FR2833969A1 - Biochip that carries high purity molecular probes, useful e.g. for diagnosis, specifically of breast cancer, and for analysis of DNA repair - Google Patents

Abstract

Biochip (A) having, on at least one support, at least one molecular probe (I) that is of high purity, is present in known amount and is identified from its nucleotide sequence, is new. Biochip (A) having, on at least one support, at least one molecular probe (I) that is of high purity, is present in known amount and is identified from its nucleotide sequence, is new. (I) is all or part of a DNA or cDNA characteristic of a specific gene. High purity indicates absence of chemical reagents, free oligonucleotides and fragments that do not correspond with the probe (fragments of the probe or primers); known quantity indicates that the amount used is exactly known because a known volume of known concentration is deposited; and the base sequence for at least enough of the gene for definition of gene specificity has been determined. Independent claims are also included for the following: (1) preparation of biochips of very high quality; and (2) biochips prepared by method (1).

Description

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 Process for preparing biochips, high quality control, the thematic biochips or screening thus prepared, and their applications.

TECHNICAL FIELD OF THE INVENTION The present invention relates to the technical sector of biochips (called biochips "or more recently microarrays"), that is to say, as known to those skilled in the art, supports for example of the type glass, glass-silica, plastics or Nylon TM membrane, or any other suitable support, as will be seen in the non-limiting examples given below, on which are fixed or deposited (spotted>>) gene fragments, cDNAs or cDNA fragments, or oligonucleotides.

It is also possible to fix or deposit the sample nucleic acids on surfaces with electronic pads, by using the electrostatic attraction of + and - charges, or supports coupled to semiconductors.

Glass is preferred as a carrier because it is inert, resistant to high temperatures, has low natural fluorescence, and is easy to use for depositing samples, but other supports can now be used, as shown below.

A frequent use of such biochips, among other uses, is to verify the presence of transcripts (mRNA) in a given biological medium, by looking for whether this hybrid medium or not with the DNA of a given chip.

Detection can be by conventional fluorescence or radioisotope methods, or any other known detection method or that would be deemed appropriate by those skilled in the art, such as colorimetric and analog methods or semiconductors.

It is known that the genetic information of any living species is coded as a very long nucleotide base sequence, the DNA, composed of four nucleotides called G, C, T, and A. The DNA chain forms the well known double helix. Each strand of the helix is complementary to the other because the nucleotides are able to recognize their complementary nucleotide, which gives AT and GC bonds.

The principle of recognition by a biochip is to fix on a support a given selection of genes or gene fragments in the form of a single strand (capture probe). We then proceed to a

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 incubation in the presence of the medium to be determined, and, if the complementary sequence of genes (target DNA or target DNA) is present in said test medium, this sequence will specifically recognize on the biochip its complementary sequence and form a double strand of DNA. This process is called hybridization. It results from collisions between the various strands and progressive formation of the double helix as and when the recognition of the complementary.

Usually, the biochips consist of a support on which multiple selections of genes or gene fragments have been fixed or deposited, each being a priori specific for the hybridization with, and therefore the detection of, DNA sequences. DNA sought.

In the current state of the art, it is intended to detect in a single test the expression (or, more specifically, the transcripts) of many genome sequences.

DNA microarray technology therefore consists of the hybridization of DNA molecules on a solid support with a labeled probe. There are different types of media. The most commonly used are glass slides and nylon membranes.

There are two methods of manufacturing biochips.

The first consists of micro-deposits of DNA molecules (complementary DNA or oligonucleotides).

The second is developed by Affymetrix: this is the in situ synthesis of oligonucleotides.

Several applications of biochips DNA are possible. An interest is the study of the transcriptome. This makes it possible to simultaneously measure the expression of hundreds (or even thousands) of genes. Several scientific works have shown the interest of DNA microarrays and transcriptome analysis in medicine and in the general field of life sciences.

In terms of products, biochips are marketed (Clontech company, Incyte, Research Genetics, Affymetrix).

These so-called thematic biochips allow the study of a given biological process at the molecular level. For example, this may concern apoptosis (cell death), the cell cycle, the immune response. These biochips are of relatively low density (of the order of 200-300 genes / cm 2).

There are also so-called screening biochips. It is then high density biochips allowing the deposit of several thousand genes on a single support.

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Technical problem: The quality of known biochips is very controversial. In fact, following contamination problems that occurred during the technical preparation of the probes, the genes deposited on the supports do not always correspond to those supposed to be theoretically present. The interpretation of the results is then vitiated by many inaccuracies, even errors, which can only be corrected by the use of other alternative techniques of molecular biology (quantitative PCR, Northern blots, ...). There are also problems of sequences, positions on the blade. It is currently not known how to make high quality bipiles.

The diagnoses made using known biochips are either very imprecise or erroneous, which requires validating or reversing them by alternative techniques. The interest of the use of known biochips is therefore greatly reduced.

The production of high-quality biochips is therefore a real need because of the search for greater precision in biological diagnoses, and an increased need for thematic diagnoses that are finer in order to meet scientific and economic expectations. public health and all life sciences.

In addition, it would be very interesting to develop microchips precisely adapted to the study of a biological process in a given model.

It would also be of utmost importance, especially in oncology, to develop biochips that are accurate, reliable, and comprehensive diagnostic tools for the practitioner.

quelle que soit la finalité d'utilisation de ces biopuces, et que ces biopuces soient dites thématiques (ou à thème ) ou bien dites de criblage , ou représentent diverses combinaisons de telles biopuces sur un même support. The invention relates, for this purpose, biochips which will be designated here by the term of very high quality, which term will be defined below,

whatever the purpose of use of these biochips, and that these biochips are so-called thematic (or thematic) or so-called screening, or represent various combinations of such biochips on the same support.

The invention also relates to said biochips employed in, and adapted for, other technological fields, such as the medical, veterinary, phytosanitary and all similar fields of all life sciences (see applications section).

SUMMARY OF THE INVENTION: The present invention aims to manufacture biochips here called very high quality zu or high quality (cc controlled) for the molecular study of

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 specific diseases, particularly in the medical sector and more particularly oncology, including (but not limited to) breast cancer, capable of representing real diagnostic tools, but also, with the necessary adaptations, in life sciences including plant health.

Detailed description of the invention
BIOPUCES with high quality molecular probes
The invention relates first of all to new biochips of very high quality, capable of fulfilling biological diagnostic functions that have not been obtained to date, or with a much lower level of precision.

concept conduit à des avantages pratiques d'une très grande portée médicale (ou dans d'autres domaines mentionnés id dans la section applications))). It is an entirely new concept, and the merit of the invention is to have set itself the ambition of cutting-edge research in this very difficult scientific and technical sector, as will be seen below. This

concept leads to practical benefits of a very large medical scope (or in other areas mentioned id in the applications section))).

According to the invention, the biochips are characterized in that they comprise, on at least one support, at least one molecular probe which is: of high purity in known quantity deposited on said support; and identified in its nucleotide sequence.

sonde moléculaire : désigne la totalité ou un fragment d'ADN, ou d'ADNc, caractéristique d'un gène donné et répondant (dans le cadre de la présente invention) aux trois exigences qui viennent d'être précisées. The terms between are known to those skilled in the art, or understandable to those skilled in the art, but the following definition will be given, which will be valid throughout the present application, including the claims:

molecular probe: refers to all or a fragment of DNA, or cDNA, characteristic of a given gene and responding (in the context of the present invention) to the three requirements that have just been specified.

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 In the general framework known from the prior art and general knowledge of the skilled person, the definition is naturally identical, but the three requirements are not present or collected.

  high purity or very high purity means that the molecular probe is freed of all chemical reagents, free oligonucleotides, and nucleotide fragments that do not correspond to the probe (probe fragments and / or primers or primers); one operates as will be seen, and not limited to, by means of membranes or other equivalent technologies known to those skilled in the art.

 in known quantity means that one has access to the precise amount deposited because it results from a deposit on the support of a known volume of starting suspension, itself of known concentration.

  identified in its nucleotide sequence means more specifically identified in its informative nucleotide sequence with respect to the functions of the>> gene, which in turn means that the sequence of the nucleotide bases corresponding to any or part of a gene identified just before it is deposited.

 By all or part we will designate the minimum number of bases sufficient to define the specificity of a gene.

 We will still talk about the length of the sequence checked To further clarify these definitions essential to the clarity of the text, briefly recall a minimum of scientific data known to the skilled person.

A gene is composed of many fragments and represents coded genetic information.

Fragments consist of alternations of exons and introns.

The cell will remove all the intronic part (maturation of the gene in the cell) which reduces the fragment considered to a sequence of exons separated or connected together by junctions, the assembly forming the mature messenger RNA.

This RNA will serve as a template to be translated into proteins, which are the chemical molecules having a biological function in the cell.

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 since for example a number as high as a few thousand bases or as low as 50 bases.

To identify the specificity of a gene, scientists use well-known mathematical methods.

In general, it will take about twenty bases to ensure the specificity of the identified gene (ie to be certain that the succession of nucleotide bases is characteristic of the gene or unique in the genome of the organism studied) and allow identification, but in most cases scientists agree that identification is reliable only from a number of 50 to 70 bases. According to a particular and nonlimiting embodiment, the biochips according to the invention are very high quality biochips screening.

According to another particular and non-limiting embodiment, the biochips according to the invention are thematic biochips of very high quality.

According to a particular and non-limiting embodiment, the biochips according to the invention are characterized in that they comprise a combination of several thematic molecular probes.

According to another particular and nonlimiting embodiment, the biochips according to the invention are characterized in that they comprise a combination of at least one thematic molecular probe and at least one molecular screening probe.

 According to another particular, non-limiting embodiment of the invention, at least one of these probes is a molecular probe of very high quality.

 Preferably, all the molecular probes used are of very high quality.

Nonlimiting examples of such combinations include those described and claimed in the French patent application filed the same day on behalf of the Applicants, and entitled Thematic biochips and associated research modules.

The invention also relates to biochips of very high quality,

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 subject or not, either as such or as obtained by the implementation of the methods described below.

Thematic biochips: Unlike known themed biochips, which have a very large number of genes and can not form an accurate diagnostic tool (users are forced to correlate the 500 etc ... genes present with the results obtained, that is to say proceed by successive approximations and interpretations), the biochips according to the invention are characterized by a much smaller number of genes, themselves targeted on a specific pathology, for example breast cancer , and of very high quality or purity. Useful reference will be made in this field to the French patent application filed the same day on behalf of the Applicants, and entitled Thematic biochips and associated research modules.

These characteristics pave the way for the first time to real diagnostic tools, capable of allowing the doctor or the biologist both to characterize, to classify a tumor, and to evaluate its prognostic factors.

The invention therefore also relates to themed biochips as defined above - characterized in that they comprise a combination of special molecular probes adapted to include genes whose expression gives an indication on the tumor tissue (stage of the tumor, its aggressiveness, the cells affected, the invasiveness, the resistance or, on the contrary, the sensitivity to anti-tumor treatments ...).

The invention also relates to biochips which comprise only a combination of special molecular probes whose expression makes it possible to evaluate the resistance (or the sensitivity) of the tumor to such a treatment or to such a pharmacological molecule.

The invention also relates to such biochips, which further comprise molecular screening probes.

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The invention also relates to biochips comprising molecular probes of very high quality screening and also comprising a combination of special molecular probes adapted to include genes whose expression gives an indication of the tumor tissue (stage of the tumor, its aggressiveness , affected cells, invasiveness, resistance or, on the contrary, sensitivity to anti-tumor treatments ...).

The invention also relates to biochips characterized in that they comprise at least one screening biochip of normal quality, that is to say according to the prior art, in addition to one or more thematic biochips and / or very high screening. quality.

The invention also relates to biochips characterized in that they comprise at least one thematic biochip of normal quality, that is to say according to the prior art, in addition to one or more thematic biochips and / or screening of very high quality .

Most preferably, said biochips comprise in whole or at least in part high purity molecular probes prepared by one of the methods described below, and preferably entirely.

The invention also covers so-called "high-density" or so-called "high-density" biochips, characterized in that said biochips comprise all or at least part of molecular probes. high purity prepared by one of the processes described below, and preferably in whole.

The invention also relates to an original process for making thematic biochips or screening, of very high quality, controlled, as defined above, and this, whatever the specific applications of these biochips.

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In order to place the invention in context, a non-limiting example of a method according to the invention is characterized by a combination of 10 steps known per se, but never combined with each other or at least not entirely, or not in the manner in which the invention:
1. Extraction of plasmid DNAs.

2. Assay of plasmid DNAs;
3. Dilution of the plasmid DNAs.

4. Amplification of complementary DNAs (cDNA) or cDNA fragments, or fragments of DNA,
5. Purification of the obtained amplification products.

 6. Dosage of these products.

7. Dilution at the same concentration.

 8. Preparation of a plate where all the cDNAs are at the same amount.

 9. Sequencing of cDNAs.

 10. Deposit on the support (glass slide or other support).

 As will be seen below, the process according to the invention, making it possible to prepare very high quality molecular probes, for preparing thematic or screening biochips, or mixed as indicated above, is however characterized by three stages. essential, around which the skilled person will be able to build the overall process, with variants and options that will be within his reach, as the example of 10 steps that has just been given.

 We will recall the definitions of the steps considered.

Those skilled in the art will understand that the technical details given in the following definitions are merely illustrative, obviously non-limiting in scope
TECHNICAL PROCEDURE FOR THE PREPARATION OF MOLECULAR PROBES (COMPLEMENTARY HUMAN DNA OR DNA) AND
DEPOSIT ON GLASS BLADE This consists of deposits of DNA or complementary DNA on a glass slide or any other suitable support. These DNAs or cDNAs correspond to all or fragments of human genes of which they are characteristic.

The deposited DNAs are called molecular probes. These probes were, according to a non-limiting variant of the invention, obtained from bacterial clones marketed by IncyteTM (United States), at the end of various technical steps.

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 Invitrogen clones could have been used as well as clones that any laboratory would have to manufacture on its own.

1. Extraction of plasmid DNAs.

It is a circular DNA molecule of bacterial origin that contains the human complementary DNA. Once extracted, each plasmid DNA will serve as a template for the amplification reactions.

2. Plasmid DNA assay: It allows to estimate the amount of plasmid DNA obtained after extraction.

3. Dilution of plasmid DNAs: It allows to adjust all the DNAs at the same concentration.

4. Amplification of Complementary DNAs: The goal is to obtain the maximum of DNA molecules for deposits on a glass slide or any other suitable support. During this reaction, the DNA is placed in the presence of different reagents (salts, buffer, enzyme, etc.).

5. Purification: 96-well plates (Multiscreen PCR, Millipore) can be used which consist of a membrane that retains only the amplified DNA molecules. Excess reagents are removed. This step is essential in the process according to the invention because it makes it possible to obtain a solution of pure DNA. The quality of the DNA will depend on the quality of the fluorescent signal obtained during the study of the biochip.

Other formats, as understood by those skilled in the art, could have been used, such as 384-well plates or any other format.

Similarly, it would have been possible to use other purification methods, other than membrane, as it appears regularly and which are well known to those skilled in the art, such as gel filtration systems, column, chemical purification, ....

6. Assay: The yield of the amplification reactions is not identical for all the DNAs. It is therefore important to estimate the amount of DNA obtained.

7. Dilution: The results obtained with a biochip depend, in part, on the amount of DNA deposited on the slide. Now, to study a molecular mechanism, it is often necessary to study the level of expression of several genes at once, and to compare them with each other. So that this comparison is possible, the DNAs are diluted to the same concentration.

8. Preparation of a deposit plate: This is a step where the DNAs are in identical quantity (same concentration, same volume).

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9. Sequencing: It is essential for obtaining the very high quality of biochips according to the invention because it guarantees the identity of the gene studied and its position on the slide (see document previously sent).

où de haute pureté ou de très haute pureté' > signifie que la sonde r ctff moléculaire est débarrassée de tous les réactifs chimiques, des oligonucléotides libres, et des fragments nucléotidiques ne correspondant pas à la sonde (fragments de sonde et/ou amorces ou primers,)-, 1 où en quantité connue signifie que l'on a accès à la quantité précise déposée car elle résulte d'un dépôt sur le support d'un volume connu de suspension de départ, elle même de concentration connue ; et où identifiée dans sa séquence nuciéotidique"signifie de manière plus précise identifiée dans sa séquence nucléotidique informative par

rapport aux fonctions du gène", qui à son tour signifie que l'on a 1 procédé à l'identification de la séquence des bases nucléotidiques correspondant à tout ou partie d'un gène identifié, The general method according to the invention is of the type according to which at least one molecular probe formed of all or part of genes is deposited on a support, characterized in that it comprises at least one sequence of steps capable of forming - at least a molecular probe which is: of high purity in known quantity deposited on said support; - identified in its nucleotide sequence dz and capable of being deposited on a biochip support, and where molecular probe designates all or a fragment of DNA, or cDNA, characteristic of a given gene and responding (in the context of the present invention) to the three requirements which have just been specified.

where high purity or very high purity means that the molecular probe is free of all chemical reagents, free oligonucleotides, and nucleotide fragments not corresponding to the probe (probe fragments and / or primers or primers). ,) -, 1 where in known quantity means that one has access to the precise amount deposited because it results from a deposit on the support of a known volume of starting suspension, itself of known concentration; and where identified in its nucleotide sequence "more specifically means identified in its informative nucleotide sequence by

related to the functions of the gene ", which in turn means that the nucleotide base sequence corresponding to all or part of an identified gene has been identified,

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 where all or part here designates the minimum number of bases sufficient to define the specificity of a gene (or length of the sequence verified).

 The invention also relates to a process as described above, characterized in that it comprises in combination at least one assay, dilution and sequencing step.

 The invention also relates to a process as described above, characterized in that it comprises in combination at least one purification step, assay, dilution and sequencing.

 It will be understood that this is a general means whose very principle, and the function itself, have never been envisaged in the prior art.

Some nonlimiting examples of process definition obeying this general principle will be given below, and making it possible to implement the general function described.

According to a particular embodiment, the method according to the invention is characterized in that it comprises at least steps 6 (assay), 7 (dilution) and 9 (sequencing).

In particular, the assay step 6 is meaningless if it is not followed by the dilution step 7.

The invention therefore relates to a process for manufacturing thematic or non-thematic biochips of very high quality - of the type comprising at least some of the steps defined above, characterized in that it comprises at least steps 6 (dosage), 7 (dilution) and 9 (sequencing).

While not absolutely essential, as it may not be employed in certain applications or desired level of quality, the purification step is also important.

The invention therefore also relates to a method for manufacturing biochips of the type comprising the steps defined above,

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characterized in that it comprises at least the purification steps,
6 assay, 7 (dilution) and 9 (sequencing) combined.

 As a support, glass is clearly preferred, but it is also possible to use supports, for example glass, glass-silica, polymers and plastics, or NylonTM membrane, or any other suitable support, as will be seen in the non-conventional examples. limiting agents given below, on which are fixed or spotted (>)) gene fragments, cDNAs or cDNA fragments, or oligonucleotides.

 It is also possible to fix or deposit the sample nucleic acids on surfaces with electronic pads, by using the electrostatic attraction of + and - charges, or supports coupled to semiconductors.

 The fasteners or deposits may be made, especially in case of combinations, on one or possibly more supports, identical or different, which the skilled person can determine.

Principles + Manufacture of biochips of controlled quality.

 This production consists of a complementary DNA deposit on a glass slide or other support. We are talking about cDNA probes. These probes are obtained (by way of non-limiting example) from bacterial clones marketed by Incyte at the end of various technical steps. These are automated thanks to a robotic platform. An amplification robot (Amp4200TM Robot, MWG Biotech TM), a slide depot (Affymetrix 417tu Arrayer) and an Affymetrix 41 8 Scanner scanner were used.

 As indicated above, other equivalents or substantially equivalent equipment could have been used, and are known to those skilled in the art).

The preparation of the probes is (by way of non-limiting example) in 96-well plates and proceeds as follows:
1 Extraction of plasmid DNAs.

2 Assay of plasmid DNAs;
3 Dilution of plasmid DNAs.

4 amplification of complementary DNA (cDNA) or cDNA fragments, or DNA fragments,
Purification of the amplification products obtained.

