAAAAATAAGCTCCATATATTTAGATGTAGATATAAATTTGGGG


 


TGATTTATTTCTTATTAGACACTAATATTTTTTAAAACAGAGAATGACAA


 


ATAAGGAAATTTTGCAGTTAACTATGTCCTAATGAAAAAGGGTAGTAGTT


 


TTACAAGAAAGATATAATTCATCAAAAAGGCAGGGAAGCATTCAGACTAA


 


ACATTGAGTATGTTTGGAAATAATAAAAATTATTGTTTCTTTTACCAACA


 


TCAACAATCTTTTCAAATTAATTTATAAAACTGTCATCTCTGTTCACTAA


 


TTTTGAATTACTCATATTATTTTTAATTTTGAATACTTATAATATTACTT


 


ACTAATTTTTAATTAATTTTGATATACCTATATCACTGTTTTGAATTGAT


 


CTATGAATGATCTAGAAATGACTTTGCCTGTTTTTTTTTTTGACTCATGG


 


GTATTTACTTTTCATTAGGTAATTTTAATGTATTGTTAACTAGAAAAATA


 


AGATGAAGAAAAAAACATTTTAAATGCAAAATATAAATTTAAAGAACTTC


 


AAAAGAATAAAATTTCAGTTTTATGTCTTTCAAGTAAATTTGCTGTTTTC


 


AAAATTATTTTTTGTTACAAACCTATTTTATTTCAAAAAATATGCTATTG


 


TTTTTAACCTATAATTTTTAAATATCTGACAGCATTGTAGGACTTAAAGC


 


TATTAAATATATAAAGATATAATAGAACTTATTGGAAATATTCAAGGAAA


 


AACTAACATATTCTTTAAAAACATTTTAATTTTTAAATTCTATGTTAATT


 


GACTTTTTGATACATATTTTACTTTTCCTTCACTTCTTTTGTCAATTCTT


 


AAAAATGTCTTTCTTCATAATTTTTGGCAATTAGTTTTTACACTTTAATA


 


GCAAACATTGCCATAAAAGTGAAATTAAGCATTAATTAATTTTATGTCTG


 


CAGGCAGAGTGATTTCCTTAGGGAATCAATTTAATAGAGAGAACTATGTT


 


TGTACCTGGCAGGATATTCACAGAAATAAAATATTTATTGGCCATCTACT


 


TTGTTTAAGACCTCTTAACAAACCATAACTTATTAAAGCATAAAGTAACA


 


TACATAGTAAATACTTTTAAAATCTGTAAACAACTAATTCCTTTCTTCTT


 


GTGAAGTCTTGTTTAGATCATTAAAGTAATAGCAGATTTTCTCACAACAG


 


GTTTGTGAATATTGTCTGTTTAACATGAAAACTATAAAAAAATTAAAGAC


 


AATTGATATATATTTATTCAACTATGTCAACTCAAAGATGATCTGCAATT


 


GTTTTCTGAATAACTTATTAATAATGCTTAGGCCCCTTTGTTGAACATGC


 


TTTTATTTGTGTAAATAAGAATTCATTTAAAAATACATTGTACAACTTCA


 


ACACATTGTGTGTCCCTGAAGGTACTCTGAGATTTTGCAGTTATAGTATA


 


AATGAGACAAAACGGCAGAGAAAATATTCCCCATGTGTAATTCTTTCTAC


 


ATTTATTTCCCACATCAATCTCACAAGTGTTTTTATTTCACACTGATTGA


 


TATCATTGAGCACATACCTCAATATCTATTATCACAAAAACTATCATTAT


 


CAACAAGGACTTTAAAAAATATCTAAACATTATTATCTGGGTAGCAACTC


 


TATACTCCATTTTATCCATTAATTTTGTCTAATTAGTAAAGAAGTACTTA


 


TGGTAAAAACAAATTAAAAATAGTACAGAAAACATACTCCTGTATGCAAT


 


TATTACAAATATTTTATTTAGTTCCTATAAAGTATTTACATAGCTGAGAT


 


CACTATATAATATTATACTCATGTTACTTTATGTCCTAACTTTATATCA


 


Human Genome Map 11q23.2-q24.2 (2040 bp sequence)


(SEQ ID No. 83)


51A


CGGCTCTCCTGGCCTCGCGCTGCACATTCTCTCCTGGCGGCGGCGCCACC


 


TGCAGTAGCGTTCGCCCGAACATGGCGACACGGAGCAGCAGGAGGGAGTC


 


GCGACTCCCGTTCCTATTCACCCTGGTCGCACTGCTGCCGCCCGGAGCTC


 


