REVIEW |
Correspondence to: Heinz-Ulrich G. Weier, Dept. of Subcellular Structure, Life Sciences Division, MS 74-157, U. of California, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720. E-mail: ulliweier@hotmail.com
![]() |
Summary |
---|
High-resolution physical maps are indispensable for directed sequencing projects or the finishing stages of shotgun sequencing projects. These maps are also critical for the positional cloning of disease genes and genetic elements that regulate gene expression. Typically, physical maps are based on ordered sets of large insert DNA clones from cosmid, P1/PAC/BAC, or yeast artificial chromosome (YAC) libraries. Recent technical developments provide detailed information about overlaps or gaps between clones and precisely locate the position of sequence tagged sites or expressed sequences, and thus support efforts to determine the complete sequence of the human genome and model organisms. Assembly of physical maps is greatly facilitated by hybridization of non-isotopically labeled DNA probes onto DNA molecules that were released from interphase cell nuclei or recombinant DNA clones, stretched to some extent and then immobilized on a solid support. The bound DNA, collectively called "DNA fibers," may consist of single DNA molecules in some experiments or bundles of chromatin fibers in others. Once released from the interphase nuclei, the DNA fibers become more accessible to probes and detection reagents. Hybridization efficiency is therefore increased, allowing the detection of DNA targets as small as a few hundred base pairs. This review summarizes different approaches to DNA fiber mapping and discusses the detection sensitivity and mapping accuracy as well as recent achievements in mapping expressed sequence tags and DNA replication sites.
(J Histochem Cytochem 49:939948, 2001)
Key Words: physical mapping, DNA fibers, hybridization, FISH, digital image analysis
High-resolution physical maps are indispensable for large-scale, cost-effective gene discovery. The construction of such maps of the human genome and model organisms therefore has been one of the major goals of the human genome project (
High-resolution maps providing ordered sets of cloned DNA fragments at the 100-kb level of resolution are assembled with smaller, more manageable DNA fragments isolated from other libraries. Most groups prefer cloning of genomic DNA in vectors that maintain relatively large DNA fragments without rearrangements, are non-chimeric, and allow easy DNA purification. In general, high-resolution maps are composed of overlapping cosmids (
In early applications of FISH-based clone ordering and assembly of physical maps,
|
The procedure, however, had two obvious problems. Fusion of human sperm with hamster eggs and fixation of pronuclei is a time-consuming, laborious process and might not scale well enough to meet the high-throughput requirements of most genome projects. The second shortfall of the procedure was a complete lack of control over the extent of DNA decondensation and orientation of pronuclei. This spurred efforts in the 1990s to manipulate chromatin or purified DNA molecules that could serve as a template for high-resolution physical mapping of DNA probes. The optimal procedure would be inexpensive, rapid, reproducible, and deliver mapping data limited only by the resolution of the light microscope. A decade later, we find ourselves equipped with an arsenal of complementary FISH-based mapping procedures that cover a very broad range of mapping intervals. Furthermore, the simultaneous development of more sensitive fluorescence detection reagents has pushed the limits of detection down to a few hundred basepairs (bp).
![]() |
DNA Fiber Mapping |
---|
The expression "DNA fiber mapping" has become a collective name for quite different mapping techniques. As indicated in Fig 2, the diameter of DNA fibers increases as DNA molecules with a diameter of 2 nm are packed into chromatin ranging from 10 nm for histone-packed DNA molecules and 30 nm for chromatin fibers all the way to chromatids of 700 nm diameter. Chromatin can be released from interphase cell nuclei by various chemical or mechanical methods, and investigators tried to coin names that reflect their individual approach. Isolation of DNA from cell nuclei, extension, and preparation of chromatin or DNA fibers with diameters ranging in size from a few to several hundred nm (Fig 2) improves the accessibility of the DNA targets for both probes and detection reagents. Accordingly, the hybridization efficiencies increase, and DNA targets of less than 1 kb can be detected routinely using procedures normally applied in metaphase and interphase cell FISH.
|
In 1992, Heng et al. described the use of chemicals to release chromatin from interphase cell nuclei. The results look somewhat similar to the propidium iodide-stained free chromatin shown in Fig 1C.
-satellite DNA arrays or single-copy DNA could typically be derived from analysis of only 510 cells. These findings were confirmed independently by the work of
If DNA molecules could be stretched uniformly in one direction, they might provide linear templates for visual FISH mapping.