 6 Dosage of these products.

 7 Dilution at the same concentration.

 8 Preparation of a plate where all the cDNAs are at the same amount.

 9 Sequencing cDNAs.

 1 0 Deposit on the glass slide or other support ..

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Each of the technical steps mentioned here is known per se. One of the original features of the invention is to have them combined to obtain cDNAs of optimal quality. Thus, the identity of the cDNAs deposited on the slide corresponds strictly to the theoretical list of the genes studied.

DATABASE The invention also relates to a database and its use which ensures the traceability of all the technical steps of gene preparation (technical parameters, batch numbers of reagents used ...). The results obtained during the various technical steps are included in this database.

More particularly, the invention relates to the method as described above, characterized in that the implementation of at least one of its stages, preferably several, and preferably all, is recorded and listed, including the results of the relevant step (s) in a database.

The invention also relates to the method as described above, characterized in that said database contains all or part of the code fragments used for the manufacture of biochips.

+ thematic biochips: From a bibliographic study and a synthesis work, we selected series of genes. The relevance of these biochips lies in the fact that the combination of genes chosen allows the study of a biological process in a given model. From a molecular point of view, the study of these genes makes it possible to answer a precise scientific question.

Four sets of genes or gene fragments have been developed, at the current stage that form a breast cancer biochip element, a biochip element DNA damage repair, a biochip element chemosensitivity, and a gene biochip element. hereditary predisposition to breast cancer ".

 The breast cancer biochip This biochip allows a classification of mammary tumors in order to improve the diagnosis, thus the prognosis and the therapeutic choice. The expression profile will make it possible to study the biopathological properties of mammary tumors.

According to a most preferred embodiment of the invention, a list of molecular probes corresponding to a mammalian breast cancer thematic biochip has been indicated in Appendix 1 SEQ 1 (reference will be made in this field to the

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 aforementioned French patent application, filed on the same day as the present application).

The Biochip DNA Lesion Repair According to another entirely preferred embodiment of the invention, a list of molecular probes corresponding to a DNA repair thematic biochip has been indicated in Annex 2 SEQ. will refer in this field to the aforementioned French patent application, filed on the same day as the present application)
The Chemosensitivity Biochip Its purpose is to enable the practitioner to predict the sensitivity or, on the contrary, the resistance of a tumor to an anti-cancer drug or to a given type of therapeutic treatment in order to guide the protocols during the treatment of patients.

 (Reference in this field to the above-mentioned French patent application filed on the same day as the present application.

+ Advantages of the invention:
In medicine, especially oncology: - Breast cancer is a public health problem.

 - Biochips are of high quality.

 - The biochips according to the invention form simple and accurate diagnostic tools, so reliable: the number of genes of each biochip is not high. Each of the genes or the combination of only a few genes has been chosen for the analysis of the results to provide precise answers.

 For example, if genes A and B are overexpressed then the tumor will be resistant to Taxol TM (anticancer drug).

 - Given the low density of biochips, we can consider the production of biochips at reduced cost.

Useful reference will be made in this field to the French patent application filed the same day on behalf of the Applicants, and entitled Thematic biochips and associated research modules.

The same types of advantages will be found in the other fields of application of the invention, which will be obvious to those skilled in the art, and examples of which are given below.

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The invention also relates to the various applications of biochips, and methods according to the invention as a means of accurate and reliable diagnosis, in all life sciences, including the medical, veterinary, phytosanitary.

The invention also relates to the various applications of biochips, combinations of molecular probes mentioned above and methods according to the invention, to any known genome study, for example a bovine, plant or bacterial genome; to verify the functionality of a gene in genetically modified organisms; and in virology, the biochips being then used to characterize the presence and the type of virus infecting an organism; and for the evaluation of the mechanisms involved and the quality of repair of DNA lesions, and in particular in oncology, in particular for breast cancer; and as a means of diagnosis in the field of all life sciences, and in particular in the medical or veterinary field in the phytosanitary field. biochips and methods according to the invention as diagnostic means.

Those skilled in the art will understand that biochips and combinations of molecular probes and the method according to the invention are applicable to the study of all the major cellular functions, in particular apoptosis, cell cycle, signal transduction, cell proliferation, proteolysis, mobility and cellular invasiveness, etc .... and all types of diseases, including inflammatory, infectious, endocrine, autoimmune, hereditary, nutritional, degenerative, chronic or acute, etc ...

The skilled person will understand without difficulty these applications, possibly make the necessary adaptations of routine, and consider other applications.

The invention will be better understood on reading the description which follows, and non-limiting examples below.

EXAMPLES Examples of Microarrays Prepared by the Method According to the Invention: Thematic biochip of breast cancer which comprises the characteristic molecular probes gathered in Appendix 1 SEQ 1. the skilled person will notice the limited number of probes (330) which allows a large number of probes. diagnostic accuracy.

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A biochip DNA lesion repair module has also been prepared by the method according to the invention, and comprises the characteristic molecular probes gathered in Annex 2 SEQ 2. the very small number of probes will also be noted.

The invention also covers all the embodiments and all the applications which will be directly accessible to the person skilled in the art upon reading the present application, of his own knowledge, and possibly of simple routine tests.

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<Tb>
<tb> ANNEX <SEP> 1 <SEP> SEQ <SEP> 1
<Tb>
THEMATIC BIOPUCE: MAMMARY CANCER, 333 MOLECULAR PROBES

<Tb>
<tb> Name <SEP> of <SEP> gene <SEP> Unigene
<tb> 5T4 <SEP> oncofetal <SEP> trophob1ast <SEP> g1ycoprotein <SEP> Hs. <SEP> 82128
<tb> acid <SEP> phosphatase <SEP> 5, <SEP> t <SEP> artrate <SEP> resistant <SEP> Hs. <SEP> 1211
<tb> actin, <SEP> alpha <SEP> 2, <SEP> smooth <SEP> muscle, <SEP> aorta <SEP> Hs. <SEP> 195851
<tb> activating <SEP> transcription <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 460
<tb> adrenergic, <SEP> beta, <SEP> receptor <SEP> kinase <SEP> 1 <SEP> Hs.83636
<tb> alcohol <SEP> dehydrogenase <SEP> 2 <SEP> (class <SEP> I), <SEP> beta <SEP> polypeptide <SEP> Hs.4
<tb> aldehyde <SEP> dehydrogenase <SEP> 1, <SEP> soluble <SEP> Hs.76392
<tb> alpha-2-macroglobulin <SEP> Hs. <SEP> 74561
<tb> androgen <SEP> receptor <SEP> (dihydrotestosterone <SEP> receptor <SEP>;<SEP> testicular <SEP> feminization <SEP>;<SEP> spinal <SEP> and <SEP> bulbar
<tb> muscular <SEP> atrophy <SEP>;<SEP> Kennedy <SEP> disease) <SEP> Hs. <SEP> 99915
<tb> annexin <SEP> A1 <SEP> Hs. <SEP> 78225
<tb> annexin <SEP> A8 <SEP> Hs. <SEP> 87268
<Tb>

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<Tb>
<tb> antigen <SEP> identified <SEP> by <SEP> monoclonal <SEP> antibody <SEP> Ki-67 <SEP> Hs. <SEP> 80976
<tb> apolipoprotein <SEP> AI <SEP> Hs. <SEP> 93194
<tb> apolipoprotein <SEP> D <SEP> Hs. <SEP> 75736
<tb> apoptosis <SEP> inhibitor <SEP> 4 <SEP> (survivin) <SEP> Hs.1578
<tb> aquaporin <SEP> 1 <SEP> (channel-forming <SEP> integral <SEP> protein, <SEP> 28kD) <SEP> Hs.74602
<tb> aquaporin <SEP> 7 <SEP> Hs. <SEP> 25475
<tb> armadillo <SEP> repeat <SEP> gene <SEP> deletes <SEP> in <SEP> velocardiofacial <SEP> syndrome <SEP> Hs. <SEP> 171900
<tb> ARP1 <SEP> (actin-related <SEP> protein <SEP> 1, <SEP> yeast) <SEP> homolog <SEP> A <SEP> (centractin <SEP> alpha) <SEP> Hs. <SEP> 2477
<tb> ATP-binding <SEP> cassette, <SEP> sub-family <SEP> C <SEP> (CFTR / MRP), <SEP> member <SEP> 5 <SEP> Hs. <SEP> 108660
<tb> basonuclin <SEP> Hs. <SEP> 64025
<tb> B-ce11 <SEP> CLL / 1vmphoma <SEP> 2 <SEP> Hs. <SEP> 79241
<tb> bc12 <SEP> assocaited <SEP> athanogenic <SEP> Hs. <SEP> 41714
<tb> bc12 <SEP> associated <SEP><SEP> protein <SEP> Hs. <SEP> 159428
<tb> beta-2-microglobulin <SEP> Hs. <SEP> 75415
<tb> Brcal <SEP> associated <SEP> RING <SEP> domain <SEP> 1 <SEP> Hs. <SEP> 54089
<tb> breast <SEP> and <SEP> bladder <SEP> overexpressed <SEP> gene <SEP> 1 <SEP> Hs. <SEP> 78768
<tb> Breast <SEP> cancer <SEP> 1, <SEP> early <SEP> onset <SEP> Hs. <SEP> 194143
<tb> breast <SEP> cancer <SEP> antiestrogen <SEP> resistance <SEP> 1 <SEP> Hs.273219
<tb> breast <SEP> cancer <SEP> antiestrogen <SEP> resistance <SEP> 3 <SEP> Hs.6564
<tb> breast <SEP> cancer <SEP> specic <SEP> gene <SEP> 1 <SEP> or <SEP> synculein <SEP> gamma <SEP> Hs. <SEP> 63236
<Tb>

<Desc / Clms Page number 20>

<Tb>
<tb> budding <SEP> uninhibited <SEP> by <SEP> benzimidazoles <SEP> 1 <SEP> (yeast <SEP> homolog), <SEP> beta <SEP> Hs. <SEP> 36708
<tb> bullous <SEP> pemphigoid <SEP> antigen <SEP> 1 <SEP> (230 / 240kD) <SEP> Hs. <SEP> 620
<tb> butyrate <SEP> response <SEP> factor <SEP> 1 <SEP> (EGF-response <SEP> factor <SEP> 1) <SEP> Hs. <SEP> 85155
<tb> bystin-like <SEP> Hs. <SEP> 106880
<tb> cadherin <SEP> 1 <SEP>;<SEP> E-cadherin <SEP> Hs. <SEP> 194657
<tb> cadherin <SEP>13;<SEP> H-cadherin <SEP> Hs.63894
<tb> cadherin <SEP> 15 <SEP>;<SEP> M-cadherin <SEP> Hs.148090
<tb> cadherin <SEP> 3, <SEP> P-cadherin <SEP> (placental) <SEP> Hs. <SEP> 2877
<tb> carboxypeptidase <SEP> B1 <SEP> Hs. <SEP> 180884
<tb> carcinoembryonic <SEP> antigen <SEP> Hs. <SEP> 220529
<tb> cartilage <SEP> oligomeric <SEP> matrix <SEP> protein (pseudoachondroplasia, <SEP> epiphyseal <SEP> dysplasia <SEP> 1, <SEP> multiple) <SEP> Hs.1584
<tb> catenin, <SEP> delta <SEP> 1 <SEP> Hs.166011
<tb> cathepsin <SEP> C <SEP> Hs.10029
<tb> cathepsin <SEP> D <SEP> (lysosomal <SEP> aspartyl <SEP> protease) <SEP> Hs. <SEP> 79572
<tb> cathepsin <SEP> Z <SEP> Hs.71388
<tb> caveolin-1 <SEP> Hs.323469
<tb> CD2 <SEP> antigen <SEP> (p50), <SEP> sheep <SEP> red <SEP> blood <SEP> cell <SEP> receptor <SEP> Hs. <SEP> 89476
<tb> CD34 <SEP> antigen <SEP> Hs. <SEP> 85289
<tb> CD36 <SEP> antigen <SEP> (collagen <SEP> type <SEP> I <SEP> receptor, <SEP> thrombospondin <SEP> receptor) <SEP> Hs.75613
<tb> CD3D <SEP> antigen, <SEP> delta <SEP> polypeptide <SEP> (TiT3 <SEP> complex) <SEP> Hs.95327
<Tb>

<Desc / Clms Page number 21>

<Tb>
<tb> CD3G <SEP> antigen, <SEP> gamma <SEP> polypeptide <SEP> (TiT3 <SEP> complex) <SEP> Hs.2259
<tb> CD68 <SEP> antigen <SEP> Hs.240615
<tb> CDC28 <SEP> protein <SEP> kinase <SEP> 2 <SEP> Hs.83758
<tb> CDC6 <SEP> (cell <SEP> division <SEP> cycle <SEP> 6, <SE> S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs. <SEP> 69563
<tb> CDC7 <SEP> (cell <SEP> division <SEP> cycle <SEP> 7, <SE> S. <SEP> cerevisiae, <SEP> homo1o <SEP> -1ike <SEP> 1 <SEP> Hs. <SEP> 28853
<tb> cell <SEP> division <SEP> cycle <SEP> 20, <SE> S. <SEP> cerevisiae <SEP> homolog <SEP> Hs. <SEP> 82906
<tb> cell <SEP> division <SEP> cycle <SEP> 25C <SEP> Hs.656
<tb> cellular <SEP> retinoic <SEP> acid-binding <SEQ> protein <SEP> 2 <SEP> Hs.183650
<tb> centromere <SEP> protein <SEP> E <SEP> (312kD) <SEP> Hs. <SEP> 75573
<tb> centromere <SEP> protein <SEP> F <SEP> (350 / 400kD, <SEP> mitosin) <SEP> Hs. <SEP> 77204
<tb> chitinase <SEP> I <SEP> Hs. <SEP> 91093
<tb> chitinase <SEP> 3-like <SEP> 1 <SEP> (cartilage <SEP> glycoprotein-39) <SEP> Us. <SEP> 75184
<tb> CHKI <SEP> (checkpoint, <SE> S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 20295
<tb> chromobox <SEP> homolog <SEP> 3 <SEP> (drosophila <SEP> HP1 <SEP> gamma) <SEP> Hs.8123
<tb> collagen, <SEP> type <SEP> I, <SEP> alpha <SEP> 1 <SEP> Hs.172928
<tb> collagen, <SEP> type <SEP> III, <SEP> alpha <SEP> 1 <SEP> (Ehlers-Danlos <SEP> syndrome <SEP> type <SEP> IV, <SEP> dominant) <SEP> Hs.119571
<tb> collagen, <SEP> type <SEP> VI, <SEP> alpha <SEP> 1 <SEP> Hs.108885
<tb> colony <SEP> stimulating <SEP> factor <SEP> 1 <SEP> (macrophage) <SEP> Hs. <SEP> 173894
<tb> CREB <SEP> binding <SEP> protein <SEP> (Rubinstein-Taybi <SEP> syndrome) <SEP> Hs. <SEP> 23598
<tb> cul1in <SEP> 4A <SEP> Hs. <SEP> 183874
<Tb>

<Desc / Clms Page number 22>

<Tb>
<tb> cyclin <SEP> B1 <SEP> Hs.23960
<tb> Cyclin <SEP> D1 <SEP> Hs.82932
<tb> cyclin <SEP> E1 <SEP> Hs. <SEP> 9700
<tb> cyclin <SEP> G <SEP> 1 <SEP> Hs. <SEP> 79101
<tb> Cyclin-dependent <SEP> kinase <SEP> 4 <SEP> Hs. <SEP> 95577
<tb> cyclin-dependent <SEP> kinase <SEP> inhibitor <SEP> 1C <SEP> (p57, <SEP> Kip2) <SEP> Hs. <SEP> 106070
<tb> cystatin <SEP> E / M <SEP> Hs. <SEP> 83393
<tb> cysteine-rich <SEP> protein <SEP> 1 <SEP> (intestinal) <SEP> Hs. <SEP> 17409
<tb> cytochrome <SEP> c <SEP> oxidase <SEP> subunit <SEP> VIe <SEP> Hs. <SEP> 74649
<tb> Cytochrome <SEP> c <SEP> oxidase <SEP> subunit <SEP> VIIa <SEP> polypeptide <SEP> 2 <SEP> like <SEP> Hs. <SEP> 30888
<tb> D123 <SEP> gene <SEP> produet <SEP> Hs. <SEP> 82043
<tb> DEAD / H <SEP> (Asp-Glu-Ala-Asp / His) <SEP> box <SEP> polypeptide <SEP> 11 <SEP> (S. <SEP> cerevisiae <SEP> CHLI-like <SEP > heiicase) <SEP> Hs. <SEP> 27424
<tb> density <SEP> regulated protein <SEP> Hs.22393
<tb> desmin <SEP> Hs.171185
<tb> dihydrofolate <SEP> reductase <SEP> Hs. <SEP> 83765
<tb> diphtheria <SEP> toxin <SEP> receptor <SEP> (heparin-binding <SEP> epidermal <SEP> growth <SEP> factor-like <SEP> growth <SEP> factor) <SEP> Hs. <SEP> 799
<tb> discointer <SEP> domain <SEP> Receiver <SEP> family, <SEP> member <SEP> 1 <SEP> Hs. <SEP> 75562
<tb> DNA <SEP> (cytosine-5 -) - methyltransferase <SEP> 1 <SEP> Hs. <SEP> 77462
<tb> dynein, <SEP> axonemal, <SEP> light <SEP> intermediate <SEP> polypeptide <SEP> Hs.33846
<tb> E2F <SEP> transcription <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 1189
<Tb>

<Desc / Clms Page number 23>

<Tb>
<tb> E74- <SEP>! <SEP> ike <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 166096
<tb> early <SEP> development <SEP> regulator <SEP> 2 <SEP> (homolog <SEP> of <SEP> polyhomeotic <SEP> 2) <SEP> Hs. <SEP> 75878
<tb> endoglin <SEP> Hs. <SEP> 76753
<tb> endothelin <SEP> receptor <SEP> type <SEP> B <SEP> Hs.82002
<tb> enhancer <SEP> of <SEP> peel <SEP> (Drosophila) <SEP> homolog <SEP> 2 <SEP> Hs.77256
<tb> Epidermal <SEP> growth <SEP> factor <SEP> Hs. <SEP> 2230
<tb> epidermal <SEP> growth <SEP> factor <SEP> receptor <SEP> (avian <SEP> erythroblastic <SEP> leukemia <SEP> viral <SEP> (v-erb-b) <SEP> oncogene
<tb> homolog) <SEP> Hs. <SEP> 77432
<tb> estrogen <SEP> receptorl <SEP> 1 <SEP> (alpha) <SEP> Hs.1657
<tb> estrogen <SEP> receptor <SEP> beta <SEP> Hs.103504
<tb> Estrogen <SEP> receptor <SEP> binding <SEP><SEP> associated site, <SEP> antigen, <SEP> 9 <SEP> Hs. <SEP> 9222
<tb> eukaryotic <SEP> translation <SEP> elongation <SEP> factor <SEP> 1 <SEP> epsilon <SEP> 1 <SEP> Hs. <SEP> 172247
<tb> eukaryotic <SEP> translation <SEP> initiation <SEP> factor <SEP> 3, <SEP> subunit <SEP> 4 <SEP> (delta, <SEP> 44kD) <SEP> Hs. <SEP> 28081
<tb> exportin, <SEP> tRNA <SEP> (nuclear <SEP> export <SEP> receptor <SEP> for <SEP> tRNAs) <SEP> Hs. <SEP> 85951
<tb> fatty acid <SEP> acid <SEP> binding <SEP> protein <SEP> 4, <SEP> adipocyte <SEP> Hs. <SEP> 83213
<tb> fatty <SEP> acid <SEP> binding <SEP> protein <SEP> 7, <SEP> brain <SEP> Hs. <SEP> 26770
<tb> fibroblast <SEP> growth <SEP> factor <SEP> 8 <SEP> Hs. <SEP> 57710
<tb> fibroblast <SEP> growth <SEP> factor <SEP> receptor <SEP> 1 <SEP> (fms-related <SEP> tyrosine <SEP> kinase <SEP> 2, <SEP> PfeiSer <SEP> syndrome) <SEP> Hs. <SEP> 748
<tb> flap <SEP> structure-specific <SEP> endonuclease <SEP> I <SEP> Hs. <SEP> 4756
<tb> forkhead <SEP> (Drosophila) -like <SEP> 16Hs. <SEP> 239
<tb> four <SEP> and <SEP><SEP> half <SEP><SEP> domains <SEP> 1 <SEP> Hs. <SEP> 239069
<Tb>