TCTGCGAAGTCTGGACGCAGAGGCTGCACGGCGGCAGCGCGCCCTTGCCC


 


CAGGACCGGGGCTTCCTCGTGGTGCAGGGCGACCCGCGCGAGCTGCGGCT


 


GTGGGCGCGCGGGGATGCCAGGGGGGCGAGCCGCGCGGACGAGAAGCCGC


 


TCCGGAGGAAACGGAGCGCTGCCCTGCAGCCCGAGCCCATCAAGGTGTAC


 


GGACAGGTGAGCAGTTTTGCAACCCGCCTCCCTCCAGTTTTTTCCTCTCC


 


CTGCACTTCCTCACCCCCGCATCCATCCGTTGCAGTCGCCTCCTAGGTGC


 


AGGCACCACTGGGGACTTCCCGGCTTGCATTTGTTTTTTTCCTTCACGAG


 


TACAACCGTCAGCACTTGAATCGCATTGATCTTTCCTTCTTCCTGTCGAT


 


TTAGTAAACGTATTCCAGGTAACTCGCCGGGTGCAGTGCGTATTACCCCA


 


GGGTGTGTGCAGAGAGATGTAGTTTCCGGCAGGTATAGGAGGGGTGCAGC


 


TTCATTTTACATCTGGATAAAAAACGGGCTTTCTTTAGTGTATCATCAGT


 


TGGCAGTGGAGGCGAGCACCCTGCAGTTGCGGTACACTTACACAGAACAG


 


CACGAGGTGGGGGTTTCCACACTTAGCATTATTAGCACAATAAAAGTGGG


 


CAAACCTGAAAGCTTGTCGACTATCTCTGTACAGTCAGACAAGAGGTGTG


 


TGTATGTGTGTGCGTGTGTAAAGGCTGAATTTTTAATTTTTAATTTTTGG


 


CGAGCGTGTGAGATGCTCTCCATTCCTTCTTCCCCACCCTTCAAGATGCT


 


GACTCTCCCACCCCCGTCAAGATAACTTTATTTTGGAGAGGAATACCCCT


 


CATGGCACTTGGAGATTTGAAAGGACTGCAGGAAATTTGGTGGGCATTAT


 


TATTCTATAAGTGATTTATTTCTACCCAGGCAATAGGTTTATTAGATCAT


 


AAGTAACGTGAATTTCACTTTTATGGTCAGACTTACTGCGAGGAATTGCA


 


GATGGAGTTTGTAGGTTAGGATCAGCACTGGCAAAATTAATTTGACCGTG


 


TTATTGCCTCATGAGACTCCCAGTCCTGCAGTTAAGATTGACATCAGCAA


 


AAGTATAAGGTCGGTGGGGGAGAAAAAGTAGGACCAGAGGAGGGGGTAAA


 


TACACTTGTTTTCTAGAGTCAAATTGTTCCTTTTGAAGTAGAAATTATTA


 


ATAAAAGATTACCCTGAGTTCTGCCTTTTCTCACTAATTTCACTTTAGCC


 


ATTTCTTCAGGAAATACAGAGTTAAATGTTCAACCCTTGGATCCAGGACG


 


AACCTTGTAAACATATCACCCTATTGTGTCATTTTGTTGGTGAAGAAACT


 


GAAGCGTGGAATGGTGAAGTGACTAGTCCAAGGTCATACCGGGAAGGTGG


 


CCTGCTCTCTAGTTTTTGTCTGCATTGTCTCAGTGACCTTTGCTTGACTG


 


CAGTCACCCTGTCTTTATGCAATGCTGCTGAAATACCTCCTTTCTAAAAT


 


AAAATAGATCTGGTATAAAGGGGGAAAGGATGGTGGTGACTGGGTGGGAG


 


CGTTGGATTTCCCTCCACTATTGGTCCCTGGGCAAGAATGTGTGCCCCAG


 


GGCATGTAACTAATGGTGGCCACAGGCTGCAGGAACCTGCATGCTCAGTT


 


CCTCTTGGGCCCAGATCCTTGTCCCCCTGTCCCCACCCCATATGACAAAT


 


ATGTGTATGAACAAAAAGAAGTCATCAAGGTCCTTGCTCTTAACAGCGAC


 


ACCAGCATGGGGCTGATGGAGGGTGGGAGAAGGAGGAGGAGTGGCCCACT


 


TCTTCATTGGGCCTCCGCAGTCAGCCCAGCTCTGCTGTGCTCTTGAATCA


 


GCATTCTGGGAACTGGGAGTTGGGGGCTGGTGGGAGACAA


 