In the following year,
Procedures published by 1995 allowed FISH for most preparations of decondensed nuclear or isolated cloned DNA and visualization of probe overlap to provide some information about the existence and size of gaps between clones (
We demonstrated that cloned DNA fragments can readily be mapped by FISH onto DNA molecules straightened by the hydrodynamic action of a receding meniscus and, referring to its quantitative nature, we termed our technique "Quantitative DNA Fiber Mapping (QDFM)" (2.3 kb/µm, i.e., approximately 30% over the length predicted for a double-stranded DNA molecule of the same size (
The subsequent studies of DNA molecules by atomic force microscopy,
![]() |
Overcoming Challenges in Mapping Tandemly Repeated DNA Sequences |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Most mammalian genomes contain very large blocks of heterochromatin. Certain regions such as the (near)-centromeric heterochromatin seem to be involved in karyokinesis and chromosome association during meiosis (
Several groups applied DNA fiber mapping techniques to investigate the interface between euchromatic and heterochromatic regions as well as the organization of tandem DNA repeats in humans (
![]() |
Mapping of Single-copy DNA |
---|
Physical Map Assembly
The assembly of high-resolution physical maps has been a major application of DNA fiber mapping. Successful efforts to construct local maps for delineation of disease genes were mentioned above, but the success of additional investigators deserves proper recognition.
![]() |
Direct Visualization of Gene Amplifications and Deletions |
---|
Linearly extended chromatin or DNA molecules are ideal substrates to study gene amplification or deletions.
![]() |
Mapping of Expressed Sequences |
---|
Applications of DNA fiber mapping extend beyond map assembly and can provide valuable information for clone validation, definition of a minimal tiling path, and quality control in the sequence assembly process. Even more exciting, its high hybridization efficiency makes DNA fiber mapping the method of choice for visual mapping of expressed sequences.
Several approaches exist to map expressed sequences or to study the organization of larger genes. Gene fragments or entire cDNAs cloned in plasmid vectors can be amplified by in vitro DNA amplification using the polymerase chain reaction (PCR), labeled with reporter molecules, and used as hybridization probes (
The organization of genes in transcribed sequences interrupted by intronic sequences can be easily demonstrated by DNA fiberFISH. We used QDFM in an attempt to resolve the structure of a gene from chromosome 20 frequently found amplified in human tumors (
Technical developments in recent years have opened the doors to mapping of even smaller exons. In 1996, Florijn et al. demonstrated the use of DNA halo preps for mapping of exons ranging in size from 202 to 778 bp. Co-hybridization of co-linear cosmid clones enabled this group to reproducibly locate exon fragments of about 200 bp on extended genomic DNA in the context of the cognate cosmid signal. Detection efficiencies of 7090% were found with probes larger than 400 bp, but the detection efficiency decreased to about 30% when fragments of about 200250 bp were mapped.
More recently, Aaltonen and co-workers (1997;
In the experiments conducted by
![]() |
High-resolution Studies of DNA Replication |
---|
Despite intense efforts, the orderly activation of replication sites in genomes of higher organisms remains largely unexplained. The main reason for this may be the complexity of a process orchestrating the partly parallel activation of an estimated 104 to 106 replication sites.
DNA fiber mapping, with its high resolution and sensitivity, might provide important mapping information about the location and spacing of replication sites. Several groups used fiber mapping techniques to demonstrate replication forks in yeast (
Studies described by -satellite DNA arrays by incorporation of BrdU into newly synthesized DNA, followed by hybridization of biotinylated chromosome-specific alphoid probes to DNA released from fibroblast or lymphoblast cell nuclei. Using the DNA halo preparations, he was able to demonstrate many independent replication sites within the large clusters of tandemly repeated alphoid DNA and partially hemizygous hybridization patterns in support of the hypothesis that replication of
-satellite DNA on homologous chromosomes is highly asynchronous.
The recent work of
![]() |
Conclusions |
---|
Recent research has lead to major improvements in hybridization-based physical mapping procedures. Developments in DNA fiber mapping have reached the point of immediate practical utility: DNA probes as small as 500 bp can be mapped routinely onto immobilized templates composed of linear or circular DNA molecules that range in size from less than 10 kb to more than one Mbp. Uniform stretching facilitates the conversion of measured physical distances into genomic distances. The highly reproducible stretching procedures require analysis of only a few DNA molecules for accurate determination of map positions by multicolor fluorescence microscopy and digital image analysis. A mapping accuracy in the kb range coupled to efficient signal amplification procedures to visualize signals from small targets allows rapid assembly of high-resolution physical maps for large-scale sequencing and map closure as well as high-resolution maps of expressed sequences.