<Desc / Clms Page number 24>

<Tb>
<tb> fragile <SEP> histidine <SEP> triad <SEP> gene <SEP> Hs. <SEP> 77252
<tb> fructose-bisphosphatase <SEP> 1 <SEP> Hs. <SEP> 574
<tb> gamma-glutamyl <SEP> hydrolase <SEP> (conjugase, <SEP> folylpolygammagiutamyl <SEP> hydrolase) <SEP> Hs. <SEP> 78619
<tb> gap <SEP> junction <SEP> protein <SEP> alpha <SEP> 1.43 <SEP> kD <SEP> or <SEP> connexin <SEP> 43 <SEP> Hs. <SEP> 74471
<tb> GATA-binding <SEP> protein <SEP> 3Hs. <SEP> 169946
<tb> glutamate <SEP> receptor, <SEQ> ionotropic, <SEP> N-methyl <SEP> D-aspartate <SEP> 2A <SEP> Hs. <SEP> 167464
<tb> glutamate <SEP> receptor, <SEQ> ionotropic, <SEP> N-methyl <SEP> D-aspartate <SEP> 2C <SEP> Hs. <SEP> 36451
<tb> glutathione <SEP> S <SEP> transferase <SEP> pi <SEP> Hs. <SEP> 226795
<tb> glycerol-3-phosphate <SEP> dehydrogenase <SEP> 1 <SEP> (soluble) <SEP> Hs.25478
<tb> granzyme <SEP> A <SEP> (granzyme <SEP> 1, <SEP> cytotoxic <SEP> T-lymphocyte-associated <SEP> serine <SEP> esterase <SEP> 3) <SEP> Hs. <SEP> 90708
<tb> hepatocyte <SEP> nuclear <SEP> factor <SEP> 3, <SEP> alpha <SEP> Hs. <SEP> 105440
<tb> hepsin <SEP> Hs. <SEP> 823
<tb> high <SEP> mobility <SEP> group <SEP> (nonhistone <SEP> chromosomal) <SEP> protein <SEP> isoforms <SEP> I <SEP> and <SEP> Y <SEP> Hs. <SEP> 139800
<tb> high-mobility <SEP> group <SEP> (nonhistone <SEP> chromosomal) <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 80684
<tb> HIV-1 <SEP> Rev <SEP> binding <SEP> protein <SEP> Hs. <SEP> 171545
<tb> Homo <SEP> sapiens <SEP> ataxia-telangiectasia <SEP> group <SEP> D-associated <SEP> protein <SEP> mRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 82237
<tb> Homo <SEP> sapiens <SEP> clone <SEP> 24703 <SEP> beta-tubulin <SEP> MRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 179661
<tb> Homo <SEP> sapiens <SEP> HPV16 <SEP> E1 <SEP> protein <SEP> binding <SEP> protein <SEP> mRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 6566
<tb> Human <SEP> BRCA2 <SEP> region, <SEP> mRNA <SEP> sequence <SEP> CG006
<tb> Human <SEP> breast <SEP> cancer, <SEP> estrogen <SEP> regulated <SEP> LIV-1 <SEP> protein <SEP> (LIV-1) <SEP> mRNA, <SEP> partial <SEP > cds <SEP> Hs. <SEP> 79136
<Tb>

<Desc / Clms Page number 25>

<Tb>
<tb> Human <SEP> cellular <SEP> oncogene <SEP> c-fos <SEP> Hs. <SEP> 25647
<tb> Human <SEP> Ig <SEP><SEP> chain <SEP> gene <SEP> Hs. <SEP> 76325
<tb> Human <SEP> Phosphatidylinositol <SEP> (4,5) <SEP> bisphosphate <SEP> 5-phosphatase <SEP> homolog <SEP> MARNA, <SEP> partial <SEP> cds <SEP> Hs. <SEP> 21492
<tb> Human <SEP> ubiquitin <SEP> carrier <SEP> protein <SEP> (E2-EPF) <SEP> mRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 174070
<tb> hyaluronan-mediated <SEP> motility <SEP> receptor <SEP> (RHAMM) <SEP> Hs. <SEP> 72550
<tb> hydroxyacyl-Coenzyme <SEP> A <SEP> dehydrogenase / 3-ketoacyl-Coenzyme <SEP> A <SEP> thiolase / enoyl-Coenzyme
<tb> A <SEP> hydase <SEP> (trifunctional <SEP> protein), <SEP> alpha <SEP> subunit <SEP> Hs. <SEP> 75860
<tb> immunoglobulin <SEP> gamma <SEP> 3 <SEP> (Gm <SEP> marker) <SEP> Hs. <SEP> 140
<tb> inhibitor <SEP> of <SEP> growth <SEP> 1 <SEP> Hs.46700
<tb> inhibitor <SEP> of <SEP> growth <SEP> 2
<tb> inositoll <SEP> polyphosphate-4-phosphatase, <SEP> type <SEP> II, <SEP> 105kD <SEP> Hs.153687
<tb> insulin-like <SEP> growth <SEP> factor <SEP> 1 <SEP> (somatomedin <SEP> C) <SEP> Hs.85112
<tb> insulin-like <SEP> growth <SEP> factor <SEP> 2 <SEP> (somatomedin <SEP> A) <SEP> Hs.241317
<tb> insulin-like <SEP> growth <SEP> factor <SEP> binding <SEP> protein <SEP> 2 <SEP> Hs.162
<tb> insulin-like <SEP> growth <SEP> factor <SEP> binding <SEP> protein <SEP> 5 <SEP> Hs. <SEP> 102122
<tb> insulin-like <SEP> growth <SEP> factor <SEP> receptor <SEP> 1 <SEP> Hs. <SEP> 239176
<tb> insulin-like <SEP> growth <SEP> factor <SEP> receptor <SEP> 2 <SEP> Hs. <SEP> 76473
<tb> integrin, <SEP> alpha <SEP> 3 <SEP> Hs. <SEP> 265829
<tb> integrin, <SEP> alpha <SEP> 7 <SEP> Hs. <SEP> 74369
<tb> integrin, <SEP> alpha <SEP> L <SEP> (antigen <SEP> CD <SEP> 11 <SEP> A <SEP> (pi <SEP> 80), <SEP> lymphocyte <SEP> function- associated <SEP> antigen <SEP> 1 <SEP>;<SEP> alpha
<tb> polypeptide) <SEP> Hs.174103
<tb> integrin, <SEP> beta <SEP> 2 <SEP> (antigen <SEP> CD18 <SEP> (p95), <SEP> lymphocyte <SEP> function-associated <SEP> antigen <SEP>1;<SEP> macrophage
<tb> Hs.83968
<tb> antigen <SEP> 1 <SEP> (mac-1) <SEP> beta <SEP> subunit
<Tb>

<Desc / Clms Page number 26>

<Tb>
<tb> integrin, <SEP> beta <SEP> 4 <SEP> Hs. <SEP> 85266
<tb> integrin, <SEP> beta <SEP> 8 <SEP> Hs. <SEP> 184908
<tb> intercellular <SEP> adhesion <SEP> molecule <SEP> 2 <SEP> Hs. <SEP> 83733
<tb> interferon <SEP> alpha <SEP> inducible <SEP> protein <SEP> 27 <SEP> Hs. <SEP> 278613
<tb> interferon-induced <SEP> protein <SEP> 17 <SEP> Hs. <SEP> 146360
<tb> interferon-induced, <SEP> hepatitis <SEP> C-associated <SEP> microtubular <SEP> aggregate <SEP> protein <SEP> (44kD) <SEP> Hs. <SEP> 82316
<tb> interleukin <SEP> 10 <SEP> receptor, <SEP> alpha <SEP> Hs. <SEP> 327
<tb> interleukin <SEP> 2 <SEP> receptor, <SEQ> beta <SEP> Hs.75596
<tb> interleukin <SEP> 3 <SEP> receptor, <SEQ> alpha <SEP> (low <SEP> affinity) <SEQ> Hs.172689
<tb> kallikrein <SEP> 10 <SEP> Hs. <SEP> 69423
<tb> kallikrein <SEP> 13 <SEP> Hs. <SEP> 165296
<tb> kallikrein <SEP> 3, <SEP> (prostate <SEP> specific <SEP> antigen) <SEP> Hs. <SEP> 171995
<tb> kallikrein <SEP> 6 <SEP> Hs. <SEP> 79361
<tb> kangai <SEP> 1 <SEP> Hs. <SEP> 323946
<tb> keratin <SEP> 17 <SEP> Hs. <SEP> 2785
<tb> keratin <SEP> 18 <SEP> Hs. <SEP> 65114
<tb> keratin <SEP> 19 <SEP> Hs. <SEP> 182265
<tb> keratin <SEP> 5 <SEP> (epidermolysis <SEP> bullosa <SEP> simplex, <SEP> Dowling-Meara / Kobner / Weber-Cockayne <SEP> types) <SEP> Hs. <SEP> 195850
<tb> keratin <SEP> 7 <SEP> Hs. <SEP> 23881
<tb> keratin <SEP> 8 <SEP> Hs. <SEP> 104624
<Tb>

<Desc / Clms Page number 27>

<Tb>
<tb> KIAA0008 <SEP> gene <SEP> product <SEP> Hs. <SEP> 77695
<tb> KIAA0042 <SEP> gene <SEP> product <SEP> Hs. <SEP> 3104
<tb> KIAA0074 <SEQ> protein <SEP> Hs.1192
<tb> KIAA0101 <SEP> gene <SEP> product <SEP> Hs.81892
<tb> KIAA0125 <SEP> gene <SEP> product <SEP> Hs. <SEP> 38365
<tb> KIAA0159 <SEP> gene <SEP> product <SEP> Hs. <SEP> 5719
<tb> KIAA0166 <SEP> gene <SEP> product <SEP> Hs.115778
<tb> KIAA0430 <SEP> gene <SEP> product <SEP> Hs.166163
<tb> KIAA0758 <SEP> protein <SEP> Hs. <SEP> 22039
<tb> KIAA0788 <SEP> protein <SEP> Hs. <SEP> 181043
<tb> Kiss-1 <SEP> Hs. <SEP> 95008
<tb> lactate <SEP> dehydrogenase <SEP> B <SEP> Hs. <SEP> 234489
<tb> ladinin <SEP> 1 <SEP> Hs. <SEP> 18141
<tb> lamin <SEP> B2 <SEP> Hs. <SEP> 76084
<tb> laminin, <SEP> alpha <SEP> 3 <SEP> (nicein <SEP> (150kD). <SEP> ka1inin <SEP> (165kD), <SEP> BM600 <SEP> (150kD), <SEP> epilegrin) <SEP> Hs. <SEP> 83450
<tb> laminin, <SEP> gamma <SEP> 2 <SEP> (nicein <SEP> (100kD), <SEP> ka1inin <SEP> (I05kD), <SEP> BM600 <SEP> (100kD), <SEP> Herlitzjunctional
<tb> epidermolysis <SEP> bullosa)) <SEP> Hs. <SEP> 54451
<tb> LIM <SEP> and <SEP> SH <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 334851
<tb> LIM <SEP> Binding <SEP> domain <SEP> 2 <SEP> Hs.4980
<tb> LIM <SEP> domain <SEP> only <SEP> 4
<tb> lipocalin <SEP> 1 <SEP> Hs.204238
<Tb>

<Desc / Clms Page number 28>

<Tb>
<tb> lipoprotein <SEP> lipase <SEP> Hs.180878
<tb> LPS-induced <SEQ> TNF-alpha <SEP> factor <SEP> Hs.76507
<tb> lumicanHs. <SEP> 79914
<tb> lymphocyte-specific <SEP> protein <SEP> tyrosine <SEP> kinase <SEP> Hs. <SEP> 1765
<tb> MAD2 <SEP> (mitotic <SEP> arrest <SEP> deficient, <SEP> yeast, <SEP> homolog) <SEP> -like <SEP> 1 <SEP> Hs. <SEP> 79078
<tb> major <SEP> histocompatibility <SEP> complex, <SEP> class <SEP> II, <SEP> DQ <SEP> beta <SEP> 1 <SEP> Hs. <SEP> 73931
<tb> mammaglobin <SEP> 1 <SEP> Hs. <SEP> 46452
<tb> mania <SEP> fringe <SEP> (Drosophila) <SEP> homo1og <SEP> Hs. <SEP> 31939
<tb> matrix <SEP> metalloproteinase <SEP> 11 <SEP> (stromelysin <SEP> 3) <SEP> Hs. <SEP> 155324
<tb> matrix <SEP> metalloproteinase <SEP> 13 <SEP> Hs. <SEP> 2936
<tb> matrix <SEP> metalloproteinase <SEP> 14 <SEP> (membrane-inserted) <SEP> Hs. <SEP> 2399
<tb> matrix <SEP> metalloproteinase <SEP> 17 <SEP> Hs.159581
<tb> matrix <SEP> metalloproteinase <SEP>9;<SEQ> gelatinase <SEP> B <SEP> Hs.151738
<tb> MAX-interacting <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 118630
<tb> Meis <SEP> (mouse) <SEP> peer <SEP> 3 <SEP> Hs. <SEP> 117313
<tb> metastasis <SEP> associated <SEP> 1 <SEP> Hs. <SEP> 101448
<tb> microsomal <SEP> glutathione <SEP> S-transferase <SEP> 1 <SEP> Hs. <SEP> 790
<tb> minichromosome <SEP> maintenance <SEP> deficient <SEP> (S. <SEP> cerevisiae) <SEP> 2 <SEP> (mitotin) <SEP> Hs. <SEP> 57101
<tb> mucin <SEP> 1 <SEP> Hs. <SEP> 89603
<tb> multifunctional <SEP> polypeptide <SEP> similar <SEP> to <SEP> SAICAR <SEP> synthetase <SEP> and <SEP> AIR <SEP> carboxylase <SEP> Hs. <SEP> 117950
<Tb>

<Desc / Clms Page number 29>

<Tb>
<tb> mut <SEP> L <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 1 <SEP> (colon <SEP> cancer, <SEP> nonpolyposis <SEP> type <SEP> 2) <SEP> Us. <SEP> 57301
<tb> mut <SEP> S <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 3 <SEP> Hs. <SEP> 42674
<tb> N-acetyltransferase <SEP> 1 <SEP> (arylamine <SEP> N-acetyltransferase) <SEP> Hs. <SEP> 155956
<tb> neutrophil <SEP> cytosolic <SEP> factor <SEP> 1 <SEP> (47kD, <SEQ> chronic <SEP> granulomatous <SEP> disease, <SEP> autosomal <SEP> 1) <SEP> Hs. <SEP> 1583
<tb> N-myc <SEP> downstream <SEP> regulated <SEP> Hs. <SEP> 75789
<tb> non-metastatic <SEP> cells <SEP> 1, <SEQ> protein <SEP> (NM23A) <SEP> expressed <SEP> in <SEP> Hs. <SEP> 118638
<tb> non-POU-domain <SEP> containing, <SEP> octamer <SEP> binding <SEP> Hs. <SEP> 172207
<tb> nuclear <SEP> receptor <SEP> coactivator <SEP> 3 <SEP> Hs. <SEP> 225977
<tb> nuclear <SEP> transcription <SEP> factor, <SEP> Xbox <SEP> binding <SEP> 1 <SEP> Hs. <SEP> 3187
<tb> nucleophosmin <SEP> (nucleolar <SEP> phosphoprotein <SEP> B23, <SEP> numatrin) <SEP> Hs. <SEP> 173205
<tb> osteoblast <SEP> specific <SEP> factor <SEP> 2 <SEP> (fasciclin <SEP> I-like) <SEP> Hs. <SEP> 136348
<tb> parvalbumin <SEP> Hs.295449
<tb> pescadillo <SEP> (zebrafish) <SEP> peer <SEP> 1 <SEP> containing <SEP> BRCT <SEP> domain <SEP> Hs.13501
<tb> phosphofructokinase, <SEP> platelet <SEP> Hs. <SEP> 99910
<tb> phospholemman <SEP> Hs. <SEP> 160318
<tb> phospholipase <SEP> A2, <SEP> group <SEP> IIA <SEP> (platelets, <SEP> synovial <SEP> fluid) <SEP> Hs.76422
<tb> phospholipid <SEP> scramblase <SEP> 1 <SEP> Hs.198282
<tb> pituitary <SEP> tumor-transforming <SEP> 1 <SEP> Hs. <SEP> 181195
<tb> plakoglobm <SEP> Hs. <SEP> 2340
<tb> plasminogen <SEP> Hs. <SEP> 75576
<Tb>

<Desc / Clms Page number 30>

<Tb>
<tb> plasminogen <SEP> activator <SEP> inhibitor <SEP> 1 <SEP> Hs. <SEP> 82085
<tb> platelet / endothelial <SEP> cell <SEP> adhesion <SEP> molecule <SEP> (CD31 <SEP> antigen) <SEP> Hs.78146
<tb> platelet-derived <SEP> growth <SEP> factor <SEP> receptor, <SEP> beta <SEP> polypeptide <SEP> Hs.76144
<tb> 1 <SEP> polo <SEP> (Drosophia) <SEP> -like <SEP> kinase <SEP> Hs. <SEP> 77597
<tb> polymyositis / scleroderma <SEP> autoantigen <SEP> 1 <SEP> (75kD) <SEP> Hs. <SEP> 91728
<tb> 1 <SEP> postmeiotic <SEP> segregation <SEP> increased <SEP> 2-like <SEP> 3 <SEP> Hs. <SEP> 278467
<tb> potassium <SEP> intermediate / small <SEP> conductance <SEP> calcium-activated <SEP> channel, <SE>> subfamily <SEP> N, <SEP> member <SEP> 4 <SEP> Hs. <SEP> 10082
<tb> POU <SEP> domain, <SEP> class <SEP> 2, <SEP> transcription <SEP> factor <SEP> 2 <SEP> Hs. <SEP> 1101
<tb> primase, <SEP> polypeptide <SEP> 1 <SEP> (49kD) <SEP> Hs. <SEP> 82741
<tb> Progesterone <SEP> receptor <SEP> Hs. <SEP> 2905
<tb> prohibitin <SEP> Hs.75323
<tb> prolactin <SEP> Hs.1905
<tb> prolactin-induced <SEP> protein <SEP> Hs.99949
proliferating SEP cell nuclear SEP antigen SEP Hs.78996
<tb> proliferation-associated <SEP> 2G4, <SEP> 38kD <SEP> Hs.5181
<tb> protease <SEP> inhibitor <SEP> 12 <SEP> (neuroserpin) <SEP> Hs.78589
<tb> protease, <SEP> serine, <SEP> 8 <SEP> (prostasin) <SEP> Hs.75799
<tb> 1 <SEP> proteasome <SEP> (prosome <SEP> macropain) <SEP> 26S <SEP> subunit, <SEP> non-ATPase, <SEP> 12 <SEP> Hs. <SEP> 4295
<tb> protein <SEP> phosphatase <SEP> 1, <SEP> catalytic <SEP> subunit, <SEP> beta <SEP> isoform <SEP> Hs. <SEP> 21537
<tb> protein <SEP> tyrosine <SEP> kinase <SEP> 6 <SEP> Hs. <SEP> 51133
<Tb>