Human Genome Map 8p11.2 (2100 bp sequence)


(SEQ ID No. 84)


52A


ACAAAAGGCAAATTGGTGTCTCTGTCCTGGAGTCCTTACTCCTCATCTTG


 


TGCTTAGACATGAAATTACACATCTCCAGCCTTGGGATTCCAGGACTTAC


 


ACCAGTAGCATGCCTATGTTCTAAGGCCTTTGGCCTGGGACTGAGAATTA


 


CACCATCAGCTTTTCTGGTTCTAAGGCTTCTGGACCTGAACTGAGCCATG


 


CTACCAGTATTTCAGGATGTTCAGCTTGCAGATAGCCTGTCGCGGAACTT


 


CTCAGCCTCTAGAATCACATGAGTCAATTCCCCTAATAAATCTCCTTTTA


 


TCTATCTGAACATCTCTCTTCATCTCTCCATCCATCCACTCATGTGTCCA


 


TCCATCCATCCATCTATTGCTATCTATCTATCCATCCATGCATCCATCCA


 


TTCAACCATCCATCCACCCATCCATCCATCCCTGTGCCATCTATATCTAT


 


CTATCTATATATCTATCTATCCATGCATCCATCCATCCATCTATCCATCT


 


ATCCATCCATCACTATCTATCCATGCATCCACCCATCCACCCATCCATCC


 


ATCCATCCATCCATCCATCACTATCTATCCATCCATGCATGCATGCATCC


 


ATCCATCCATCCATCCATCCATCCATCCATCCATTTATCGCTATCTATCT


 


ATCCATCCATGTATCCATCCATCCATCTGTTCATCTATCACTGTCTATAT


 


ATCTATGTATCTATCTATCCATCCATCCATGCATCCATCCATGCATCCAT


 


GCATCCATCTATCACTATCCATCCATCCATCCATCCATCCATTCATCCAT


 


CTATCTGTCTTCTACCTACCTACCTATCTAACTCTCTGGAGAACTCTGAC


 


TAATAAACTAGCTTTAAAACATGTTATTCTCTCTCTGCAATGTCTATTGC


 


TTTATCTTCAGGAACATTCCACACATCCTGTAAGACTTCAGTTAAATTAT


 


CTCTCTGTTTCTTCTCCAATCATCCTCTGCCTTCCCTAGTCTCCTAACGT


 


ACTTTGTACATCTGTCACAAACCCCTCATCATATTTACTGTAATTTTTTT


 


CCTACAGATTTGGATAGGAATTGAGCCATTTTTTTAATTTCACTTTTATG


 


GTTGTTACAAATAAAAGAGCAAGCAGGCCCCTCACTGTAATTCACCTGTA


 


TTTGCATTTAACTTATTAACCAAGGCATACTATTTCAAATAATCTAATAT


 


AGTATTTCCTATTTAATAACCAAACATACAGAACAGTTCCAAGCACATGT


 


AACCATGTGATACATTTTCCTCTTTGAATAATAAATATATTTCTTATAAT


 


TAATATGTGATAAAATTGCAATATTTTTAATCTCCTACATCCTTCTCTTT


 


TAACAGGTTTCCTTATCAACTGGTTCCTATCTCACGGGGTTGTTGCAGAG


 


ATGAGGAAAAAAAGTATTCTATTGGTTCATGCATCTCAAAATAGGCAGAT


 


TCTTTTCTCTGCTTCTTCCTTCATTGGCTCAGGTGTGGAGTGCTTCTCCC


 


AATTATATGTGCCAGCCTTGGTATGTTCTCATTGCTGTACCACACTGCCT


 


GAGACATCCAAGACCACATCTTCCTTTGGGGGCACATTGGACCTTTGTCA


 


TTGGCACTGGCAGGGAAGCTTTTATTTCACCAGGTCTAAGGCAATTCTTC


 


CAAAAAAATCCCAAATAGTGAAAGAATTGATTTATTCTTCTAATATTTAA


 


GCAAATGTAAAAAAAAAGTTACATTAGTTATGTTTTTTTCAGATTTTGGA


 


TCAGTGAGACTTCATTAAAACACTTTGAGGTTATAAAGCAAGTAATTTTT


 


GTTTCCAGAAAAGTTAGTTTCCTTTGGCTGAAGGGACATCTCTATGCAGG


 


CCAGATCAAGACAAAAATAACTTTTAAGAAGGGAAATGAGGGAATGGAGT


 


TTGGAAAACATAAATCCCACAGCAAAGTACGTCACCAACAATAAGAGTCA


 