DNA fiber mapping technologies will enhance performance of virtually all mapping and sequencing projects, including ongoing and future sequencing of model organisms and bacterial genomes. Implementation of these technologies will expedite sequencing by increasing parallelism, will lower the overall cost by reducing template redundancies, and will expedite map closure. Furthermore, the techniques will benefit the positional cloning of disease genes and characterization of genomic elements controlling their expression.
![]() |
Acknowledgments |
---|
Supported by a grant from the Director, Office of Science, Office of Biological and Environmental Research, US Department of Energy, under Contract DE-AC03-76SF00098, by the "Training Program in Genome Research" sponsored by the University of California Systemwide Biotechnology Research and Education Program (#S96-03), and by a grant from the Breast Cancer Research Program, US Army Medical Research and Materiel Command, United States, Department of the Army (BC98-0937).
Received for publication November 15, 2000; accepted March 26, 2001.
![]() |
Literature Cited |
---|
Aaltonen J, HorelliKuitunen N, Fan JB, Bjorses P, Perheentupa J, Myers R, Palotie A, Peltonen L (1997) High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH. Genome Res 7:820-829
Aburatani H, Stanton VP, Housman DE (1996) High-resolution physical mapping by combined Alu-hybridization/PCR screening: construction of a yeast artificial chromosome map covering 31 centimorgans in 3p21-p14. Proc Natl Acad Sci USA 93:4474-4479
Ashworth LK, Batzer MA, Brandriff B, Branscomb E, de Jong P, Garcia E, Garnes JA, Gordon LA, Lamerdin JE, Lennon G, Mohrenweiser H, Olsen AS, Slezak T, Carrano AV (1995) An integrated metric physical map of human chromosome 19. Nature Genet 11:422-427[Medline]
Bell C, Budarf ML, Nieuwenhuijsen BW, Barnoski BL, Buetow KH (1995) Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers. Hum Mol Genet 4:59-69[Abstract]
BellannéChantelot C, Lacroix B, Ougen P, Billault A, Beaufils S, Bertrand S, Georges I, Glibert F, Gros I, Lucotte G, Susini L, Codani JJ, Gesnouin P, Pook S, Vaysseix G, Lu-Kuo J, Ried T, Ward D, Chumakov I, Le Paslier D, Barillot E, Cohen D (1992) Mapping the whole human genome by fingerprinting yeast artificial chromosomes. Cell 70:1059-1068[Medline]
Bensimon A, Simon A, Chiffaudel A, Croquette V, Heslot F, Bensimon D (1994) Alignment and sensitive detection of DNA by a moving interface. Science 265:2096-2098[Medline]
Brandriff B, Gordon L, Trask B (1991a) A new system for high-resolution DNA sequence mapping interphase pronuclei. Genomics 10:75-82[Medline]
Brandriff BF, Gordon LA, Trask BJ (1991b) DNA sequence mapping by fluorescence in situ hybridization. Environ Mol Mutagen 18:259-262[Medline]
Brandriff BF, Gordon LA, Tynan KT, Olsen AS, Mohrenweiser HW, Fertitta A, Carrano AV, Trask BJ (1992) Order and genomic distances among members of the carcinoembryonic antigen (CEA) gene family determined by fluorescence in situ hybridization. Genomics 12:773-779[Medline]
Branscomb E, Slezak T, Pae R, Galas D, Carrano AV, Waterman M (1990) Optimizing restriction fragment fingerprinting methods for ordering large genomic libraries. Genomics 8:351-366[Medline]
Cheng J-F, Weier H-UG (1997) Approaches to high resolution physical mapping of the human genome. In Fox CF, Connor TH, eds. Biotechnology International. San Francisco, Universal Medical Press, 149-157
Coffey AJ, Roberts RG, Green ED, Cole CG, Butler R, Anand R, Giannelli F, Bentley DR (1992) Construction of a 2.6-Mb contig in yeast artificial chromosomes spanning the human dystrophin gene using an STS-based approach. Genomics 12:474-484[Medline]
Cohen D, Chumakov I, Weissenbach J (1993) A first-generation physical map of the human genome. Nature 366:698-701[Medline]