<Desc / Clms Page number 31>

<Tb>
<tb> purinergic <SEP> receptor <SEP> P2X, <SEP> ligand-gated <SEP> ion <SEP> channel, <SEP> 4 <SEP> Hs. <SEP> 321709
<tb> RAD51 <SEP> Hs.343807
<tb> RAD54 <SEP> (S. <SEP> cerevisiae) <SEP> -1ike <SEP> Hs. <SEP> 66718
<tb> RAP2A <SEP> member <SEP> of <SEP> ras <SEP> oncogen <SEP> family <SEP> Hs.301746
<tb> ras <SEP> peer <SEP> gene <SEP> family <SEP> member <SEP> B <SEP> (rhoB) <SEP> Hs.204354
<tb> ras <SEP> peer <SEP> gene <SEP> family, <SEP> member <SEP> H <SEP> Hs. <SEP> 109918
<tb> regulator <SEP> of <SEP> G-protein <SEP> signaling <SEP> 5 <SEP> Hs.24950
<tb> replication <SEP> factor <SEP> C <SEP> (activator <SEP> 1) <SEP> 4 <SEP> (37kD) <SEP> Hs.35120
<tb> RERG <SEP> (ds <SEP><SEP> EST Collection) <SEP> Hs. <SEP> 21594
<tb> retinoblastoma-like <SEP> 2 <SEP> (p <SEP> 130) <SEP> Hs. <SEP> 79362
<tb> retinoic <SEP> acid <SEP> receptor <SEP> responder <SEP> (tazarotene <SEP> induced) <SEP> 1 <SEP> Hs. <SEP> 82547
<tb> retinol-binding <SEP> protein <SEP> 4, <SEP> interstitia1 <SEP> Hs. <SEP> 76461
<tb> ribonucleotide <SEP> reductase <SEP> M1 <SEP> polypeptide <SEP> Hs. <SEP> 2934
<tb> ribosomal <SEP> protein <SEP> L13 <SEP> Hs. <SEP> 180842
<tb> S <SEP> 100 <SEP> calcium <SEP> binding <SEP> pronein <SEP> A4 <SEP> Hs. <SEP> 81256
<tb> S100 <SEP> calcium-binding <SEP> protein <SEP> A2 <SEP> Hs. <SEP> 38991
<tb> S100 <SEP> calcium-binding <SEP> protein <SEP> A8 <SEP> Hs. <SEP> I00000
<tb> S <SEP> 100 <SEP> calcium-binding <SEP> protein <SEP> A9 <SEP> (calgranulin <SEP> B) <SEP> Hs. <SEP> 112405
<tb> S100 <SEP> calcium-binding <SEP> protein <SEP> P <SEP> Hs. <SEP> 2962
<tb> S <SEP> 100 <SEP> calcium-binding <SEP> protein, <SEP> beta <SEP> (neural) <SEP> Hs. <SEP> 83384
<Tb>

<Desc / Clms Page number 32>

<Tb>
<tb> secreted <SEP> frizzled <SEP> related <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 7306
<tb> secretory <SEP> leukocyte <SEP> protease <SEP> inhibitor <SEP> (qntileukoproteinase) <SEP> Hs. <SEP> 251754
<tb> selenium <SEP> binding <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 334841
<tb> SELENOPHOSPHATE <SEP> SYNTHETASE <SEP>;<SEP> Human <SEP> selenium <SEP> donor <SEP> protein <SEP> Hs. <SEP> 118725
<tb> serine <SEP> proteinase <SEP> inhibitor, <SEP> clade <SEP> B, <SEP> member <SEP> 5 <SEP> (maspin) <SEP> Hs. <SEP> 55279
<tb> serine / threonine <SEP> kinase <SEP> 15 <SEP> Hs. <SEP> 48915
<tb> serum <SEP> constitute <SEP> protein <SEP> Hs. <SEP> 148101
<tb> singed <SEP> (Drosophila) -like <SEP> (sea <SEP> urchin <SEP> fascinate <SEP> homolog <SEP> like) <SEP> Hs. <SEP> 118400
<tb> small <SEP> inducible <SEP> cytokine <SEP> subfamily <SEP> A <SEP> (Cys-Cys), <SEP> member <SEP> 18, <SEP> pulmonary <SEP> and <SEP> activationregulated <SEP> Hs.16530
<tb> small <SEP> inducible <SEP> cytokine <SEP> subfamily <SEP> D <SEP> (Cys-X3-Cys), <SEP> member <SEP> 1 <SEP> (fractalkine, <SEP> neurotactin) <SEP> Hs.80420
<tb> small <SEP> nuclear <SEP> ribonucleoprotein <SEP> polypeptide <SEP> B "Hs. <SEP> 82575
<tb> solute <SEP> carrier <SEP> family <SEP> 7 <SEP> (cationic <SEP> amino <SEP> acid <SEP> transport, <SEP> y + <SEP> system), <SEP> member <SEP > 5 <SEP> Hs. <SEP> 184601
<tb> solute <SEP> carrier <SEP> family <SEP> 9 <SEP> (sodium / hydrogen <SEP> exchanger), <SEP> isoform <SEP> 3 <SEP> regulatory <SEP> factor <SEP> 1 <SEP> Hs. <SEP> 184276
<tb> splicing <SEP> factor, <SEP> arginine / serine-rich <SEP> 5 <SEP> Hs. <SEP> 166975
<tb> stanniocalcin <SEP> 2 <SEP> Hs. <SEP> 155223
<tb> superoxide <SEP> dismutase <SEP> 3, <SEP> extracellular <SEP> Hs. <SEP> 2420
<tb> delete <SEP> oftumorogenicity <SEP> Hs. <SEP> 56937
<tb> suppression <SEP> of <SEP> tumorogenicity <SEP> Hs. <SEP> 301974
<tb> T-cell <SEP> receptor, <SEP> beta <SEP> cluster <SEP> Hs. <SEP> 2003
<tb> T-cell <SEP> receptor, <SEP> delta <SEP> (V, <SEP> D, <SEP> J, <SEP> C) <SEP> Hs. <SEP> 2014
<Tb>

<Desc / Clms Page number 33>

<Tb>
<tb> TEK <SEP> tyrosine <SEP> kinase, <SEP> endothelial <SEP> (venous <SEP> malformations, <SEP> multiple <SEP> cutaneous <SEP> and <SEP> mucosan <SEP> Hs. <SEP > 89640
<tb> Telomerase <SEP> reverse <SEP> transcriptase <SEP> Hs. <SEP> 115256
<tb> TGFBl-induced <SEP> anti-apoptotic <SEP> factor <SEP> I <SEP> Hs. <SEP> 75822
<tb> thrombospondin <SEP> 1 <SEP> Hs. <SEP> 87409
<tb> Thy-1 <SEP> cell <SEP> surface <SEP> antigen <SEP> Hs. <SEP> 125359
<tb> thymidylate <SEP> synthetase <SEP> Hs. <SEP> 82962
<tb> tissue <SEP> factor <SEP> pathway <SEP> inhibitor <SEP> (lipoprotein-associated <SEP> coagulation <SEP> inhibitor) <SEP> Hs.170279
<tb> tissue <SEP> inhibitor <SEP> of <SEP> metalloproteinase <SEP> 1 <SEP> (erythroid <SEP> potentiating <SEP> activity, <SEP> collagenase <SEP> inhibitor) <SEP> Hs.5831
<tb> tissue <SEP> inhibitor <SEP> of <SEP> metalloproteinase <SEP> 3 <SEP> Hs. <SEP> 245188
<tb> TNF <SEP> associated <SEP> factor <SEP> 4 <SEP> Hs. <SEP> 8375
<tb> TNF <SEP> receptor-associated <SEP> factor <SEP> 6 <SEP> Hs. <SEP> 90957
<tb> topoisomerase <SEP> (DNA) <SEP> II <SEP> alpha <SEP> (170kD) <SEP> Hs. <SEP> 156346
<tb> topoisomerase <SEP> (DNA) <SEP> II <SEP> beta <SEP> (180kD) <SEP> Hs. <SEP> 75248
<tb> TP53 <SEP> Hs. <SEP> 149923
<tb> transcription <SEP> factor <SEP> AP-2 <SEP> alpha <SEP> (activating <SEP> enhancer-binding <SEP> protein <SEP> 2 <SEP> alpha) <SEP> Hs. <SEP> 18387
<tb> Transforming SEP> growth <SEP> factor, <SEP> alpha <SEP> Hs. <SEP> 170009
<tb> transfonning <SEP> growth <SEP> factor, <SEP> beta <SEP> receptor <SEP> III <SEP> (betaglycan, <SEP> 300kD) <SEP> Hs. <SEP> 79059
<tb> translin <SEP> Hs. <SEP> 75066
<tb> Trefoil <SEP> factor <SEP> 1 <SEP> (breast <SEP> cancer, <SEP> estrogen-inducible <SEP> sequence <SEP> expressed <SEP> in) <SEP> Hs. <SEP> 1406
<tb> trophinin-assisting <SEP> protein <SEP> (tastin) <SEP> Hs. <SEP> 171955
<Tb>

<Desc / Clms Page number 34>

<Tb>
<tb> troponin <SEP> I, <SEP> skeletal, <SEP> fast <SEP> Hs. <SEP> 83760
<tb> tryptophanyl-tRNA <SEP> synthetaseHs. <SEP> 82030
<tb> tyrosine <SEP> kinase <SEP> withimmunoglobulin <SEP> and <SEP> EGF <SEP> homology <SEP> domains <SEP> Hs.78824
<tb> Tyrosyl-tRNA <SEP> Synthetase <SEP> Hs.239307
<tb> UDP-galactose <SEP> transport <SEP> related <SEP> Hs. <SEP> 154073
<tb> UDP-N-acetyl-aIpha-D-ga <SEP>! <SEP> actosamme3Hs. <SEP> 278611
<tb> uracil-DNA <SEP> glycosylase <SEP> Hs. <SEP> 78853
<tb> uridine <SEP> monophosphate <SEP> synthetase <SEP> (orotate <SEP> phosphoribosyl <SEP> transferase <SEP> and <SEP>orotidine-5'decarboxylase)<SEP> Hs. <SEP> 2057
<tb> v-erb-b2 <SEP> avian <SEP> erythroblastic <SEP> leukemia <SEP> viral <SEP> oncogene <SEP> homolog <SEP> 2 <SEP> Hs. <SEP> 323910
<tb> very <SEP> low <SEP> density <SEP> lipoprotein <SEP> receptor <SEP> Hs. <SEP> 73729
<tb> v-Ha-ras <SEP> Harvey <SEP> rat <SEP> sarcoma <SEP> viral <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 37003
<tb> vimentin <SEP> Hs. <SEP> 297753
<tb> v-jun <SEP> avian <SEP> sarcoma <SEP> virus <SEP> 17 <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 78465
<tb> v-myb <SEP> avian <SEP> myeloblastosis <SEP> viral <SEP> oncogene <SEP> homolog-like <SEP> 2 <SEP> Hs. <SEP> 179718
<tb> v-myc <SEP> avian <SEP> myelocytomatosis <SEP> viral <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 79070
<tb> von <SEP> Willebrand <SEP> factor <SEP> Hs. <SEP> 110802
<tb> WNT1 <SEP> inducible <SEP> signaling <SEP> pathway <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 194679
<tb> X-box <SEP> binding <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 149923
<tb> Zinc <SEP> finger <SEP> protein <SEP> 147 <SEP> (estrogen-responsive <SEP> finger <SEP> protein) <SEP> Hs. <SEP> 1579
<tb> Zinc <SEP> Finger <SEP> Protein <SEP> 161 <SEP> Hs. <SEP> 167558
<Tb>

<Desc / Clms Page number 35>

<Tb>
<tb> zing <SEP> Finger <SEP> Protein <SEP> 217 <SEP> Hs <SEP> 155040
<Tb>

<Desc / Clms Page number 36>

<Tb>
<tb> ANNEX <SEP> 2 <SEP> SEQ <SEP> 2
<Tb>
DNA LESION REPAIR MODULE: 130 PROBES
MOLECULAR

<Tb>
<tb> Name <SEP> of the <SEP> gene <SEP> Unigene
<tb> 8-oxoguanine <SEP> DNA <SEP> lycosylase <SEP> Hs.96398
<tb> ADP-ribosyltransferase <SEP> (NAD +; <SEP> poly <SEP> (ADP-ribose) <SEP>polymerase);<SEP> poly <SEP> (ADP-ribose)
<tb> polymerase <SEP> Hs. <SEP> 177766
<tb> ADP-ribosyltransferase <SEP> (NAD +; <SEP> poly <SEP> (ADP-ribose) <SEP> polymerase) -like <SEP> 2 <SEP> Hs.24284
<tb> alkylation <SEP> DNA <SEP> repair <SEP> protein <SEP> alkb <SEP> homolog <SEP> Hs. <SEP> 54418
<tb> APEX <SEP> nuclease <SEP> (multifunctional <SEP> DNA <SEP> repair <SEP> enzyme) <SEP>;<SEP> apurinic / apyridinic <SEP> (abasic) <SEP> endonuclease <SEP> Hs. <SEP> 73722
<tb> apurinic / apyrimidinic <SEP> endonuclease <SEP> (APEX <SEP> nuclease) -like <SEP> 2 <SEP> protein <SEP> Hs. <SEP> 154149
<tb> ataxia <SEP> telangiectasia <SEP> and <SEP> Rad3 <SEP> related <SEP> Hs. <SEP> 77613
<tb> ataxia <SEP> telangiectasia <SEP> mutated <SEP> (includes <SEP> complementation <SEP> groups <SEP> A <SEP> C <SEP> and <SEP> D) <SEP> Hs. <SEP> 194382
<tb> ataxia <SEP> telangiectasia <SEP> mutated <SEP> (includes <SEP> complementation <SEP> groups <SEP> A <SEP> C <SEP> and <SEP> D) <SEP> Ha. <SEP> 194382
<tb> Bloom <SEP> syndrome <SEP> Hs. <SEP> 36820
<tb> breast <SEP> cancer <SEP> 1, <SEP> early <SEP> onset <SEP> Hs. <SEP> 194143
<tb> breast <SEP> cancer <SEP> 2, <SEP> early <SEP> onset <SEP> Hs. <SEP> 34012
<Tb>

<Desc / Clms Page number 37>

<Tb>
<tb> caltractin <SEP> (20kD <SEP> calcium-binding <SEP> protein) <SEP>;<SEP> centrin, <SEP> EF-hand <SEP> protein, <SEP> 2Hs. <SEP> 82794
<tb> CHK1 <SEP> (checkpoint, <SE> S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 20295
<tb> CHK2 <SEP> check <SEP> anoint <SEP> S <SEP> ombe <SEP> homolo <SEP> Hs. <SEP> 146329
<tb> Cockayne <SEP> syndrome <SEP> 1 <SEP> (classica <SEP>!) <SEP> Hs. <SEP> 32967
<tb> cyclin <SEP> H <SEP> Hs.514
<tb> cyclin-dependentkinase <SEP> 7 <SEP> (homolog <SEP> ofXenopus <SEP> MO <SEP> 15 <SEP> cdk-activatingkinase) <SEP> Hs. <SEP> 184298
<tb> damage-specific <SEP> DNA <SEP> binding <SEQ ID> protein <SEP> 1 <SEP> (48kD) <SEQ> Hs.108327
<tb> damage-specific <SEP> DNA <SEP> protein binding <SEP> protein <SEP> 2 <SEP> (48kD) <SEQ> Hs.77602
<tb> DMC1Hs. <SEP> 37181
<tb> dUTP <SEP> pyrophosphataseHs. <SEP> 82113
<tb> ESTs / human <SEP> p53 <SEP> R2 <SEP> gene <SEP> for <SEP> ribonucleotide <SEP> reductase <SEP> Hs. <SEP> 94262
<tb> ESTs, <SEP> Weakly <SEP> similar <SEP> to <SEP> DNA <SEP> NUCLEOTIDYLEXOTRANSFERASE <SEP> [H. <SEP> sapiens] / similar
<tb> to <SEP> DNA <SEP> polymerase <SEP> Hs. <SEP> 46964
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> compleme-ntation <SEP> group
<tb> (xeroderma <SEP> Pigmentosa <SEP> group <SEP> D <SEP> complementing) <SEP> Hs.99987
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 1
<tb> Hs.59544
<tb> (includes <SEP> overlapping <SEP> antisense <SEP> sequence)
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 3
<tb> Hs.77929
<tb> (xeroderma <SEP> pigmentosum <SEP> group <SEP> B <SEP> complementing)
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> complementation <SEP> group <SEP> 4 <SEP> Hs. <SEP> 89296
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 5
<tb> (xeroderma <SEP> pigmentosum, <SEP> supplementation <SEP> group <SEP> G <SEP> (Cockayne <SEP> syndrome) <SEP>) <SEP> Hs. <SEP> 48576
<tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> complementation <SEP> group <SEP> 6 <SEP> Hs. <SEP> 99924
<tb> exonuclease <SEP> I <SEP> Hs. <SEP> 47504
<tb> Fanconi <SEP> anemia, <SEP> complementation <SEP> group <SEP> A <SEP> Hs. <SEP> 86297
<Tb>

<Desc / Clms Page number 38>

<Tb>
<tb> Fanconi <SEP> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> C <SEP> Hs.37953
<tb> Fanconi <SEP> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> D1
<tb> Fanconi <SEP> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> D2 <SEP> Hs.15607
<tb> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> E <SEP> Hs.302003
<tb> Fanconi <SEP> anemia, <SEP> complementation <SEP> group <SEP> F <SEP> Hs. <SEP> 65328
<tb> Fanconi <SEP> anemia, <SEP> complementation <SEP> group <SEP> G <SEP> Hs. <SEP> 8047
<tb> flap <SEP> structure-specific <SEP> endonuclease <SEP> 1 <SEP> Hs. <SEP> 4756
<tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 1 <SEP> (62kD <SEP> subunit) <SEP> Hs. <SEP> 89578
<tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 2 <SEP> (30kD <SEP> subunit) <SEP> Hs. <SEP> 191356
<tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 3 <SEP> (34kD <SEP> subunit) <SEP> Hs. <SEP> 90304
<tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 4 <SEP> (52kD <SEP> subunit) <SEP> Hs. <SEP> 102910
<tb> H2A <SEP> histone <SEP> family, <SEP> member <SEP> X <SEP> Hs. <SEP> 147097
<tb> HCNP <SEP> protein <SEP>;<SEP> XPA-binding <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 9822
<tb> Homo <SEP> sapiens <SEP> mRNA <SEP>;<SEP> cDNA <SEP> DKFZp586G1122 <SEP> (from <SEP> clone <SEP> DKFzp586G1122) <SEP> (MRE11A) <SEP> Hs. <SEP> 20555
<tb> HUS1 <SEP> (S. <SEP> pombe) <SEP> checkpoint <SEP> peer <SEP> Hs.152983
<tb> KIAA0086 <SEP> gene <SEP> product <SEP> Hs.1560
<tb> ligase <SEP> I, <SEP> DNA, <SEP> AT <SEP> P-dependent <SEP> Hs.1770
<tb> ligase <SEP> III, <SEQ> DNA, <SEP> ATP-dependetn <SEP> Hs.100299
<tb> Ii <SEP> ase <SEP> 1 <SEP> DNA, <SEQ ID> ATP-dependent <SEP> Hs.166091
<Tb>

<Desc / Clms Page number 39>

<Tb>
<tb> household <SEP> a <SEP> three <SEP> I <SEP><SEP><SEP> assembly <SEP> Fs <SEP> 32380
<tb> methyl-CpG <SEP> binding <SEP> domain <SEP> protein <SEP> 4 <SEP> Hs. <SEP> 35947
<tb> mitotic <SEP> arrest <SEP> defiance, <SEP> yeast, -like2 <SEP> Hs. <SEP> 19400
<tb> MMS19 <SEP> (MET18 <SE> S. <SEP> cerevisiae) - <SEP> like <SEP> Hs. <SEP> 288891
<tb> mutL <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 1 <SEP> (colon <SEP> cancer, <SEP> nonpolyposis <SEP> type <SEP> 2) <SEP> Hs . <SEP> 57301
<tb> mutL <SEP> (E. coli) <SEP> homolog3 <SEP> Hs.279842
<tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 3 <SEP> Hs. <SEP> 42674
<tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 4 <SEP> Hs.115246
<tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 5 <SEP> Hs.112193
<tb> muts <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 5 <SEP> Hs. <SEP> 112193
<tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 2Hs. <SEP> 78934
<tb> muts <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 6 <SEP> Hs. <SEP> 3248
<tb> mutY <SEP> (E. <SEP> coli) <SEP> homologHs. <SEP> 271353
<tb> Nijmegen <SEP> breage <SEP> syndrome <SEP> 1 <SEP> (nibrin) <SEP> Hs.25812
<tb> N-methylpurine-DNA <SEP> glycosylase <SEP> Hs.79396
<tb> nth <SEP> (E. <SEP> coli <SEP> endonuclease <SEP> III <SEP> -1i <SEP> 1 <SEP> Hs. <SEP> 66196
<tb> nudix <SEP> * (nucleoside <SEP> diphosphate <SEP> linked <SEP> moiety <SEP> X) -type <SEP> pattern <SEP> 1 <SEP> Hs. <SEP> 388
<tb> 0-6-meth <SEP> 1 <SEP> anine-DNA <SEP> meth <SEP> ltransferase <SEP> Hs. <SEP> 1384
<tb> polymerase <SEP> (DNA <SEP> directed) <SEP> eta <SEP> Hs.155573
<tb> polymerase <SEP> (DNA <SEP> direct) <SEP> gamma <SEP> Hs.80961
<Tb>