TCTCTTTCACAGAGGCCTTTCCTAGAAAAGCCCTGACAGACTAGGAGTCC


 


AATCTTCGGCTCCCATAGCACCCATGCCTGCTTCCACTCTGGAGCTTACT


 


ACTTTGCGTTGAAATTAATTTTTACATGTCTATGGCTTCTATTACAAA






However since the in silico search was based on the H1 PSE consensus and considering that it was used as query allowing only the first and the last bases to be different in the targets, it can reasonably supposed to have identified only those promoters whose, structure is very similar to that of H1 (for sequences used as query see materials and Methods section). This is further supported by the fact that out of H1 no other previously known Pol III Type III promoters were found in our PSE-based collection. Therefore this finding together with the observation of the large sequence divergence among the PSE consensus sequences of U6, 7SK and H1 suggests that the use of a degenerated PSE consensus as query (most likely derived from a bioinformatic analysis of several known Pol III Type III promoter consensus elements) would bring to light a considerably higher number of novel PSE-dependent transcription units in the human genome that would better clarify the likely impact of this effect at genome scale.
In order to further characterize in silico the novel transcription units we arbitrarily assumed as transcribed the sequence stretch starting from the 21st nucleotide downstream the predicted TATA box. In addition a 4×T repeat was considered as a Pol III transcription STOP signal although events of “read through” are possible and most likely affected by sequence context features [19, 20]. Although it has to be emphasized that the transcribed region of each element of this collection needs to be experimentally determined case by case (possibly in the context of its target gene of regulation), based on their in silico characterization we selected 33 novel transcripts to be subjected to additional analysis.
In order to test if a common secondary structure could be a hallmark of the novel molecules an in silico analysis of their secondary structure was performed by mfold algorithm [21]. Results showed that although hairpins with short stems (5-7 base pairs) were frequent no shared secondary structures were recurrent indicating that a peculiar molecular organization is not the common hallmark of this set of non-coding molecules. Interestingly, although their averaged free energy (δG) was extremely variable (−42.7±41.2) four transcripts (11A, 20A, 21A, and 29A) showed a δG value significantly lower than all the others (δG<−100). A statistical analysis of such δG differences was performed bringing to light a group of transcripts (11A, 20A, 21A and 29A) whose δG is significantly lower then expected (Student't TEST, 33 degrees of freedom, α significance level=0.1 corresponding to a P-value of 0.0001) thus keeping in line with their physiologically functional molecular organization (FIG. 8).
In order to assess if the pool of transcription units was prevalently constituted by repeats such as retroposons we analyzed all the transcripts by Repeat Masker algorithm [22] evidencing that: i) only 2 out of 34 (5.9%) are Short Interspersed Nucleotide Elements (SINEs) such as 21A and 29A that were marked as AluJb elements. ii) three of them (8.8%) are part of Long Interspersed Nucleotide Element (LINE) such as 24A, 37A, and 38A. iii) two (5.9%) contained a MIR (17A and 40A) and iiii) three contained different types of Long Terminal Repeats (30A, 32A and 44A) (Table 2).







TABLE 2







Sequence analysis by RepeatMasker Web Server (available at:


http://www.repeatmasker.org/cgi-bin/WEBRepeatMasker)












Seq.
Rep.




Seq Name
Length
Length
Position
Type





11A
—
—
—
—


12A
—
—
—
—


14A
—
—
—
—


17A
159
115
 1-115
Mir (MIR3)


19A
—
—
—
—


20A
—
—
—
—


21A
333
307
 18-324
SINEs (AluJB)


22A
—
—
—
—


23A
—
—
—
—


24A
406
406
 1-406
Line L1 (L1MC)


27A
—
—
—
—


29A
360
286
 74-359
SINEs (AluJB)


30A
158
135
 1-135
LTR/MALR (MLT1G3)


31A
—
—
—
—


32A
140
140
 1-140
LTR (LTR7)


33A
—
—
—
—


34A
—
—
—
—


35A
—
—
—
—


36A
—
—
—
—


37A
 50
 50
 1-49
LINE (L1M4)


38A
357
348
 1-348
LINE (L1M3)


39A
—
—
—
—


40A
484
220
253-472
MIR (MIR b)


41A
—
—
—
—


42A
—
—
—
—


43A
—
—
—
—


44A
218
 52
 66-117
LTR/MALR (MLT1M2)