Collins F, Galas D (1993) A new five-year plan for the U.S. human genome project. Science 262:43-46[Medline]
Cook PR, Brazell IA, Jost E (1976) Characterization of nuclear structures containing superhelical DNA. J Cell Sci 22:303-324[Abstract]
Cox DR, Burmeister M, Price ER, Kim S, Myers RM (1990) Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250:245-250[Medline]
Dozortsev D, Coleman A, Nagy P, Diamond MP, Ermilov A, Weier U, Liyanage M, Ried T (2000) Nucleoli in a pronuclei-stage mouse embryo are represented by major satellite DNA of interconnecting chromosomes. Fertil Steril 73:366-371[Medline]
Duell T, Nielsen LB, Jones A, Young SG, Weier H-UG (1998) Construction of two near-kilobase resolution restriction maps of the 5' regulatory region of the human apolipoprotein B gene by quantitative DNA fiber mapping (QDFM). Cytogenet Cell Genet 79:64-70
Duell T, Wang M, Wu J, Kim U-J, Weier H-UG (1997) High resolution physical map of the immunoglobulin lambda variant gene cluster assembled by quantitative DNA fiber mapping. Genomics 45:479-486[Medline]
Epplen JT, Maueler W, Santos EJ (1998) On GATAGATA and other "junk" in the barren stretch of genomic desert. Cytogenet Cell Genet 80:75-82[Medline]
Fidlerova H, Senger G, Kost M, Sanseau P, Sheer D (1994) Two simple procedures for releasing chromatin from routinely fixed cells for fluorescence in situ hybridization. Cytogenet Cell Genet 65:203-205[Medline]
Florijn RJ, Bonden LAJ, Vrolijk H, Wiegant J, Vaandrager J-W, Baas F, den Dunnen JT, Tanke HJ, van Ommen G-JB, Raap AK (1995) High-resolution DNA fiber-FISH for genomic DNA mapping and colour bar-coding of large genes. Hum Mol Genet 4:831-836[Abstract]
Florijn RJ, van der Rijke FM, Vrolijk H, Blonden LA, Hofker MH, den Dunnen JT, Tanke HJ, van Ommen GJ, Raap AK (1996) Exon mapping by fiber-FISH or LR-PCR. Genomics 38:277-282[Medline]
Fransz PF, AlonsoBlanco C, Liharska TB, Peeters AJM, Zabel P, de Jong JH (1996) High-resolution physical mapping in Arabidopsis thaliana and tomato by fluorescence in situ hybridization to extended DNA fibres. Plant J 9:421-430[Medline]
Gerdes MG, Carter KC, Moen PT, Jr, Lawrence JB (1994) Dynamic changes in the higher-level chromatin organization of specific sequences revealed by in situ hybridization to nuclear halos. J Cell Biol 126:289-304[Abstract]
Green ED, Mohr RM, Idol JR, Jones M, Buckingham JM, Deaven LL, Moyzis RK, Olson MV (1991) Systematic generation of sequence-tagged sites for physical mapping of human chromosomes application to the mapping of human chromosome 7 using yeast artificial chromosomes. Genomics 11:548-564[Medline]
Green ED, Olson MV (1990) Systematic screening of yeast artificial-chromosome libraries by use of the polymerase chain reaction. Proc Natl Acad Sci USA 87:1213-1217[Abstract]
Haaf T (1996) High-resolution analysis of DNA replication in released chromatin fibers containing 5-bromodeoxyuridine. Biotechniques 21:1050-1054[Medline]
Haaf T, Ward DC (1994a) High resolution ordering of YAC contigs using extended chromatin and chromosomes. Hum Mol Genet 3:629-633[Abstract]
Haaf T, Ward DC (1994b) Structural analysis of -satellite DNA centromere proteins using extended chromatin and chromosomes. Hum Mol Genet 3:697-709[Abstract]
Heiskanen M, Hellsten E, Kallioniemi OP, Makela TP, Alitalo K, Peltonen L, Palotie A (1995) Visual mapping by fiber-FISH. Genomics 30:31-36[Medline]
Heiskanen M, Kallioniemi O, Palotie A (1996) Fiber-FISH: experiences and a refined protocol. Genet Anal Biomol Eng 12:179-184
Heiskanen M, Karhu R, Hellsten E, Peltonen L, Kallioniemi OP, Palotie A (1994) High resolution mapping using fluorescence in situ hybridization to extended DNA fibers prepared from agarose-embedded cells. Biotechniques 17:928-933[Medline]
Heng HHQ, Squire J, Tsui LC (1992) High-resolution mapping of mammalian genes by in situ hybridization to free chromatin. Proc Natl Acad Sci USA 89:9509-9513[Abstract]