<Desc / Clms Page number 40>

<Tb>
<tb> polymerase <SEP> (DNA <SEP> directed) <SEP> iota <SEP> Hs. <SEP> 271699
<tb> polymerase <SEP> (DNA <SEP> directed) <SEP> kappa <SEP> Hs. <SEP> 135756
<tb> polymerase <SEP> (DNA <SEP> directed) <SEP> lambda <SEP> Hs.129903
<tb> polymerase <SEP> (DNA <SEP> directed) <SEP> lambda <SEP> Hs.225951
<tb> polymerase <SEP> (DNA <SEP> directed), <SEP> beta <SEP> Hs. <SEP> 180107
<tb> polymerase <SEP> (DNA <SEP> directed), <SEP> delta <SEP> 1, <SEP> catalytic <SEP> subunit <SEP> (125kD) <SEP> Hs.99890
<tb>polymerase'DNA<SEP> directed), <SEP> epsilon <SEP> Hs. <SEP> 166846
<tb> polynucleotide <SEP> kinase <SEP>3'phosphatase<SEP> Hs. <SEP> 78016
<tb> postmeiotic <SEP> segregation <SEP> increased <SEP> (S. <SEP> cerevisiae) <SEP> 1 <SEP> Us. <SEP> 111749
<tb> postmeiotic <SEP> segregation <SEP> increased <SEP> (S. <SEP> cerevisiae) <SEP> 2 <SEP> Hs. <SEP> 177548
<tb> postmeiotic <SEP> ss <SEP> increased <SEP> 2- <SEP>! <SEP> ike <SEP> 3 <SEP> Hs. <SEP> 278467
<tb> postmeiotic <SEP> segregation <SEP> increased <SEP> 2-like <SEP> 4 <SEP> Hs. <SEP> 278468
<tb> proliferating <SEP> cell <SEP> nuclear <SEP> antigen <SEP> Hs. <SEP> 78996
<tb> protein <SEP> kinase, <SEP> DNA-activated, <SEP> catalytic <SEP> polypeptide <SEP> Hs.155637
<tb> RAD1 <SEP> (S. <SEP> pombe) <SEP> peer <SEP> Hs.7179
<tb> RAD18 <SEP> Hs.21320
<tb> RAD23 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> AHs. <SEP> 180455
<tb> RAD23 <SEP> (S. <SEP> cerevisiae) <SEP> peer <SEP> B <SEP> Hs. <SEP> 178658
<tb> RAD50 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs.41587
<tb> RAD51 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> (E <SEP> coli <SEP> RecA <SEP> homolog) <SEP> Hs.1253667
<Tb>

<Desc / Clms Page number 41>

<Tb>
<tb> RAD51 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> C <SEP> Hs. <SEP> 11393
<tb> RAD51L1Hs. <SEP> 100669
<tb> RAD51L3 <SEP> Hs. <SEP> 125244
<tb> RAD52 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs. <SEP> 89571
<tb> RAD54 <SEP> (S. <SEP> cerevisiae) -like <SEP> Hs. <SEP> 66718
<tb> RAD54B <SEP> Hs. <SEP> 128501
<tb> RAD9 <SEP> (S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 240457
<tb> RecQ <SEP> protein-like <SEP> 4 <SEP> Hs. <SEP> 31442
<tb> replication <SEP> protein <SEP> Al <SEP> (70kD) <SEP> / GS2 <SEP> gene <SEP> (= C9) <SEP> Hs. <SEP> 84318
<tb> replication <SEP> protein <SEP> A2 <SEP> (32kD) <SEP> Hs. <SEP> 79411
<tb> replication <SEP> protein <SEP> A2 <SEP> (32kD) <SEP> Hs. <SEP> 79411
<tb> replication <SEP> protein <SEP> A3 <SEP> (14kD) <SEP> Hs. <SEP> 1608
<tb> REV1 <SEP> (yeast <SEP> peer) - <SEP> like <SEP> Hs. <SEP> 110347
<tb> REV3 <SEP> (yeast <SEP> homolog) -like, <SEP> catalytic <SEP> subunit <SEP> of <SEP> DNA <SEP> polymerase <SEP> zeta <SEP> Hs. <SEP> 115521
<tb> single-strand <SEP> monofunctional <SEP> uracil <SEP> DNA <SEP> glycosylase <SEP> Hs. <SEP> 5212
<tb> SP011, <SEP> meiotic <SEP> protein <SEP> covalently <SEP> bound <SEP> to <SEP> DSB <SEP> (S-cerevisiae) <SEP> -1ike <SEP> Hs. <SEP> 159737
<tb> three <SEP> time <SEP> repair <SEP> exonuclease <SEP> 1 <SEP> Hs. <SEP> 278408
<tb> three <SEP> time <SEP> repair <SEP> exonuclease <SEP> 2 <SEP> Hs. <SEP> 251398
<tb> thymidine-DNA <SEP> glycosylase <SEP> Hs.173824
<tb> thyroid <SEP> autoantigen <SEP> 70kD <SEP> (Ku <SEP> antigen) <SEP> Hs.197345
<Tb>

<Desc / Clms Page number 42>

<Tb>
<tb> topoisomerase <SEP> related <SEP> function <SEP> protein <SEP> 4-2 <SEP> Hs. <SEP> 294030
<tb> tumor <SEP> protein <SEP> 53-binding <SEP> protein, <SEP> 1 <SEP> Hs. <SEP> 170263
<tb> ubiquitin <SEP> activating <SEP> enzyme-2 <SEP> Hs. <SEP> 16695
<tb> ubiquitin-conjugating <SEP> enzyme <SEP> E2A <SEP> (RAD6 <SEP> homolog) <SEP> Hs. <SEP> 80612
<tb> ubiquitm-conjugating <SEP> enzyme <SEP> E2A <SEP> variant <SEP> 2 <SEP> Hs. <SEP> 79300
<tb> ubiquitin-conjugating <SEP> enzyme <SEP> E2N <SEP> (homologous <SEP> to <SEP> yeast <SEP> UBC13) <SEP> Hs. <SEP> 75355
<tb> uracil-DNA <SEP> glycosylase <SEP> Hs. <SEP> 78853
<tb> Wemer <SEP> syndrome <SEP> Hs. <SEP> 150477
<tb> xeroderma <SEP> pigmentosum, <SEP> supplementation <SEP> group <SEP> A <SEP> Hs. <SEP> 192803
<tb> xeroderma <SEP> pigmentosum, <SEP> complementation <SEP> group <SEP> C <SEP> Hs. <SEP> 320
<tb> X-ray <SEP><SEP> repair <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 1 <SEP> Hs. <SEP> 98493
<tb> X-ray <SEP><SEP> repairing <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 2 <SEP> Hs. <SEP> 129727
<tb> X-ray <SEP><SEP> repair <SEP> defective <SEP> repair <SEP><SEP> Chinese <SEP> Hamster <SEP> cells <SEP> 3 <SEP> Hs. <SEP> 99742
<tb> X-ray <SEP><SEP> repair <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 4 <SEP> Hs. <SEP> 150930
<tb> X-ray <SEP> repair <SEP> complementing <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 5 <SEP> (double-strand- break
<tb> rejoining <SEP>;<SEP> Ku <SEP> autoantigen, <SEP> 80kD) <SEP> Hs. <SEP> 84981
<Tb>

Claims (45)

CLAIMS 1 Biochips characterized in that they comprise, on at least one support, at least one molecular probe which is: high purity in known quantity deposited on said support; and wherein the molecular probe: refers to all or a fragment of DNA, or cDNA, characteristic of a given gene and meeting the three requirements which have just been specified, or of high purity. "or of very high purity" means that the molecular probe is freed from all chemical reagents, free oligonucleotides, and nucleotide fragments which do not correspond to the probe (probe fragments and / or primers or primers), or in known quantity means that one has access to the precise quantity deposited because it results from a deposit on the support of a known volume of starting suspension, itself of known concentration, and where identified in its nucleotide sequence means more precisely identified in its nucleotide sequence informative to the functions of the gene, which in turn means that we have proceeded to the identification of the sequence of the genes. its nucleotides corresponding to all or part of an identified gene, where all or part means the minimum number of bases sufficient to define the specificity of a gene (or length of the sequence verified). <Desc / Clms Page number 44>  2 biochips according to claim 1 characterized in that they are thematic biochips of very high quality ". 3 biochips according to claim 1 characterized in that they are biochips screening very high quality. 4 biochips according to claim 1 characterized in that they comprise a combination of several thematic molecular probes of very high quality. 5 microarrays according to claim 1 characterized in that they comprise a combination of at least one thematic molecular probe of very high quality and at least one molecular screening probe of very high quality. 6 microarrays according to claim 1 characterized in that they comprise a combination of at least one thematic molecular probe and at least one molecular screening probe and in that at least one of these probes is a molecular probe of very high quality. 7 biochips according to claim 6 characterized in that all the molecular probes used are of very high quality. 8 microarrays according to claim 1 or 2: characterized in that they are thematic biochips and comprise a combination of special molecular probes adapted to include genes whose expression gives an indication on the tumor tissue (stage of the tumor, its aggressiveness, the affected cells, the invasiveness, the resistance or, on the contrary, the sensitivity to anti-tumor treatments ...). 9 biochips according to claim 1 or 2 characterized in that they are thematic biochips and comprise only a combination of special molecular probes whose expression makes it possible to evaluate the resistance (or the sensitivity) of the tumor to such treatment or to such pharmacological molecule. Biochips according to claim 9, characterized in that they additionally comprise molecular screening probes. 11 biochips according to claim 1 characterized in that they comprise molecular probes screening very high quality <Desc / Clms Page number 45>  and also include a combination of special molecular probes adapted to include genes whose expression gives an indication of the tumor tissue (tumor stage, aggressiveness, affected cells, invasiveness, resistance, or susceptibility to anti-tumor treatments ...).  12 biochips according to claim 6, characterized in that they comprise at least one normal quality screening chip, in addition to one or more thematic biochips and / or screening of very high quality.  13 biochips according to claim 5 characterized in that they comprise at least one thematic biochip of normal quality, in addition to one or more thematic biochips and / or screening of very high quality.  1 4 Biochips of screening, that is to say very high density of genes of very high quality)), characterized in that said biochips comprise all or at least partly high purity molecular probes)).  A method for preparing biochips of the highest quality, of the type according to which at least one molecular probe formed of all or part of genes is deposited on a support, characterized in that it comprises at least one sequence of steps capable of forming at least one molecular probe which is: of high purity in known quantity deposited on said support; identified in its nucleotide sequence ", and capable of being deposited on at least one biochip support, and where molecular probe: denotes all or a fragment of DNA, or cDNA, characteristic of a given gene and responding to all three requirements which have just been specified, where high purity or very high purity means that the molecular probe is free of all chemical reagents, free oligonucleotides, and nucleotide fragments not corresponding to the probe (probe fragments and / or or primers); <Desc / Clms Page number 46>

 1 or in known quantity means that one has access to the precise amount deposited because it results from a deposit on the support of a known volume of starting suspension, itself of known concentration. and where identified in its nucleotide sequence more specifically means identified in its informative nucleotide sequence with respect to the functions of the>> gene, which in turn means that the sequence of the corresponding nucleotide bases has been identified. all or part of an identified gene, where all or part here designates the minimum number of bases sufficient to define the specificity of a gene (or length of the sequence verified "). 1 6 Process according to claim 15 characterized in that it comprises in combination at least one step of assay, dilution and sequencing. Process according to claim 15 or 16, characterized in that it comprises, in combination, at least one purification, assay, dilution and sequencing step. Biochips according to any one of claims 1 to 14, characterized in that said support is selected from glass, a support of a nylon sheet, or a polymer support. 1 9 biochips according to any one of claims 1 to 14 characterized in that said support is selected from: supports for example glass-type, glass-silica, polymers and plastics, or Nylon TM membrane, or any other support spotted "), gene fragments, cDNAs or cDNA fragments, or oligonucleotides, electronic pad surfaces, using the electrostatic attraction of + and- charges, or semiconductor coupled supports, for fixing or depositing the sample nucleic acids. A process according to any one of claims 15 to 17, characterized in that said support is selected from glass, a support of a nylon nylon sheet, or a polymer support.  Method according to any one of Claims 15 to 17, characterized in that said support is chosen from: <Desc / Clms Page number 47>  supports, for example glass, glass-silica, polymers and plastics, or Nylon TM membrane, or any other suitable support, on which are fixed or spotted "gene fragments, cDNAs or fragments of CDNA, or oligonucleotides, electronic pad surfaces, using the electrostatic attraction of + and - charges, or semiconductor coupled supports, for attaching or depositing the sample nucleic acids. The method of any one of claims 15 to 17 and 20, 21 characterized by a combination of the following steps: 1 Extraction of plasmid DNAs. 2 Assay of plasmid DNAs; 3 Dilution of plasmid DNAs.  Amplification of Complementary DNAs (cDNA) or cDNA Fragments or DNA Fragments Purification of the Amplification Products Obtained. 6 Dosage of these products. 7 Dilution at the same concentration. 8 Preparation of a plate where all the cDNAs are at the same amount. 9 Sequencing cDNAs. The method according to any one of claims 15 to 17 and 20 to 22, characterized in that the following steps are carried out: - Obtaining probes from bacterial clones marketed by Incyte TM , with preparation of the probes in 96-well plates, as follows: 1 Extraction of plasmid DNAs.  2 Assay of plasmid DNAs; 3 Dilution of plasmid DNAs.  4 amplification of complementary DNA (cDNA) or cDNA fragments, or DNA fragments, Purification of the amplification products obtained.  6 Dosage of these products. 7 Dilution at the same concentration.  8 Preparation of a plate where all the cDNAs are at the same amount.  9 Sequencing cDNAs. 1 0 Deposit on the glass slide or other support .. <Desc / Clms Page number 48>  Process according to any one of Claims 15 to 17 and 20 to 23, characterized in that the implementation of at least one of its stages, preferably several, and preferably all, is recorded and indexed, including the results of the step or steps involved, in a database, and in that said database contains all or part of the code fragments used for the manufacture of biochips, and ensures the traceability of all the technical steps of gene preparation (technical parameters, batch numbers of reagents used ...). Biochips characterized in that they are obtained by a process according to any one of claims 15 to 18 and 20 to 24. 26 microarrays according to claim 25 characterized in that they comprise the molecular probes listed in Appendix 1 SEQ 1: THEMATIC BIOPUCE: CANCER MAMMARY. 333 MOLECULAR PROBES

<Tb> <tb> Name <SEP> of <SEP> gene <SEP> Unigene <tb> 5T4 <SEP> oncofetal <SEP> trophoblast <SEP> glykoprotein <SEP> Hs. <SEP> 82128 <tb> acid <SEP> phosphatase <SEP> 5, <SEP> t <SEP> artrate <SEP> resistant <SEP> Hs. <SEP> 1211 <tb> actin, <SEP> alpha <SEP> 2, <SEP> smooth <SEP> muscle, <SEP> aorta <SEP> Hs. <SEP> 195851 <tb> activating <SEP> transcription <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 460 <tb> adrenergic, <SEP> beta, <SEP> receptor <SEP> kinase <SEP> l <SEP> Hs. <SEP> 83636 <tb> alcohol <SEP> dehydrogenase <SEP> 2 <SEP> (c1ass <SEP> n, <SEP> beta <SEP> po1peptide <SEP> HsA <tb> aldehyde <SEP> dehydrogenase <SEP> 1, <SEP> soluble <SEP> Hs. <SEP> 76392 <tb> alpha-2-macroglobulin <SEP> Hs. <SEP> 74561 <Tb> <Desc / Clms Page number 49>

<Tb> <tb> androgen <SEP> receptor <SEP> (dihydrotestosterone <SEP> receptor <SEP>; <SEP> testicular <SEP> feminization <SEP>; <SEP> spinal <SEP> and <SEP> bulbar <tb> muscular <SEP> atrophy <SEP>; <SEP> Kennedy <SEP> disease) <SEP> Hs. <SEP> 99915 <tb> annexin <SEP> A <SEP> 1 <SEP> Hs. <SEP> 78225 <tb> annexin <SEP> A8 <SEP> Hs. <SEP> 87268 <tb> antigen <SEP> identified <SEP> by <SEP> monoclonal <SEP> antibody <SEP> Ki-67 <SEP> Hs. <SEP> 80976 <tb> apolipoprotein <SEP> A-I <SEP> Hs. <SEP> 93194 <tb> apolipoprotein <SEP> D <SEP> Hs.75736 <tb> apoptosis <SEP> inhibitor <SEP> 4 <SEP> (survivin) <SEP> Hs.1578 <tb> aquaporin <SEP> 1 <SEP> (channel-forming <SEP> integral <SEP> protein, <SEP> 28kD) <SEP> Hs. <SEP> 74602 <tb> aquaporin <SEP> 7 <SEP> Hs. <SEP> 25475 <tb> armadillo <SEP> repeat <SEP> gene <SEP> deletes <SEP> in <SEP> velocardiofacial <SEP> syndrome <SEP> Hs. <SEP> 171900 <tb> ARP1 <SEP> (actin-related <SEP> protein <SEP> 1, <SEP> yeast) <SEP> homolog <SEP> A <SEP> (centractin <SEP> alpha) <SEP> Hs. <SEP> 2477 <tb> ATP-binding <SEP> cassette, <SEP> sub-family <SEP> C <SEP> (CFTR / MRP), <SEP> member <SEP> 5 <SEP> Hs. <SEP> 108660 <tb> basonuclin <SEP> Hs. <SEP> 64025 <tb> B-cell <SEP> CLL / Lymphoma <SEP> 2 <SEP> Hs. <SEP> 79241 <tb> bcl2 <SEP> associated <SEP> athanogenic <SEP> Hs.41714 <tb> bcl2 <SEP> associated <SEP> X <SEP> protein <SEP> Hs.159428 <tb> beta-2-microglobulinHs. <SEP> 75415 <tb> Brcal <SEP> associated <SEP> RING <SEP> domain <SEP> 1 <SEP> Hs. <SEP> 54089 <tb> breast <SEP> and <SEP> bladder <SEP> overexpressed <SEP> gene <SEP> 1 <SEP> Hs. <SEP> 78768 <tb> Breast <SEP> cancer <SEP> 1, <SEP> early <SEP> onset <SEP> Hs. <SEP> 194143 <Tb> <Desc / Clms Page number 50>