45A
—
—
—
—


47A
—
—
—
—


48A
—
—
—
—


49A
—
—
—
—


50A
—
—
—
—


51A
—
—
—
—


52A
—
—
—
—









Placing results in the appropriate context (such as considering that Alus, LINEs and MIRs constitute about 15%, 30% and 1-5% of the human genome respectively) one should expect a higher frequency of repeats in this novel pool of sequences. In addition we observed that no more than three of the repeats-containing elements are ascribed to the same class of molecules. Altogether these observations evidence that the novel PSE-dependent transcripts are not associated to a specific class of repetitive sequences scattered throughout the human genome but instead they constitute a novel eterogeneous set of Type III promoter-driven elements.
When these non-coding sequences were used to challenge the human genome database (BLAST Analysis) results showed that 7 were internal to known or predicted protein-coding genes, 4 being in antisense and 3 in sense configuration. Interestingly, most of the novel sequence elements not mapping in coding regions shared a high sequence homology ( ̃80%) to a Pol II transcript/EST that maps in a different locus (Table 3). Such homologies reached much higher values (often about 90%) if only parts of the putative transcripts were considered. In fact, no ESTs entirely containing one of our transcription units were found so that if a sense/antisense-based regulation would occur it should be related to parts of the ncRNA sequences while the other part could have structural properties that facilitate this regulatory action (perhaps binding specific structural proteins). Based on these observations, a novel control mechanism of gene expression could be postulated where Pol III (or Pol III-like) elements act as trans-locus antisense of their homologous protein-coding RNAs. In this model the Pol III co-genes in antisense configuration with respect to one (or more) specific target gene could regulate its expression either by interfering with its mRNA maturation (if the homologous region is internal to an intron) or by inhibiting protein translation (if the homology is associated to an exon).















TABLE 3











BLAST







Genomic
Blast Human

Human


Tr. Unit
Tr. Length (nt)
Hum. Gen. Map
Contig
Genome
gi (gen. ident.)
ESTs
gi
e-value























11A
344
14q22.1
—
H1 RNA
—
—
—
—


12A
141
2p24.3
RP11-
—
51460874
DB275493
83216976
2.00E-12





98I18


14A
148
3p12
RP11-
—
21206095
—
—
—





206J21


17A
159
9q22-q31
RP11-
GPR51 (intron 3)
51467683
—
—
—





349P17
Sense


19A
148
3p12.3
RP11-
—
19774315
—
—
—





206J21


20A
547
14q22.1
R218E20
—
11611180
—
—
—


21A
333
8q24.1
RP1-
CENPF (Intron
22657510
AA737281
2767556
1.00E-31





316L14
7,14,18) Antisense


22A
235
6q16-q21
RP11-
—
10045412
AA361955
2014276
6.00E-29





487F5


23A
200
Xq21.3
RP13-
—
6855342
—
—
—





258015


24A
406
12q21
RP11-
—
9957971
DA811538
81279558
6.00E-15





997P16


27A
91
7q22
CTA-
—
2341013
—
—
—





369K23


29A
360
11p15
AJ400877
ASCL3 (intron 1)
8052236
BX645799
34480132
2.00E-36






Sense


30A
258
Xp11.4
RP11-
—
50582666
DA496935
80536970
3.00E-05





157D23


31A
231
12q21
RP11-
—
21039699
AW303617
6713306
2.00E-19





743I10


32A
140
17q21
MCK41
—
75875068
CA310957
24529055
9.00E-73


33A
210
1q32.2
RP11-
—
21622744
—
—
—





465N4


34A
33
5q15
RP11-
—
21281496
—
—
—





274E7


35A
351
8p11.2
RP11-
—
28565756
BF995135
12401458
5.00E-21





1147M13


36A
122
3p12
RP11-564-
—
20334518
—
—
—





P9


37A
49
14q13
RP11-
—
37550867
BM724961
19046292
4.00E-10





192K2


38A
357
4p15.31
RP11-
KCNIP4 (intron 1)
19807889
BF475563
11546390
8.00E-17





19D21
Antisense


39A
76
Xp11.3
RP5-
FLJ22843 (intron 10)
9581533
—
—
—





1158H2
Antisense


40A
484
11p15
RP11-
—
27413210
BG570298
13577951
4.00E-04





265F24


41A
79
2q31
RP11-
—
15668089
—
—
—





12N7


42A
122
3p12.3
RP11-
—
20334518
—
—
—





564P9


43A
65
4q34.3
RP11-
—
18129587
—
—
—





43303


44A
218
4q13.3
RP11-
—
18464317
—
—
—





401E5


45A
78
4p14
RP11-1I10
APBB2 )intron 1)
18450176
—
—
—






Antisense


47A
48
2q22.1
RP11-
—
16950374
—
—
—





745P9


48A
405
11q24.2
RP11-
—
32188045
—
—
—





168K9


50A
156
21q21
AP001675
—
7768691
—
—
—


51A
273
11q23.2
RP11-
SORL1 (intron 1)
14517581
BG698692
13966211
8.00E-04





730K11
Sense


52A
142
8p11.2
RP11-
—
28565756
—
—
—





1147M13









21A as Co-Gene Experimental Model

To test our hypothesis we selected one of the novel transcription units (here referred to as 21A) that maps in 8q24.13. If aligned to the human genome it shows several homology hits among which the highest were associated to multiple intronic regions of Centromeric Protein F (CENP-F; 1q32-q41) (Acc. N° NM016343) [23] thus constituting its putative natural trans-chromosomal antisense (FIG. 1A, B, C). Although similarly to all the 7SL/Alu-derived elements 21A is expected to be primate specific [24] an evolutionary conservation analysis was performed aligning its sequence with the mouse predicted CENP-F gene. No significant similarities were found indicating that in rodents a putative CENP-F antisense regulatory role, if any, would be associated to a different class of noncoding elements. Interestingly, in spite of its high sequence similarity with other human Alus, 21A lacks the Alu-specific intragenic consensus elements needed to promote its Pol III transcription such as the blocks A and B [25]. This was a further clue pointing toward a 21A transcription driven by an extragenic Type III promoter.
To check for 21A expression in cultured cells, we performed Northern blot analysis on total HeLa cell RNA using a 21A dsDNA probe. Two positive bands were detected: one corresponding in size to the expected 21A transcript (−300 nt), and the other one corresponding to a high molecular mass transcript (as expected for CENP-F mRNA) (FIG. 2A). However, considering that the 21A double-strand cDNA probe would detect transcription of 21A-similar Alus from multiple loci we also amplified a 21A-specific cDNA from total RNA samples, extracted from skin fibroblasts and four tumor cell lines (293T, LAN5, HCT, HeLa), by random hexamer-based RT-PCR in order to better identify a 21A-specific transcription product (FIG. 2B). The DNA band obtained was then purified and sequenced evidencing that the amplification product was the expected 21A. In addition, to better assess 21A transcription we fused its promoter to a luciferase silencer hairpin and co-transfected this construct with a plasmid expressing luciferase. Results showed a halved luciferase activity 48 hours after transfection thus demonstrating an efficient transcription directed by 21A promoter. In the same experiment a set of five novel promoters from our collection were tested demonstrating an active transcription of the hairpin promoted by four of them (FIG. 2C). These data support the conclusion that the majority of the novel putative transcription units is under the control of active extragenic Type III promoters.