<Tb> <tb> breast <SEP> cancer <SEP> antiestrogen <SEP> resistance <SEP> 1 <SEP> Hs.273219 <tb> breast <SEP> cancer <SEP> antiestrogen <SEP> resistance <SEP> 3 <SEP> Hs.6564 <tb> breast <SEP> cancer <SEP> specic <SEP> genus <SEP> 1 <SEP> or <SEP> synculein <SEP> gamma <SEP> Hs. <SEP> 63236 <tb> budding <SEP> uninhibited <SEP> by <SEP> benzimidazoles <SEP> 1 <SEP> (yeast <SEP> homolog), <SEP> beta <SEP> Hs. <SEP> 36708 <tb> bullous <SEP> pemphigoid <SEP> antigen <SEP> 1 <SEP> (230 / 240kD) <SEP> Hs. <SEP> 620 <tb> butyrate <SEP> response <SEP> factor <SEP> 1 <SEP> (EGF-response <SEP> factor <SEP> 1) <SEP> Hs.85155 <tb> bystin-like <SEP> Hs.106880 <tb> cadherin <SEP> 1 <SEP>; <SEP> E-cadherin <SEP> Hs. <SEP> 194657 <tb> cadherin <SEP> 13 <SEP>; <SEP> H-cadherinHs. <SEP> 63894 <tb> cadherin <SEP> 15'M-cadherin <SEP> Hs. <SEP> 148090 <tb> cadherin <SEP> 3, <SEP> P-cadherin <SEP> (placental) <SEP> Hs. <SEP> 2877 <tb> carboxypeptidase <SEP> B <SEP> 1 <SEP> Hs. <SEP> 180884 <tb> carcinoembryonic <SEP> antigen <SEP> Hs. <SEP> 220529 <tb> cartilage <SEP> oligomeric <SEP> matrix <SEP> protein <SEP> (pseudoachondroplasia, <SEP> epiphyseal <SEP> dysplasia <SEP> 1, <SEP> multiple) <SEP> Hs. <SEP> 1584 <tb> catenin, <SEP> delta <SEP> 1 <SEP> Hs. <SEP> 166011 <tb> cathepsin <SEP> C <SEP> Hs. <SEP> 10029 <tb> cathepsin <SEP> D <SEP> (lysosomal <SEP> aspartyl <SEP> protease) <SEP> Hs. <SEP> 79572 <tb> cathepsin <SEP> Z <SEP> Hs. <SEP> 71388 <tb> caveolin-l <SEP> Hs. <SEP> 323469 <tb> CD2 <SEP> antigen <SEP> (p50), <SEP> sheep <SEP> red <SEP> blood <SEP> cell <SEP> receptor <SEP> Hs. <SEP> 89476 <Tb> <Desc / Clms Page number 51>

<Tb> <tb> CD34 <SEP> anti <SEP> in <SEP> Hs. <SEP> 85289 <tb> CD36 <SEP> antigen <SEP> (collagen <SEP> type <SEP> I <SEP> receptor, <SEP> thrombospondin <SEP> receptor) <SEP> Hs.75613 <tb> CD3D <SEP> antigen, <SEP> delta <SEP> polypeptide <SEP> (TiT3 <SEP> complex) <SEP> Hs. <SEP> 95327 <tb> CD3G <SEP> antigen, <SEP> gamma <SEP> polypeptide <SEP> (TiT3 <SEP> complex) <SEP> Hs.2259 <tb> CD68 <SEP> antigen <SEP> Hs.240615 <tb> CDC28 <SEP> protein <SEP> kinase <SEP> 2 <SEP> Hs. <SEP> 83758 <tb> CDC6 <SEP> (cell <SEP> division <SEP> cycle <SEP> 6, <SE> S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs. <SEP> 69563 <tb> CDC7 <SEP> (cell <SEP> division <SEP> cycle <SEP> 7, <SE> S. <SEP> cerevisiae, <SEP> homolog) -like <SEP> 1 <SEP> Hs. <SEP> 28853 <tb> cell <SEP> division <SEP> cycle <SEP> 20, <SE> S. <SEP> cerevisiae <SEP> homolog <SEP> Hs. <SEP> 82906 <tb> cell <SEP> division <SEP> cycle <SEP> 25C <SEP> Hs. <SEP> 656 <tb> cellular <SEP> retinoic <SEP> acid-binding <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 183650 <tb> centromere <SEP> protein <SEP> E <SEP> (312kD) <SEP> Hs. <SEP> 75573 <tb> centromere <SEP> protein <SEP> F <SEP> (350 / 400kD), <SEP> mitosin) <SEP> Hs. <SEP> 77204 <tb> chitinase <SEP> 1Hs. <SEP> 91093 <tb> chitinase <SEP> 3-like <SEP> 1 <SEP> (cartilage <SEP> glycoprotein-39) <SEP> Hs. <SEP> 75184 <tb> CHK1 <SEP> (checkpoint, <SE> S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 20295 <tb> chromobox <SEP> homolog <SEP> 3 <SEP> (drosophila <SEP> HP1 <SEP> gamma) <SEP> Hs. <SEP> 8123 <tb> collagen, <SEP> type <SEP> I, <SEP> alpha <SEP> 1 <SEP> Hs. <SEP> 172928 <tb> collagen, <SEP> type <SEP> III, <SEP> alpha <SEP> 1 <SEP> (Ehlers-Danlos <SEP> syndrome <SEP> type <SEP> IV, <SEP> autosomal <SEP> dominant ) <SEP> Hs. <SEP> 119571 <tb> collagen, <SEP> type <SEP> VI, <SEP> alpha <SEP> I <SEP> Hs. <SEP> 108885 <Tb> <Desc / Clms Page number 52>

<Tb> <tb> colony <SEP> stimulating <SEP> factor <SEP> 1 <SEP> (macrophage) <SEP> Hs. <SEP> 173894 <tb> CREB <SEP> binding <SEP> protein <SEP> (Rubinstein-Taybi <SEP> syndrome) <SEP> Hs. <SEP> 23598 <tb> cuHin <SEP> 4A <SEP> Hs. <SEP> 183874 <tb> cyclin <SEP> B <SEP> 1 <SEP> Hs. <SEP> 23960 <tb> Cyclin <SEP> D1 <SEP> Hs. <SEP> 82932 <tb> cyclin <SEP> E <SEP> 1 <SEP> Hs. <SEP> 9700 <tb> cyclin <SEP> G1 <SEP> Hs. <SEP> 79101 <tb> Cyclin-dependent <SEP> kinase <SEP> 4 <SEP> Hs. <SEP> 95577 <tb> cyclin-dependent <SEP> kinase <SEP> inhibitor <SEP> 1C <SEP> (p57, <SEP> Kip2) <SEP> Hs. <SEP> 106070 <tb> cystatin <SEP> E / M <SEP> Hs. <SEP> 83393 <tb> cysteine-rich <SEP> protein <SEP> 1 <SEP> (intestinal) <SEP> Hs. <SEP> 17409 <tb> cytochrome <SEP> c <SEP> oxidase <SEP> subunit <SEP> VIe <SEP> Hs. <SEP> 74649 <tb> Cytochrome <SEP> c <SEP> oxidase <SEP> subunit <SEP> VIIa <SEP> polypeptide <SEP> 2 <SEP> like <SEP> Hs. <SEP> 30888 <tb> D123 <SEP> gene <SEP> product <SEP> Hs.82043 <tb> DEAD / H <SEP> (Asp-Glu-Ala-Asp / His) <SEP> box <SEP> polypeptide <SEP> 11 <SEP> (S. <SEP> cerevisiae <SEP> CHLl-1ike <SEP > he1icaseì <SEP> Hs. <SEP> 27424 <tb> density <SEP> regulated <SEP> protein <SEP> Hs. <SEP> 22393 <tb> desmin <SEP> Hs. <SEP> 171185 <tb> dihydrofolate <SEP> reductase <SEP> Hs. <SEP> 83765 <tb> diphtheria <SEP> toxin <SEP> receptor <SEP> (heparin-binding <SEP> epidermal <SEP> growth <SEP> factor-like <SEP> growth <SEP> factor) <SEP> Hs. <SEP> 799 <tb> discointer <SEP> domain <SEP> Receiver <SEP> family, <SEP> member <SEP> 1 <SEP> Hs. <SEP> 75562 <Tb> <Desc / Clms Page number 53>

<Tb> <tb> DNA <SEP> (cytosine-5 -) - methyltransferase <SEP> 1 <SEP> Hs. <SEP> 77462 <tb> dynein, <SEP> axonemal, <SEP> light <SEP> intermediate <SEP> polypeptide <SEP> Hs. <SEP> 33846 <tb> E2F <SEP> transcription <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 1189 <tb> E74-like <SEP> factor <SEP> 3 <SEP> Hs. <SEP> 166096 <tb> early <SEP> development <SEP> regulator <SEP> 2 <SEP> (homolog <SEP> of <SEP> polyhomeotic <SEP> 2) <SEP> Hs. <SEP> 75878 <tb> endoglin <SEP> Hs. <SEP> 76753 <tb> endothelin <SEP> receptor <SEP> type <SEP> B <SEP> Hs. <SEP> 82002 <tb> enhancer <SEP> of <SEP> peel <SEP> (Drosophila) <SEP> homolog <SEP> 2 <SEP> Hs. <SEP> 77256 <tb> Epiderma <SEP>! <SEP> growth <SEP> factor <SEP> Hs. <SEP> 2230 <tb> epidermal <SEP> growth <SEP> factor <SEP> receptor <SEP> (avian <SEP> erythroblastic <SEP> leukemia <SEP> viral <SEP> (v-erb-b) <SEP> oncogene <tb> homolog) <SEP> Hs. <SEP> 77432 <tb> estrogen <SEP> receptor <SEP> 1 <SEP> (alpha) <SEP> Hs.1657 <tb> estrogen <SEP> receptor <SEP> beta <SEP> Hs.103504 <tb> Estrogen <SEP> receptor <SEP> bmdmg <SEP> <SEP> associated site, <SEP> antigen, <SEP> 9 <SEP> Hs. <SEP> 9222 <tb> eukaryotic <SEP> translation <SEP> elongation <SEP> factor <SEP> 1 <SEP> epsilon <SEP> 1 <SEP> Hs. <SEP> 172247 <tb> eukaryotic <SEP> translation <SEP> initiation <SEP> factor <SEP> 3, <SEP> subunit <SEP> 4 <SEP> (delta, <SEP> 44kD) <SEP> Hs. <SEP> 28081 <tb> exportin, <SEP> tRNA <SEP> (nuclear <SEP> export <SEP> receptor <SEP> for <SEP> tRNAs) <SEP> Hs. <SEP> 85951 <tb> fatty acid <SEP> acid <SEP> binding <SEP> protein <SEP> 4, <SEP> adipocyte <SEP> Hs. <SEP> 83213 <tb> fatty <SEP> acid <SEP> binding <SEP> protein <SEP> 7, <SEP> brain <SEP> Hs. <SEP> 26770 <tb> fibroblast <SEP> growth <SEP> factor <SEP> 8 <SEP> Hs. <SEP> 57710 <tb> fibroblast <SEP> growth <SEP> factor <SEP> receptor <SEP> 1 <SEP> (fms-related <SEP> tyrosine <SEP> kinase <SEP> 2, <SEP> Pfeiffer <SEP> syndrome) < SEP> Hs. <SEP> 748 <Tb> <Desc / Clms Page number 54>

<Tb> <tb> flap <SEP> structure-specific <SEP> endonuclease <SEP> 1 <SEP> Hs. <SEP> 4756 <tb> forkhead <SEP> (Drosophi <SEP>! <SEP> a) - <SEP>! <SEP> ike <SEP> 16Hs. <SEP> 239 <tb> four <SEP> and <SEP> has <SEP> half <SEP> <SEP> domains <SEP> I <SEP> Hs. <SEP> 239069 <tb> fragile <SEP> histidine <SEP> triad <SEP> gene <SEP> Hs. <SEP> 77252 <tb> fructose-bis <SEP> host <SEP> hatase <SEP> 1 <SEP> Hs. <SEP> 574 <tb> gamma-glutamyl <SEP> hydrolase <SEP> (conjugase, <SEP> folylpolygammaglutamy <SEP>! <SEP> hydrolase) <SEP> Hs. <SEP> 78619 <tb> gap <SEP> junction SEP> protein <SEP> alpha <SEP> 1, <SEP> 43 <SEP> kD <SEP> or <SEP> connexin <SEP> 43 <SEP> Hs.74471 <tb> GATA-binding <SEQ> protein <SEP> 3 <SEP> Hs.169946 <tb> glutamate <SEP> receptor, <SEQ> ionotropic, <SEP> N-methyl <SEP> D-aspartate <SEP> 2A <SEP> Hs.167464 <tb> glutamate <SEP> receptor, <SEQ> ionotropic, <SEP> N-methyl <SEP> D-aspartate <SEP> 2C <SEP> Hs. <SEP> 36451 <tb> glutathione <SEP> S <SEP> transferase <SEP> pi <SEP> Hs. <SEP> 226795 <tb> glycerol-3-phosphate <SEP> dehydrogenase <SEP> 1 <SEP> (soluble) <SEP> Hs. <SEP> 25478 <tb> granzyme <SEP> A <SEP> (granzyme <SEP> 1, <SEP> cytotoxic <SEP> T-lymphocyte-associated <SEP> serine <SEP> esterase <SEP> 3) <SEP> Hs. <SEP> 90708 <tb> hepatocyte <SEP> nuclear <SEP> factor <SEP> 3, <SEP> alpha <SEP> Hs. <SEP> 105440 <tb> hepsin <SEP> Hs.823 <tb> high <SEP> mobility <SEP> group <SEP> (nonhistone <SEP> chromosomal) <SEP> protein <SEP> isoforms <SEP> I <SEP> and <SEQ> Y <SEP> Hs.139800 <tb> high-mobility <SEP> group <SEP> (nonhistone <SEP> chromosomal) <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 80684 <tb> HIV-1 <SEP> Rev <SEP> binding <SEP> protein <SEP> Hs. <SEP> 171545 <tb> Homo <SEP> sapiens <SEP> ataxia-telangiectasia <SEP> group <SEP> D-associated <SEP> protein <SEP> MRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 82237 <tb> Homo <SEP> sapiens <SEP> clone <SEP> 24703 <SEP> beta-tubulin <SEP> mRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 179661 <Tb> <Desc / Clms Page number 55>

<Tb> <tb> Homo <SEP> sapiens <SEP> HP <SEP> VI <SEP> 6 <SEP> El <SEP> protein <SEP> binding <SEP> protein <SEP> mRNA, <SEP> complete <SEP> cds < SEP> Hs. <SEP> 6566 <tb> Human <SEP> BRCA2 <SEP> region, <SEP> mRNA <SEP> sequence <SEP> CG006H <tb> Human <SEP> breast <SEP> cancer, <SEP> estrogen <SEP> regulated <SEP> LIV-1 <SEP> protein <SEP> (LIV-1) <SEP> mRNA, <SEP> partial <SEP > cds <SEP> Hs. <SEP> 79136 <tb> Human <SEP> cellular <SEP> oncogene <SEP> c-fos <SEP> Hs. <SEP> 25647 <tb> Human <SEP> Ig <SEP> <SEP> chain <SEP> gene <SEP> Hs. <SEP> 76325 <tb> Human <SEP> phosphatidylinositol <SEP> (4,5) <SEP> bisphosphate <SEP> 5-phosphatase <SEP> homolog <SEP> mRNA, <SEP> partial <SEP> cds <SEP> Hs. <SEP> 21492 <tb> Human <SEP> ubiquitin <SEP> carrier <SEP> protein <SEP> (E2-EPF) <SEP> MRNA, <SEP> complete <SEP> cds <SEP> Hs. <SEP> 174070 <tb> hyaluronan-mediated <SEP> motility <SEP> receptor <SEP> (RHAMM) <SEP> Hs. <SEP> 72550 <tb> hydroxyacyl-Coenzyme <SEP> A <SEP> dehydrogenase / 3-ketoacyl-Coenzyme <SEP> A <SEP> thiolse / enoyl-Coenzyme <tb> A <SEP> hydase <SEP> (trifunctional <SEP> protein), <SEP> alpha <SEP> dsubunit <tb> immunoglobulin <SEP> gamma <SEP> 3 <SEP> (Gm <SEP> marker) <SEP> Hs. <SEP> 140 <tb> inhibitor <SEP> of <SEP> growth <SEP> 1 <SEP> Hs.46700 <tb> inhibitor <SEP> of <SEP> growth <SEP> 2 <tb> inositol <SEP> polyphosphate-4-phosphatase, <SEP> type <SEP> II, <SEP> 105kD <SEP> Hs.153687 <tb> insulin-like <SEP> growth <SEP> factor <SEP> 1 <SEP> (somatomedin <SEP> C) <SEP> Hs. <SEP> 85112 <tb> insulin-like <SEP> growth <SEP> factor <SEP> 2 <SEP> (somatomedin <SEP> A) <SEP> Hs. <SEP> 241317 <tb> insulin-like <SEP> growth <SEP> factor <SEP> binding <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 162 <tb> insulin-like <SEP> growth <SEP> factor <SEP> binding <SEP> protein <SEP> 5 <SEP> Hs. <SEP> 102122 <tb> insulin-like <SEP> growth <SEP> factor <SEP> receptor <SEP> 1 <SEP> Hs. <SEP> 239176 <tb> insulin-like <SEP> growth <SEP> factor <SEP> receptor <SEP> 2 <SEP> Hs. <SEP> 76473 <tb> integrin, <SEP> alpha <SEP> 3 <SEP> Hs. <SEP> 265829 <Tb> <Desc / Clms Page number 56>

<Tb> <tb> integrin, <SEP> alpha <SEP> 7 <SEP> Hs.74369 <tb> integrin, <SEP> alpha <SEP> L <SEP> (antigen <SEP> CD11A <SEP> (p180), <SEP> lymphocyte <SEP> function-associated <SEP> antigen <SEP> 1; <SEP > alpha <tb> polypeptide) <SEP> Hs. <SEP> 174103 <tb> integrin, <SEP> beta <SEP> 2 <SEP> (antigen <SEP> CD <SEP> 18 <SEP> (p95), <SEP> lymphocyte <SEP> function-associated <SEP> antigen <SEP> 1 <SEP>; <SEP> macrophage <tb> antigen <SEP> 1 <SEP> (mac-1) <SEP> beta <SEP> subunit) <SEP> Hs. <SEP> 83968 <tb> integrin, <SEP> beta <SEP> 4 <SEP> Hs. <SEP> 85266 <tb> integrin, <SEP> beta <SEP> 8 <SEP> Hs. <SEP> 184908 <tb> intercellular <SEP> adhesion <SEP> molecule <SEP> 2 <SEP> Hs. <SEP> 83733 <tb> interferon <SEP> alpha <SEP> inducible <SEP> protein <SEP> 27 <SEP> Hs.278613 <tb> interferon-induced <SEP> protein <SEP> 17 <SEP> Hs.146360 <tb> interferon-induced, <SEP> hepatitis <SEP> C-associated <SEP> microtubular <SEP> aggregate <SEP> protein <SEP> (44kD) <SEP> Hs. <SEP> 82316 <tb> inter-leuk <SEP> 10 <SEP> receptor, <SEP> alpha <SEP> Hs. <SEP> 327 <tb> interleukin <SEP> 2 <SEP> receptor, <SEP> beta <SEP> Hs. <SEP> 75596 <tb> interleukin <SEP> 3 <SEP> receptor, <SEP> alpha <SEP> (low <SEP> affinity) <SEP> Hs. <SEP> 172689 <tb> kallikrein <SEP> 10 <SEP> Hs. <SEP> 69423 <tb> kallikrein <SEP> 13 <SEP> Hs. <SEP> 165296 <tb> kallikrein <SEP> 3, <SEP> (prostate <SEP> specific <SEP> antigen) <SEP> Hs. <SEP> 171995 <tb> kallikrein <SEP> 6 <SEP> Hs. <SEP> 79361 <tb> kangai <SEP> 1 <SEP> Hs.323946 <tb> keratin <SEP> 17 <SEP> Hs.2785 <tb> keratin <SEP> 18 <SEP> Hs. <SEP> 65114 <tb> keratin <SEP> 19 <SEP> Hs. <SEP> 182265 <Tb> <Desc / Clms Page number 57>

<Tb> <tb> keratin <SEP> 5 <SEP> (epidermolysis <SEP> bullosa <SEP> simplex, <SEP> Dow1-Meara / Kobner / Weber-Cockayne <SEP> types) <SEP> Hs. <SEP> 195850 <tb> keratin <SEP> 7 <SEP> Hs. <SEP> 23881 <tb> keratin <SEP> 8 <SEP> Hs. <SEP> 104624 <tb> KIAA0008 <SEP> gene <SEP> product <SEP> Hs. <SEP> 77695 <tb> KIAA0042 <SEP> gene <SEP> product <SEP> Hs. <SEP> 3104 <tb> KIAA0074 <SEP> protein <SEP> Hs. <SEP> 1192 <tb> KIAA0101 <SEP> gene <SEP> product <SEP> Hs. <SEP> 81892 <tb> KIAA0125 <SEP> gene <SEP> product <SEP> Hs. <SEP> 38365 <tb> KIAA0159 <SEP> gene <SEP> product <SEP> Hs.5719 <tb> KIAA0166 <SEP> gene <SEP> product <SEP> Hs. <SEP> 115778 <tb> KIAA0430 <SEP> gene <SEP> product <SEP> Hs. <SEP> 166163 <tb> KIAA0758 <SEP> protein <SEP> Hs. <SEP> 22039 <tb> KIAA0788 <SEQ> protein <SEP> Hs.181043 <tb> Kiss-1 <SEP> Hs.95008 <tb> lactate <SEP> dehydrogenase <SEP> B <SEP> Hs. <SEP> 234489 <tb> ladinin <SEP> 1 <SEP> Hs. <SEP> 18141 <tb> lamin <SEP> B2 <SEP> Hs. <SEP> 76084 <tb> laminin, <SEP> alpha <SEP> 3 <SEP> (nicein <SEP> (150kD), <SEP> kalinin <SEP> (165kD), <SEP> BM600 <SEP> (150kD), <SEP> epilegrin) <SEP> Hs. <SEP> 83450 <tb> 1aminin, <SEP> gamma <SEP> 2 <SEP> (nicein <SEP> (100kD), <SEP> kalinin <SEP> (105kD), <SEP> BM600 <SEP> (100kD), <SEP> Herlitz <SEP> junctional <tb> epidermolysis <SEP> bullosa)) <SEP> Hs. <SEP> 54451 <tb> LIM <SEP> and <SEP> SH <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 334851 <Tb> <Desc / Clms Page number 58>

<Tb> <tb> LIM <SEP> Binding <SEP> domain <SEP> 2 <SEP> Hs.4980 <tb> LIM <SEP> domain <SEP> only <SEP> 4 <tb> lipocalin <SEP> 1 <SEP> Hs.204238 <tb> lipoprotein <SEP> lipase <SEP> Hs. <SEP> 180878 <tb> LPS-induced <SEP> TNF-alpha <SEP> factor <SEP> Hs. <SEP> 76507 <tb> lumican <SEP> Hs. <SEP> 79914 <tb> lymphocyte-specific <SEP> protein <SEP> tyrosine <SEP> kinase <SEP> Hs. <SEP> 1765 <tb> MAD2 <SEP> (mitotic <SEP> arrest <SEP> deficient, <SEP> yeast, <SEP> homolog) <SEP> -1ike <SEP> 1 <SEP> Hs. <SEP> 79078 <tb> major <SEP> histocompatibility <SEP> complex, <SEP> class <SEP> II, <SEP> DQ <SEP> beta <SEP> 1 <SEP> Hs. <SEP> 73931 <tb> mammaglobin <SEP> 1 <SEP> Hs. <SEP> 46452 <tb> mania <SEP> fringe <SEP> (Drosophila) <SEP> homolog <SEP> Hs. <SEP> 31939 <tb> matrix <SEP> metalloproteinase <SEP> 11 <SEP> (stromelvsin <SEP> 3) <SEP> Hs. <SEP> 155324 <tb> matrix <SEP> metalloproteinase <SEP> 13 <SEP> Hs. <SEP> 2936 <tb> matrix <SEP> metalloproteinase <SEP> 14 <SEP> (membrane-inserted) <SEP> Hs. <SEP> 2399 <tb> matrix <SEP> metalloproteinase <SEP> 17 <SEP> Hs. <SEP> 159581 <tb> matrix <SEP> metalloproteinase <SEP> 9 <SEP>; <SEP> gelatinase <SEP> B <SEP> Hs. <SEP> 151738 <tb> MAX-interacting <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 118630 <tb> Meis <SEP> (mouse) <SEP> peer <SEP> 3 <SEP> Hs. <SEP> 117313 <tb> metastasis <SEP> associated <SEP> 1 <SEP> Hs. <SEP> 101448 <tb> microsomal <SEP> glutathione <SEP> S-transferase <SEP> 1 <SEP> Hs. <SEP> 790 <Tb> <Desc / Clms Page number 59>

<Tb> <tb> minichromosome <SEP> maintenance <SEP> deficient <SEP> (S. <SEP> cerevisiae) <SEP> 2 <SEP> (mitotin) <SEP> Hs. <SEP> 57101 <tb> mucinl <SEP> Hs. <SEP> 89603 <tb> multifunctional <SEP> polypeptide <SEP> similar <SEP> to <SEP> SAICAR <SEP> synthetase <SEP> and <SEP> AIR <SEP> carboxylase <SEP> Hs. <SEP> 117950 <tb> mut <SEP> L <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 1 <SEP> (colon <SEP> cancer, <SEP> nonpolyposis <SEP> type <SEP> 2) <SEP> Hs. <SEP> 57301 <tb> mut <SEP> S <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 3 <SEP> vs. <SEP> 42674 <tb> N-acetyltransferase <SEP> I <SEP> (arylamine <SEP> N-acetyltransferase) <SEP> Hs. <SEP> 155956 <tb> neutrophil <SEP> cytosolic <SEP> factor <SEP> I <SEP> (47kD, <SEQ> chronic <SEP> granulomatous <SEP> disease, <SEP> autosomal <SEP> 1) <SEP> Hs. <SEP> 1583 <tb> N-myc <SEP> downstream <SEP> regulated <SEP> Hs. <SEP> 75789 <tb> non-metastatic <SEP> cells <SEP> 1, <SEQ> protein <SEP> (NM23A) <SEP> expressed <SEP> in <SEP> Hs. <SEP> 118638 <tb> non-POU-domain <SEP> containing, <SEP> octamer <SEP> binding <SEP> Hs. <SEP> 172207 <tb> nuclear <SEP> receptor <SEP> coactivator <SEP> 3 <SEP> Hs. <SEP> 225977 <tb> nuclear <SEP> transcription <SEP> factor, <SEP> Xbox <SEP> binding <SEP> 1 <SEP> Hs. <SEP> 3187 <tb> nucleophosmin <SEP> (nucleolar <SEP> phosphoprotein <SEP> B23, <SEP> numatrin) <SEP> Hs. <SEP> 173205 <tb> osteoblast <SEP> specific <SEP> factor <SEP> 2 <SEP> (fasciclin <SEP> 1-like) <SEP> Hs. <SEP> 136348 <tb> parvalbumin <SEP> Hs. <SEP> 295449 <tb> pescadillo <SEP> (zebrafish) <SEP> homolog <SEP> 1, <SEP> containing <SEP> BRCT <SEP> domainHs. <SEP> 13501 <tb> phosphofructokinase, <SEP> platelet <SEP> Hs. <SEP> 99910 <tb> phospholemman <SEP> Hs. <SEP> 160318 <tb> phospholipase <SEP> A2, <SEP> group <SEP> IIA <SEP> (platelets, <SEP> synovial <SEP> fluid) <SEP> Hs.76422 <tb> phospholipid <SEP> scramblase <SEP> 1 <SEP> Hs.198282 <Tb> <Desc / Clms Page number 60>

<Tb> <tb> pituitary <SEP> tumor-transforming <SEP> 1 <SEP> Hs. <SEP> 181195 <tb> Plakoglobin <SEP> Hs. <SEP> 2340 <tb> plasminogen <SEP> Hs. <SEP> 75576 <tb> plasminogen <SEP> activator <SEP> inhibitor <SEP> 1 <SEP> Hs. <SEP> 82085 <tb> platelet / endothelial <SEP> cell <SEP> adhesion <SEP> molecule <SEP> (CD31 <SEP> antigen) <SEP> Hs. <SEP> 78146 <tb> platelet-derived <SEP> growth <SEP> factor <SEP> receptor, <SEP> beta <SEP> polypeptide <SEP> Hs. <SEP> 76144 <tb> polo <SEP> CDrosophia) <SEP> -1ike <SEP> kinase <SEP> Hs. <SEP> 77597 <tb> polymyositis / scleroderma <SEP> autoantigen <SEP> 1 <SEP> (75kD) <SEP> Hs. <SEP> 91728 <tb> 1 <SEP> Dostmeiotic <SEP> segregation <SEP> increased <SEP> 2-like <SEP> 3 <SEP> Hs. <SEP> 278467 <tb> potassium <SEP> intermediate / small <SEP> conductance <SEP> calcium-activated <SEP> channel, <SE>> subfamily <SEP> N, <SEP> member <SEP> 4 <SEP> Hs. <SEP> 10082 <tb> POU <SEP> domain, <SEP> class <SEP> 2, <SEP> transcription <SEP> factor <SEP> 2 <SEP> Hs. <SEP> 1101 <tb> primase, <SEP> polypeptide <SEP> 1 <SEP> (49kD) <SEP> Hs. <SEP> 82741 <tb> Progesterone <SEP> receptor <SEP> Hs. <SEP> 2905 <tb> prohibitin <SEP> Hs. <SEP> 75323 <tb> prolactin <SEP> Hs. <SEP> 1905 <tb> prolactin-induced <SEP> protein <SEP> Hs. <SEP> 99949 <tb> proliferating <SEP> cell <SEP> nuclear <SEP> antigen <SEP> Hs. <SEP> 78996 <tb> proliferation-associated <SEP> 2G4, <SEP> 38kD <SEP> Hs. <SEP> 5181 <tb> protease <SEP> inhibitor <SEP> 12 <SEP> (neuroserpin) <SEP> Hs. <SEP> 78589 <tb> protease, <SEP> serine, <SEP> 8 <SEP> (prostasin) <SEP> Hs. <SEP> 75799 <Tb> <Desc / Clms Page number 61>

<Tb> <tb> proteasome <SEP> (prosome, <SEP> macropain) <SEP> 26S <SEP> subunit, <SEP> non-ATPase, <SEP> 12 <SEP> Hs. <SEP> 4295 <tb> protein <SEP> phosphatase <SEP> 1, <SEP> catalytic <SEP> subunit, <SEP> beta <SEP> isoform <SEP> Hs. <SEP> 21537 <tb> protein <SEP> tyrosine <SEP> kinase <SEP> 6 <SEP> Hs. <SEP> 51133 <tb> purinergic <SEP> receptor <SEP> P2X, <SEP> ligand-gated <SEP> ion <SEP> channel, <SEP> 4 <SEP> Hs. <SEP> 321709 <tb> RAD51 <SEP> Hs. <SEP> 343807 <tb> RAD54 <SEP> (S. <SEP> cerevisiae) <SEP> -1ike <SEP> Hs. <SEP> 66718 <tb> RAP2A, <SEP> member <SEP> of <SEP> ras <SEP> oncogen <SEP> family <SEP> Hs. <SEP> 301746 <tb> ras <SEP> peer <SEP> gene <SEP> family <SEP> member <SEP> B <SEP> (rhoB) <SEP> Hs. <SEP> 204354 <tb> ras <SEP> peer <SEP> gene <SEP> family, <SEP> member <SEP> H <SEP> Hs. <SEP> 109918 <tb> regulator <SEP> of <SEP> G-protein <SEP> signaling <SEP> 5 <SEP> Hs. <SEP> 24950 <tb> replication <SEP> factor <SEP> C <SEP> (activator <SEP> 1) <SEP> 4 <SEP> (37kD) <SEP> Hs. <SEP> 35120 <tb> RERG <SEP> (ds <SEP> <SEP> EST Collection) <SEP> Hs. <SEP> 21594 <tb> retinoblastoma-like <SEP> 2 <SEP> (fold <SEP> 30) <SEP> Hs. <SEP> 79362 <tb> retinoic <SEP> acid <SEP> receptor <SEP> responder <SEP> (tazarotene <SEP> induced) <SEP> 1 <SEP> Hs. <SEP> 82547 <tb> retinol-binding <SEP> protein <SEP> 4, <SEP> interstitial <SEP> Hs. <SEP> 76461 <tb> ribonucleotide <SEP> reductase <SEP> M1 <SEP> polypeptide <SEP> Hs. <SEP> 2934 <tb> ribosomal <SEP> protein <SEP> L <SEP> 13 <SEP> Hs. <SEP> 180842 <tb> S <SEP> 100 <SEP> calcium <SEP> binding <SEP> pronein <SEP> A4 <SEP> Hs. <SEP> 81256 <tb> S <SEP> 100 <SEP> calcium-binding <SEP> protein <SEP> A2 <SEP> Hs. <SEP> 38991 <tb> S <SEP> 100 <SEP> calcium-binding <SEP> protein <SEP> A <SEP> 8 <SEP> Hs. <SEP> 100000 <Tb> <Desc / Clms Page number 62>

<Tb> <tb> S <SEP> 100 <SEP> calcium-binding <SEP> protein <SEP> A9 <SEP> (calgranulin <SEP> B) <SEP> Hs. <SEP> 112405 <tb> S100 <SEP> calcium-binding <SEP> protein <SEP> P <SEP> Hs.2962 <tb> S100 <SEP> calcium-binding <SEP> protein, <SEP> beta <SEP> (neural) <SEP> Hs.83384 <tb> secreted <SEP> frizzled <SEP> related <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 7306 <tb> secretory <SEP> leukocyte <SEP> protease <SEP> inhibitor <SEP> (antileukoproteinase) <SEP> Hs. <SEP> 251754 <tb> selenium <SEP> binding <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 334841 <tb> SELENOPHOSPHATE <SEP> SYNTHETASE <SEP>; <SEP> Human <SEP> selenium <SEP> donor <SEP> protein <SEP> Hs. <SEP> 118725 <tb> serine <SEP> proteinase <SEP> inhibitor, <SEP> clade <SEP> B, <SEP> member <SEP> 5 <SEP> (maspin) <SEP> Hs. <SEP> 55279 <tb> serine / threonine <SEP> kinase <SEP> 15 <SEP> Hs. <SEP> 48915 <tb> serum <SEP> constitute <SEP> protein <SEP> Hs. <SEP> 148101 <tb> singed <SEP> (Drosophila) -like <SEP> (sea <SEP> urchin <SEP> fascinate <SEP> homolog <SEP> like) <SEP> Hs. <SEP> 118400 <tb> small <SEP> inducible <SEP> cytokine <SEP> subfamily <SEP> A <SEP> (Cys-Cys), <SEP> member <SEP> 18, <SEP> pulmonary <SEP> and <SEP> activationregulated <SEP> Hs. <SEP> 16530 <tb> small <SEP> inducible <SEP> cytokine <SEP> subfamily <SEP> D <SEP> (Cys-X3-Cys), <SEP> member <SEP> 1 <SEP> (fractalkine, <SEP> neurotactin) <SEP> Hs. <SEP> 80420 <tb> small <SEP> nuclear <SEP> ribonucleoprotein <SEP> polypeptide <SEP> B "Hs. <SEP> 82575 <tb> solute <SEP> carrier <SEP> family <SEP> 7 <SEP> (cationic <SEP> amino <SEP> acid <SEP> transporter, <SEP> y + <SEP> System), <SEP> member <SEP > 5 <SEP> Hs. <SEP> 184601 <tb> solute <SEP> carrier <SEP> family <SEP> 9 <SEP> (sodium / hydrogen <SEP> exchanger), <SEP> isoform <SEP> 3 <SEP> regulatory <SEP> factor <SEP> 1 < SEP> Hs. <SEP> 184276 <tb> splicing <SEP> factor, <SEP> arginine / serine-rich <SEP> 5 <SEP> Hs. <SEP> 166975 <tb> stanniocalcin <SEP> 2 <SEP> Hs. <SEP> 155223 <tb> superoxide <SEP> dismutase <SEP> 3, <SEP> extracellular <SEP> Hs. <SEP> 2420 <tb> delete <SEP> oftumorogenicity <SEP> Hs. <SEP> 56937 <Tb> <Desc / Clms Page number 63>

<Tb> <tb> suppression <SEP> of <SEP> tumorogenicity <SEP> Hs. <SEP> 301974 <tb> T-cell <SEP> receptor, <SEP> beta <SEP> cluster <SEP> Hs. <SEP> 2003 <tb> T-cell <SEP> receptor, <SEP> delta <SEP> (V, <SEP> D, <SEP> J, <SEP> C) <SEP> Hs. <SEP> 2014 <tb> TEK <SEP> tyrosine <SEP> kinase, <SEP> endothelial <SEP> (venous <SEP> malformations, <SEP> multiple <SEP> cutaneous <SEP> and <SEP> mucosal) <SEP> Hs. <SEP> 89640 <tb> Telomerase <SEP> reverse <SEP> transcriptase <SEP> Hs. <SEP> 115256 <tb> TGFBl-induced <SEP> anti-apoptotic <SEP> factor <SEP> I <SEP> Hs. <SEP> 75822 <tb> thrombospondin <SEP> 1 <SEP> Hs. <SEP> 87409 <tb> Thy-1 <SEP> cell <SEP> surface <SEP> antigen <SEP> Hs. <SEP> 125359 <tb> thymidylate <SEP> synthetase <SEP> Hs. <SEP> 82962 <tb> tissue <SEP> factor <SEP> pathway <SEP> inhibitor <SEP> (lipoprotein-associated <SEP> coagulation <SEP> inhibitor) <SEP> Hs. <SEP> 170279 <tb> tissue <SEP> inhibitor <SEP> of <SEP> metalloproteinase <SEP> 1 <SEP> (erythroid <SEP> potentiating <SEP> activity, <SEP> collagenase <SEP> inhibitor) <SEP> Hs. <SEP> 5831 <tb> tissue <SEP> inhibitor <SEP> of <SEP> metalloproteinase <SEP> 3 <SEP> Hs. <SEP> 245188 <tb> TNF <SEP> associated <SEP> factor <SEP> 4 <SEP> Hs. <SEP> 8375 <tb> TNF <SEP> receptor-associated <SEP> factor <SEP> 6 <SEP> Hs. <SEP> 90957 <tb> topoisomerase <SEP> (DNA) <SEP> II <SEP> alpha <SEP> (170kD) <SEP> Hs. <SEP> 156346 <tb> topoisomerase <SEP> (DNA) <SEP> II <SEP> beta <SEP> (180kD) <SEP> Hs. <SEP> 75248 <tb> TP53 <SEP> Hs. <SEP> 149923 <tb> transcription <SEP> factor <SEP> AP-2 <SEP> alpha <SEP> (activating <SEP> enhancer-binding <SEP> protein <SEP> 2 <SEP> alpha) <SEP> Hs. <SEP> 18387 <tb> Transforming SEP> growth <SEP> factor, <SEP> alpha <SEP> Hs. <SEP> 170009 <tb> transforming <SEP> growth <SEP> factor, <SEP> beta <SEP> receptor <SEP> III <SEP> (betaglycan, <SEP> 300kD) <SEP> Hs. <SEP> 79059 <Tb> <Desc / Clms Page number 64>