Pol III-Dependency of the Novel Transcription Units
The same experiment as above was repeated after 24 hours of cell treatment with ML-60218, a cell-permeable indazolo-sulfonamide compound that displays broad spectrum inhibitory activity against RNA Polymerase III [26]. Results showed an efficient luciferase-silencing activity in the absence of the Pol III inhibitor (as evidenced by a decreased luciferase emission) while after treatment with ML-60218 the luciferase signal was increased (FIG. 2D).
Altogether, these results evidence a decrease in hairpin synthesis of the novel transcription units as consequence of the reduced Pol III activity according with their Pol III-dependency of their transcription.
21A Acts as CENP-F Regulatory Co-Gene Modulating its Expression at Post-Transcriptional Level
To test whether the 21A transcript acts as an antisense inhibitor of CENP-F expression we measured by Western analysis CENP-F protein level in HeLa cells transiently transfected with four different 21A constructs carrying: i) the whole 21A region containing both DSE and PSE elements (p21A), ii) its upstream moiety, that contains the DSE and a MIR element (p21A-1), iii) the novel Pol III Type 3 transcription region (that includes an Alu Jb module) (p21A-2) and iiii) an empty vector as Mock control (pMock). Starting at 24 hours from transfection of the whole 21A region, inhibition of CENP-F accumulation (followed by a rapid degradation) was observed. Such inhibition was specifically associated to constructs expressing the 21A RNA (p21A, p21A-2) while the MIR element in the upstream moiety of the fragment (p21A-1 construct) was ineffective (FIG. 3 A-D). In this context it has to be noted that a slight delay of 21A-2 inhibitory action if compared to the immediate CENPF decrease determined by 21A has been observed suggesting that a more detailed mutation analysis of 21A promoter could bring to light further Type III promoters regulatory regions. In order to measure the occurrence of 21A transcription in transfected cells we analyzed by Real Time quantitative RT-PCR its RNA level in all the samples. As expected a very high amount of 21A transcript was detected in p21A and p21A-2-transfected cells (210 and 480-fold respectively at 48 hours from transfection) while the 21A RNA content of samples transfected with pMock control plasmid and/or with a construct containing the promoter lacking the transcribed region (p21A-1 construct) were essentially stable showing a very low basal level of 21A expression in untransfected HeLa cells (FIG. 3 E-H). All the PCR products were analyzed in their dissociation curve showing a single characteristic pick (at 78/79° C.) in p21A/p21A2-transfected samples significantly reduced in pMOCK/p21A-1. On the contrary the cells transfected with the two control plasmids (pMock/p21A-1) showed a dissociation pattern characteristic of an eterogeneous population of molecules (FIG. 30). Again these results confirmed an active synthesis of the exogenous 21A ncRNA transcript in p21A/p21A-2-transfected samples that was strongly reduced at a very low endogenous basal level in the samples lacking the transcript region (pMOCK/p21A-1). As a consequence of 21A very active transcription the level of CENP-F mRNA (as determined by Real-Time RT-PCR) was significantly decreased in p21A/p21A-2-transfected cells while no major CENPF mRNA variations were observed in pMOCK/p21A-1-transfected cells (FIG. 3A-D). Altogether these results evidenced an inverse correlation between 21A transcription and CENPF expression. Therefore, considering the high homology level between 21A transcript and three CENPF hnRNA intronic portions and in the light of the above results (obtained either at protein level as well as at RNA level) we suggest a mechanism of antisense inhibition of CENP-F mRNA maturation by the 21A transcript.