<Tb> <tb> trans1in <SEP> Hs. <SEP> 75066 <tb> Trefoil <SEP> factor <SEP> 1 <SEP> (breast <SEP> cancer, <SEP> estrogen-inducible <SEP> sequence <SEP> expressed <SEP> in) <SEP> Hs. <SEP> 1406 <tb> trophinin-assisting <SEP> protein <SEP> (tastin) <SEP> Hs. <SEP> 171955 <tb> troponin <SEP> I, <SEP> skeletal, <SEP> fast <SEP> Hs. <SEP> 83760 <tb> tryptophany1-tRNA <SEP> synthetase <SEP> Hs. <SEP> 82030 <tb> tyrosine <SEP> kinase <SEP> withimmunoglobulin <SEP> and <SEP> EGF <SEP> homology <SEP> domains <SEP> Hs. <SEP> 78824 <tb> tyrosyl-tRNA <SEP> synthetase <SEP> Hs. <SEP> 239307 <tb> UDP-galactose <SEP> transport <SEP> relatedHs. <SEP> 154073 <tb> UDP-N-acety1-a1pha-D-galactosamine <SEP> 3 <SEP> Hs. <SEP> 278611 <tb> uracil-DNA <SEP> glycosylase <SEP> Hs. <SEP> 78853 <tb> uridine <SEP> monophosphate <SEP> synthetase <SEP> (orotate <SEP> phosphoribosyl <SEP> transferase <SEP> and <SEP> orotidine-5'decarboxylase) <SEP> Hs.2057 <tb> v-erb-b2 <SEP> avian <SEP> erythroblastic <SEP> leukemia <SEP> viral <SEP> oncogene <SEP> homolog <SEP> 2 <SEP> Hs. <SEP> 323910 <tb> very <SEP> low <SEP> density <SEP> lipoprotein <SEP> receptor <SEP> Hs. <SEP> 73729 <tb> v-Ha-ras <SEP> Harvey <SEP> rat <SEP> sarcoma <SEP> viral <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 37003 <tb> vimentin <SEP> Hs. <SEP> 297753 <tb> v-jun <SEP> avian <SEP> sarcoma <SEP> virus <SEP> 17 <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 78465 <tb> v-myb <SEP> avian <SEP> myeloblastosis <SEP> viral <SEP> oncogene <SEP> homolog-like <SEP> 2 <SEP> Hs. <SEP> 179718 <tb> v-myc <SEP> avian <SEP> myelocytomatosis <SEP> viral <SEP> oncogene <SEP> homolog <SEP> Hs. <SEP> 79070 <tb> von <SEP> Willebrand <SEP> factor <SEP> Hs. <SEP> 110802 <tb> WNT1 <SEP> inducible <SEP> signaling <SEP> pathway <SEP> protein <SEP> 2 <SEP> Hs. <SEP> 194679 <Tb> <Desc / Clms Page number 65>

<Tb> <tb> X-box <SEP> binding <SEP> protein <SEP> 1 <SEP> Hs. <SEP> 149923 <tb> Zinc <SEP> fmger <SEP> protein <SEP> 147 <SEP> (estrogen-responsive <SEP> finger <SEP> protein) <SEP> Hs. <SEP> 1579 <tb> zinc <SEP> Finger <SEP> Protein <SEP> 161 <SEP> Hs.167558 <tb> zing <SEP> Finger <SEP> Protein <SEP> 217 <SEP> Hs.155040 <Tb>  27 Application of biochips according to claim 25, in particular in oncology, in particular for breast cancer, in particular to establish a precise and reliable diagnosis. 28 microarrays according to claim 25 characterized in that they comprise the molecular probes listed in Appendix 2 SEQ 2: DNA LESION REPAIR MODULE: 130 PROBES MOLECULAR

<Tb> <tb> Name <SEP> of the <SEP> gene <SEP> Unigene <tb> 8-oxoguanine <SEP> DNA <SEP> glycosylase <SEP> Hs. <SEP> 96398 <tb> ADP-ribosyltransferase <SEP> (NAD +; <SEP> poly <SEP> (ADP-erbose) <SEP> polymerase); <SEP> poly <SEP> (ADP-ribose) <tb> polymerase <SEP> Hs.177766 <tb> ADP-ribosyltransferase <SEP> (NAD + <SEP>; <SEP> poly <SEP> (ADP-ribose) <SEP> polymerase) -like <SEP> 2 <SEP> Hs. <SEP> 24284 <tb> alkylation <SEP> DNA <SEP> repair <SEP> protein <SEP> alkb <SEP> homolog <SEP> Hs. <SEP> 54418 <tb> APEX <SEP> nuclease <SEP> (multifunctional <SEP> DNA <SEP> repair <SEP> enzyme) <SEP>; <SEP> apurinic / apyridinic <SEP> (abasic) <SEP> endonuclease <SEP> Hs. <SEP> 73722 <tb> apurinic / apyrimidinic <SEP> endonuclease <SEP> (APEX <SEP> nuclease) <SEP> -like <SEP> 2 <SEP> protein <SEP> Hs. <SEP> 154149 <tb> ataxia <SEP> telangiectasia <SEP> and <SEP> Rad3 <SEP> related <SEP> Hs. <SEP> 77613 <Tb> <Desc / Clms Page number 66>

<Tb> <tb> ataxia <SEP> telangiectasia <SEP> mutated <SEP> (includes <SEP> complementation <SEP> groups <SEP> A <SEP> C <SEP> and <SEP> D) <SEP> Hs. <SEP> 194382 <tb> ataxia <SEP> telangiectasia <SEP> mutated <SEP> (includes <SEP> complementation <SEP> groups <SEP> A <SEP> C <SEP> and <SEP> D) <SEP> Hs. <SEP> 194382 <tb> Bloom <SEP> syndrome <SEP> Hs. <SEP> 36820 <tb> breast <SEP> cancer <SEP> 1, <SEP> early <SEP> onset <SEP> Hs. <SEP> 194143 <tb> breast <SEP> cancer <SEP> 2, <SEP> early <SEP> onset <SEP> Hs. <SEP> 34012 <tb> caltractin <SEP> (20kD <SEP> calcium-binding <SEP> protein) <SEP>; <SEP> centrin, <SEP> EF-hand <SEP> protein, <SEP> 2Hs. <SEP> 82794 <tb> CHK1 <SEP> (checkpoint, <SE> S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 20295 <tb> CHK2 <SEP> (checkpoint, <SEP> S. <SEP> pombe) <SEP> homologHs. <SEP> 146329 <tb> Cockayne <SEP> syndrome <SEP> 1 <SEP> (classical) <SEP> Hs. <SEP> 32967 <tb> cyclin <SEP> H <SEP> Es. <SEP> 514 <tb> cyclin-dependent <SEP> kinase <SEP> 7 <SEP> (homolog <SEP> of <SEP> Xenopus <SEP> MO <SEP> 15 <SEP> cd-activating <SEP> kinase) <SEP> Hs . <SEP> 184298 <tb> damage-specific <SEP> DNA <SEP> binding <SEQ> protein <SEP> 1 <SEP> (48kD) <SEP> Hs. <SEP> 108327 <tb> damage-specific <SEP> DNA <SEP> binding <SEQ> protein <SEP> 2 <SEP> (48kD) <SEP> Hs. <SEP> 77602 <tb> DMC1 <SEP> Hs. <SEP> 37181 <tb> dUTP <SEP> pyrophosphatase <SEP> Hs. <SEP> 82113 <tb> ESTs / human <SEP> p53 <SEP> R2 <SEP> gene <SEP> for <SEP> ribonucleotide <SEP> reductase <SEP> Hs. <SEP> 94262 <tb> ESTs, <SEP> Weakly <SEP> similar <SEP> to <SEP> DNA <SEP> NUCLEOTIDYLEXOTRANSFERASE <SEP> [H. <SEP> sapiens] / similar <tb> to <SEP> DNA <SEP> polymerase <SEP> <SEP> Hs.46964 <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> complementation <SEP> group <tb> (xeroderma <SEP> pigmentosum <SEP> group <SEP> D <SEP> complementing) <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 1 <tb> (includes <SEP> overlapping <SEP> antisense <SEP> sequence) <SEP> Hs.59544 <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 3 <tb> (xeroderma <SEP> pigmentosum <SEP> group <SEP> B <SEP> complementing) <Tb> <Desc / Clms Page number 67>

<Tb> <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> complementation <SEP> group <SEP> 4 <SEP> Hs. <SEP> 89296 <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 5 <tb> (xeroderma <SEP> pigmentosum, <SEP> supplementation <SEP> group <SEP> G <SEP> (Cockayne <SEP> syndrome)) <tb> excision <SEP> repair <SEP> cross-complementing <SEP> repair <SEP> repair <SEP> deficiency, <SEP> supplementation <SEP> group <SEP> 6 <SEP> Hs.99924 <tb> exonuclease <SEP> 1 <SEP> Hs.47504 <tb> Fanconi <SEP> anemia <SEP> supplementation <SEP> group <SEP> A <SEP> Us. <SEP> 86297 <tb> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> C <SEP> Hs.37953 <tb> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> D1 <tb> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> D2 <SEP> Hs.15607 <tb> Fanconi <SEP> anemia, <SEP> supplementation <SEP> group <SEP> E <SEP> Hs.302003 <tb> Fanconi <SEP> anemia, <SEP> complementation <SEP> group <SEP> F <SEP> Hs. <SEP> 65328 <tb> Fanconi <SEP> Anemia, <SEP> Complementation <SEP> group <SEP> G <SEP> Us. <SEP> 8047 <tb> flap <SEP> structure-specific <SEP> endonuclease <SEP> I <SEP> Hs. <SEP> 4756 <tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 1 <SEP> (62kD <SEP> subunit) <SEP> Hs. <SEP> 89578 <tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 2 <SEP> (30kD <SEP> subunit) <SEP> Hs. <SEP> 191356 <tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 3 <SEP> (34kD <SEP> subunit) <SEP> Hs. <SEP> 90304 <tb> general <SEP> transcription <SEP> factor <SEP> IIH, <SEP> polypeptide <SEP> 4 <SEP> (52kD <SEP> subunit) <SEP> Hs. <SEP> 102910 <tb> H2A <SEP> histone <SEP> family, <SEP> member <SEP> X <SEP> Hs. <SEP> 147097 <tb> HCNP <SEP> rotein <SEP>; <SEP> XPA-bindin <SEP> rotein <SEP> 2 <SEP> Hs. <SEP> 9822 <tb> Homo <SEP> sapiens <SEP> mRNA; <SEP> cDNA <SEP> DKFZjp586G1122 <SEP> (from <SEP> clone <SEP> DKFZp586G1122) <SEP> (MRE11A) <SEP> Hs. <SEP> 20555 <Tb> <Desc / Clms Page number 68>

<Tb> <tb> HUS <SEP> I <SEP> (S. <SEP> pombe) <SEP> checkpoint <SEP> peer <SEP> Hs. <SEP> 152983 <tb> KIAA0086 <SEP> gene <SEP> product <SEP> Hs. <SEP> 1560 <tb> ligase <SEP> 1, <SEP> DNA, <SEP> ATP-dependent <SEP> Hs. <SEP> 1770 <tb> ligase <SEP> III, <SEP> DNA, <SEP> ATP-dependent <SEP> Hs. <SEP> 100299 <tb> ligase <SEP> IV, <SEP> DNA, <SEP> ATP-dependent <SEP> Hs. <SEP> 166091 <tb> household <SEP> a <SEP> three <SEP> 1 <SEP> (CAK <SEP> assembly <SEP> factor <SEP> Hs. <SEP> 32380 <tb> methyl-CpG <SEP> binding <SEP> domain <SEP> protein <SEP> 4 <SEP> Hs. <SEP> 35947 <tb> mitotic <SEP> arrest <SEP> defiance, <SEP> yeast, <SEP> -like2 <SEP> Hs. <SEP> 19400 <tb> MMS19 <SEP> (MET18 <SE> S. <SEP> cerevisiae) - <SEP> like <SEP> Hs. <SEP> 288891 <tb> mutL <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 1 <SEP> (colon <SEP> cancer, <SEP> nonpolyposis <SEP> type <SEP> 2) <SEP> Hs . <SEP> 57301 <tb> mutL <SEP> (E. <SEP> coli) <SEP> homolog3 <SEP> Hs. <SEP> 279842 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 3 <SEP> Hs. <SEP> 42674 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 4 <SEP> Hs. <SEP> 115246 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 5 <SEP> Hs. <SEP> 112193 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 5 <SEP> Hs. <SEP> 112193 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 2 <SEP> Hs. <SEP> 78934 <tb> mutS <SEP> (E. <SEP> coli) <SEP> homolog <SEP> 6 <SEP> Hs. <SEP> 3248 <tb> mutY <SEP> (E. <SEP> coli) <SEP> homolog <SEP> Hs. <SEP> 271353 <tb> Nijmegen <SEP> breakage <SEP> syndrome <SEP> 1 <SEP> (nibrin) <SEP> Hs. <SEP> 25812 <tb> N-methylpurine-DNA <SEP> glycosylase <SEP> Hs. <SEP> 79396 <Tb> <Desc / Clms Page number 69>

<Tb> <tb> nth <SEP> (E. <SEP> coli <SEP> endonuclease <SEP> III <SEP> -1i <SEP> 1 <SEP> Hs. <SEP> 66196 <tb> nudix <SEP> (nucleoside <SEP> diphosphate <SEP> linked <SEP> moiety <SEP> X) -type <SEP> pattern <SEP> 1 <SEP> Hs. <SEP> 388 <tb> O-6-methylguanine-DNA <SEP> methyltransferase <SEP> Hs. <SEP> 1384 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> eta <SEP> Hs. <SEP> 155573 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> gamma <SEP> Hs. <SEP> 80961 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> iota <SEP> Hs. <SEP> 271699 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> kappa <SEP> Us. <SEP> 135756 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> lambda <SEP> Hs. <SEP> 129903 <tb> polymerase <SEP> (DNA <SEP> directed) <SEP> lambda <SEP> Hs. <SEP> 225951 <tb> polymerase <SEP> (DNA <SEP> directed), <SEP> b tas. <SEP> 180107 <tb> polymerase <SEP> (DNA <SEP> directed), <SEP> delta <SEP> 1, <SEP> catalytic <SEP> subunit <SEP> (125kD) <SEP> Hs. <SEP> 99890 <tb> polymerase'DNA <SEP> directed), <SEP> epsilon <SEP> Hs. <SEP> 166846 <tb> polynucleotide <SEP> kinase <SEP> 3'phosphatase <SEP> Hs. <SEP> 78016 <tb> postmeiotic <SEP> segregation <SEP> increased <SEP> (S. <SEP> cerevisiae) <SEP> 1 <SEP> Hs. <SEP> 111749 <tb> postmeiotic <SEP> segregation <SEP> increased <SEP> (S. <SEP> cerevisiae) <SEP> 2 <SEP> Hs. <SEP> 177548 <tb> postmeiotic <SEP> segregation <SEP> increased <SEP> 2-like <SEP> 3 <SEP> Hs. <SEP> 278467 <tb> postmeiotic <SEP> ss <SEP> increased <SEP> 2-like <SEP> 4 <SEP> Hs. <SEP> 278468 <tb> proliferating <SEP> cell <SEP> nuclear <SEP> antigen <SEP> Hs. <SEP> 78996 <tb> protein <SEP> kinase, <SEP> DNA-activated, <SEP> catalytic <SEP> polypeptide <SEP> Hs. <SEP> 155637 <tb> RAD1 <SEP> (S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 7179 <Tb> <Desc / Clms Page number 70>

<Tb> <tb> RAD <SEP> 18 <SEP> Hs. <SEP> 21320 <tb> RAD23 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> A <SEP> Hs. <SEP> 180455 <tb> RAD23 <SEP> (S. <SEP> cerevisiae) <SEP> peer <SEP> B <SEP> Hs. <SEP> 178658 <tb> RAD50 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs. <SEP> 41587 <tb> RAD51 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> (E <SEP> coli <SEP> RecA <SEP> homolog) <SEP> Hs. <SEP> 153667 <tb> RAD51 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> C <SEP> Hs. <SEP> 11393 <tb> RAD51L1Hs. <SEP> 100669 <tb> RAD51 <SEP> Hs. <SEP> 125244 <tb> RAD52 <SEP> (S. <SEP> cerevisiae) <SEP> homolog <SEP> Hs. <SEP> 89571 <tb> RAD54 <SEP> (S. <SEP> cerevisiae) -like <SEP> Hs. <SEP> 66718 <tb> RAD54B <SEP> Hs. <SEP> 128501 <tb> RAD9 <SEP> (S. <SEP> pombe) <SEP> peer <SEP> Hs. <SEP> 240457 <tb> RecQ <SEP> Protein-like <SEP> 4 <SEP> Hs.31442 <tb> replication <SEP> protein <SEP> A1 <SEP> (70kD) <SEP> / <SEP> GS2 <SEP> gene <SEP> (= C9) <SEP> Hs.84318 <tb> replication <SEP> protein <SEP> A2 <SEP> (32kD) <SEP> Hs. <SEP> 79411 <tb> replication <SEP> protein <SEP> A2 <SEP> (32kD) <SEP> Hs. <SEP> 79411 <tb> replication <SEP> protein <SEP> A3 <SEP> (14kD) <SEP> Hs.1608 <tb> REV1 <SEP> (yeast <SEP> hgomolog) - <SEP> like <SEP> Hs.110347 <tb> REV3 <SEP> (yeast <SEP> Homolog) - <SEP> binds, <SEP> catalytic <SEP> subunit <SEP> of <SEP> DNA <SEP> polymerase <SEP> zeta <SEP> Hs. <SEP> 115521 <tb> single-strand <SEP> monofunctional <SEP> uracil <SEP> DNA <SEP> glycosylase <SEP> Hs. <SEP> 5212 <Tb> <Desc / Clms Page number 71>

<Tb> <tb> SP011, <SEP> meiotic <SEP> protein <SEP> covalently <SEP> bound <SEP> to <SEP> DSB <SEP> (S-cerevisiae) -like <SEP> Hs. <SEP> 159737 <tb> three <SEP> time <SEP> repair <SEP> exonuclease <SEP> 1 <SEP> Hs. <SEP> 278408 <tb> three <SEP> time <SEP> repair <SEP> exonuclease <SEP> 2 <SEP> Hs. <SEP> 251398 <tb> thymidine-DNA <SEP> glycosylase <SEP> Hs. <SEP> 173824 <tb> thyroid <SEP> autoantigen <SEP> 70kD <SEP> (Ku <SEP> antigen) <SEP> Hs. <SEP> 197345 <tb> to SEP> oisomerase <SEP> re1ated <SEP> function <SEP> rotein <SEP> 4-2 <SEP> Hs. <SEP> 294030 <tb> tumor <SEP> protein <SEP> 53-binding <SEP> protein, <SEP> 1 <SEP> Hs. <SEP> 170263 <tb> ubiquitin <SEP> activating <SEP> enzyme-2 <SEP> Hs. <SEP> 16695 <tb> ubiquitm-conjugating <SEP> enzyme <SEP> E2A <SEP> (RAD6 <SEP> homolog) <SEP> Hs. <SEP> 80612 <tb> ubiquitin-conjugating <SEP> enzyme <SEP> E2A <SEP> variant <SEP> 2 <SEP> Hs. <SEP> 79300 <tb> ubiquitin-conjugating <SEP> enzyme <SEP> E2N <SEP> (homologous <SEP> to <SEP> yeast <SEP> UBC13) <SEP> Hs. <SEP> 75355 <tb> uracil-DNA <SEP> glycosylase <SEP> Hs. <SEP> 78853 <tb> Wemer <SEP> syndrome <SEP> Hs. <SEP> 150477 <tb> xeroderma <SEP> pigmentosum, <SEP> supplementation <SEP> group <SEP> A <SEP> Hs. <SEP> 192803 <tb> xeroderma <SEP> pigmentosum, <SEP> supplementation <SEP> group <SEP> C <SEP> Hs.320 <tb> X-ray <SEP> <SEP> repair <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 1 <SEP> Hs. <SEP> 98493 <tb> X-ray <SEP> <SEP> repairing <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 2 <SEP> Hs. <SEP> 129727 <tb> X-ray <SEP> <SEP> repair <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 3 <SEP> Hs. <SEP> 99742 <tb> X-ray <SEP> <SEP> repair <SEP> defective <SEP> repair <SEP> in <SEP> Chinese <SEP> hamster <SEP> cells <SEP> 4 <SEP> Hs. <SEP> 150930 <tb> X-ray <SEP> <SEP> repairing <SEP> <SEP> defective <SEP> repair <SEP> in <SEP> China <SEP> hamster <SEP> cells <SEP> 5 <SEP> (double-strand- break <tb> rejoining; <SEP> Ku <SEP> autoantigen, <SEP> 80kD) <SEP> Hs.84981 <Tb> <Desc / Clms Page number 72>  29 Application of biochips according to claim 28 for the assessment of the mechanisms involved and the quality of DNA damage repair, especially in oncology, especially for breast cancer. Application of biochips according to any one of claims 1 to 14,19, and 25,26, and 28, and the method according to any one of claims 15 to 18 and 20 to 24, as diagnostic means in the field of all life sciences, and for any known genome study, for example bovine, plant or bacterial genome; to verify the functionality of a gene in genetically modified organisms; and in virology, biochips are then used to characterize the presence and type of virus infecting an organism. 31 Application according to claim 32 in the medical or veterinary field. 32 Application according to claim 33 in the phytosanitary field.