21A Overexpression Specifically Inhibits Cell Proliferation in Humans

Given the central role of CENP F in mitosis we tested the effect of ectopic 21A expression on cell proliferation. By measuring [3H]-thymidine incorporation we evidenced a dramatic arrest of cell proliferation after 48 hours in 21A-transfected cells. Again, the effect was specifically associated to the downstream 21A transcribed region (p21A/p21A-2 constructs) while transfection of the MIR-containing upstream moiety (p21A-1 construct) did not alter cell proliferation (FIG. 4A). Although at the present state we cannot exclude a contribution to this effect by Alus from other loci, this experiment evidence an inverse correlation of 21A transcription and cell proliferation that is in accord with the inhibition of CENPF synthesis here demonstrated.
To further support the antisense role of 21A we transfected Hela cells with a construct expressing the transcript in antisense configuration (here referred to as pAnti-21A) thus quenching the activity of the endogenous 21A molecules. Results showed an increased cell proliferation 24/48 hours after transfection. Similar results were obtained when a 21A-specific siRNA expressing construct was transfected in HeLa cells while the negative control sample (cells transfected with an unrelated chicken-specific siRNA) maintained a cell proliferation rate similar to that of pMock-transfected cells (FIG. 4B). In both the experiments an increased CENP-F synthesis was detected together with the concomitant 21A-RNA decrease in Anti/si21A-transfected cells, as evidenced by Real-Time RT PCR (FIG. 4 C,D). As shown in these experiments CENPF modulation and 21A RNA decrease were analyzed only at 0, 24, 48 hours after transfection rather then at 0, 24, 48 and 72 hours as in the previous experiments. In fact, the proliferation increase that follows to 21A downregulation brings in advance the cells at overconfluence so that the effect that we would measure on CENPF synthesis at 72 hours after transfection would be strongly biased by this technical limitation.
These data suggest that the decreased amount of 21A transcript consequent to its siRNA-mediated silencing, as well as its suppression by antisense technology specifically increase CENP-F synthesis thus keeping in line with the proposed role of 21A as CENP-F regulatory co-gene. In addition, it has to be considered that the increased proliferation rate here observed supports the idea of a widespread regulatory action of 21A that may control at post-transcriptional level the expression of several target genes similarly to what has been proposed for miRNAs [27].
The 21A Regulatory Effect is Human-Specific
Considering that a 21A-driven cell proliferation inhibition is expected to be primate specific (Alu sequences were not found in other mammalian orders) we tested for its eventual occurrence in mouse. In fact, this would keep in line with an unspecific effect of 21A on cell proliferation may be due to the activation of a more general biological process such as most likely the interferon response (an antiviral cell reaction shared by all mammals) rather then a specific multilocus 21A regulatory action. As expected results showed that after transfection of p21A, p21A-1, p21A-2 and pMock the murine fibroblast NIH 3T3 cells did not show any proliferation decrease as assessed by [3H]-thymidine incorporation (FIG. 5). Therefore the 21A specie-specificity of action together with its inability to cause an unspecific cell reaction that leads to a proliferative blockade in mice further strengthen a 21A-specific (perhaps multilocus) regulatory role.
21A is a Key Factor of Cell Proliferation Control
As demonstrated by transfection experiments 21A overexpression is inversely correlated to cell proliferation. According with this finding its expression is very low in fully proliferating HeLa cells. Therefore in order to further demonstrate the inverse correlation between the endogenous 21A expression and cell proliferation we analyzed by quantitative Real Time RT-PCR its transcription level in different cell types with various proliferation potential. Results showed that three immortalized/fully proliferating cell lines here analyzed (HeLa as cervical adenocarcinoma; 293T as renal epithelial adenovirus transformed cells; LAN5 as neuroblastoma) the level of 21A transcription was very low if compared to the unproliferating/resting PBL cells (such as peripheral blood lymphocytes) in which a 276-fold increased 21A transcription was evidenced. I the same experiment, according with an inverse correlation between endogenous 21A transcription and the cell proliferation rate, the 21A RNA level in primary skin fibroblasts (whose proliferation rate is significantly lower than that of the tumor cell lines here analyzed) showed a 23-fold increased if compared to 393T cells and a very low expression level if compared to the resting/unproliferating PBL (FIG. 6). Again the dissociation curve analysis of 21A amplification product showed in PBL a pick at 78-79° C. characteristic of a single specific molecular specie that resembled the one obtained in 21A/21A-2 transfected cells (where the amount of 21A transcripts was strongly increased) although a slight shoulder, most likely due to a cross-amplification of other very similar transcripts, revealed a detectable endogenous Alu transcription background (FIG. 6). Altogether these results evidence a very active 21A transcription in PBL/resting cells that furtherly strengthen the idea of 21A as a novel key factor of cell proliferation control.
In order to check if the endogenous 21A over expression in unproliferating cells was related to a widespread increased RNA polymerase III activity rather then a 21A-specific activation we measured by Real Time RT-PCR the 5s rRNA expression level in the same samples. The results showed no direct correlation between 5s rRNA expression and the cell proliferation rate variations evidencing that the 21A over expression in resting cells was the consequence of a 21A-specific transcription activation rather then a more wide, unspecific increase of Pol III activity (FIG. 6). Altogether these results suggest an unexpectedly specific expression regulation of 21A promoter (related to the cell proliferation state) that needs to be investigated in detail.
CONCLUSIONS
We here propose that the non-coding fraction of the human genome includes a larger than expected number of ncRNA genes controlled by DSE and PSE promoter elements. Due to their promoter structure, a number of these genes is likely to be transcribed by Pol III. We refer to them as co-genes since they could specifically co-act with a protein-coding Pol II gene. Given the very high sequence homology between Pol III and Pol II transcript pairs and in the light of the results we have obtained investigating the regulatory activity of 21A transcription unit, we propose that a large part of these novel elements may act as antisense inhibitors of protein translation and/or mRNA maturation although some of them (those whose homology with the Pol II target gene is in sense configuration) could play a role in gene expression regulation with different mechanisms. Altogether these findings provide evidence for the existence of a ncRNA gene set associated to PSE/DSE-containing promoters, whose products co-act with a corresponding set of protein-coding targets.
In conclusion, this study provides i) a collection of novel non-coding transcripts to be investigated for their potential regulatory action with respect to Pol II target genes ii) a novel source of PSE-dependent promoters useful for the identification of common regulatory regions specific for this type of promoters, iii) a novel class of molecules involved in the RNA gene expression regulatory mechanisms iiii) a novel transcript (21A) whose intriguing role in tumor cell proliferation control would need to be investigated in detail in the context of cancer studies.
REFERENCES


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## Claims

1. An isolated nucleic acid molecule that consists of a sequence selected from the group consisting of SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83 and SEQ ID NO: 84.

2. The isolated nucleic acid according to claim 1 that consists of a sequence selected from the group consisting of SEQ ID NO: 54, SEQ ID NO: 57, SEQ ID NO: 71, SEQ ID NO: 78 and SEQ ID NO: 83.

3. The isolated nucleic acid according to claim 1 that consists of the sequence of SEQ ID NO: 71.

4. The isolated nucleic acid according to claim 1 that consists of the sequence of SEQ ID NO: 54.

5. The isolated nucleic acid according to claim 1 that consists of the sequence of SEQ ID NO: 57.

6. An expression vector comprising the isolated nucleic acid of claim 1.

7. An array for the detection of specific nucleic acid sequences containing a repertoire of nucleic acids according to claim 1.

8. An isolated nucleic acid sequence that comprises a promoter sequence, and the isolated nucleic acid of claim 1.

9. A vector comprising the isolated nucleic acid according to claim 1, capable of expressing or silencing an RNA polymerase II transcribed specific nucleotide sequence.