Herrick J, Stanislawski P, Hyrien O, Bensimon A (2000) Replication fork density increases during DNA synthesis in X. laevis egg extracts. J Mol Biol 300:1133-1142[Medline]
Hoheisel JD, Lehrach H (1993) Use of reference libraries and hybridisation fingerprinting for relational genome analysis. FEBS Lett 325:118-122[Medline]
HorelliKuitunen N, Aaltonen J, Yaspo ML, Eeva M, Wessman M, Peltonen L, Palotie A (1999) Mapping ESTs by fiber-FISH. Genome Res 9:62-71
Hu J, Wang M, Weier HUG, Frantz P, Kolbe W, Olgletree DF, Salmeron M (1996) Imaging of single extended DNA molecules on flat (aminopropyl)triethoxysilane-mica by atomic force microscopy. Langmuir 12:1697-1700
Hyrien O, Mechali M (1992) Plasmid replication in xenopus eggs and egg extracts: a 2d gel electrophoretic analysis. Nucleic Acids Res 20:1463-1469[Abstract]
Ioannou PA, Amemiya CT, Garnes J, Kroisel PM, Shizuya H, Chen C, Batzer M, De Jong PJ (1994) A new bacteriophage P1-derived vector for the propagation of large human DNA fragments. Nature Genet 6:84-89[Medline]
Jackson SA, Dong F, Jiang J (1999) Digital mapping of bacterial artificial chromosomes by fluorescence in situ hybridization. Plant J 17:581-587[Medline]
Jackson SA, Wang ML, Goodman HM, Jiang J (1998) Application of fiber-FISH in physical mapping of Arabidopsis thaliana. Genome 41:566-572[Medline]
Klockars T, Savukoski M, Isosomppi J, Laan M, Jarvela I, Petrukhin K, Palotie A, Peltonen L (1996) Efficient construction of a physical map by fiber-FISH of the CLN5 region: refined assignment and long-range contig covering the critical region on 13q22. Genomics 35:71-78[Medline]
Lawrence JB, Carter KC, Gerdes MJ (1992) Extending the capabilities of interphase chromatin mapping. Nature Genet 2:171-172[Medline]
Li Y, Lee C, Hsu TH, Li SY, Lin CC (2000) Direct visualization of the genomic distribution and organization of two cervid centromeric satellite DNA families. Cytogenet Cell Genet 89:192-198[Medline]
Locke J, Rairdan G, McDermid H, Nash D, Pilgrim D, Bell J, Roy K, Hodgetts R (1996) Cross-screening: A new method to assemble clones rapidly and unambiguously into contigs. Genome Res 6:155-165[Abstract]
Lu-Kuo JM, Le Paslier D, Weissenbach J, Chumakov I, Cohen D, Ward DC (1994) Construction of a YAC contig and a STS map spanning at least seven megabasepairs in chromosome 5q34-35. Hum Mol Genet 3:99-106[Abstract]
Michalet X, Ekong R, Fougerousse F, Rousseaux S, Schurra C, Hornigold N, van Slegtenhorst M, Wolfe J, Povey S, Beckmann JS, Bensimon A (1997) Dynamic molecular combing: Stretching the whole human genome for high-resolution studies. Science 277:1518-1523
Nelson DL (1991) Applications of polymerase chain reaction methods in genome mapping. Curr Opin Genet Dev 1:62-68[Medline]
Nizetic D, Gellen L, Hamvas RM, Mott R, Grigoriev A, Vatcheva R, Zehetner G, Yaspo ML, Dutriaux A, Lopes C, Delabar JM, Van Broeckhoven C, Potier MC, Lehrach H (1994) An integrated YAC-overlap and cosmid-pocket map of the human chromosome 21. Hum Mol Genet 3:759-770[Abstract]
Olson MV (1993) The human genome project. Proc Natl Acad Sci USA 90:4338-4344[Abstract]
Parra I, Windle B (1993) High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genet 5:17-21[Medline]
Patil N, Peterson A, Rothman A, DeJong PJ, Myers RM, Cox DR (1994) A high resolution physical map of 2.5 Mbp of the Down syndrome region on chromosome 21. Hum Mol Genet 3:1811-1817[Abstract]
Peters LL, Weier HU, Walensky LD, Snyder SH, Parra M, Mohandas N, Conboy JG (1998) Four paralogous protein 4.1 genes map to distinct chromosomes in mouse and human. Genomics 54:348-350[Medline]
Pierce JC, Sauer B, Sternberg N (1992) A positive selection vector for cloning high molecular weight DNA by the bacteriophage-P1 systemimproved cloning efficacy. Proc Natl Acad Sci USA 89:2056-2060[Abstract]
Raap AK, van de Corput MP, Vervenne RA, van Gijlswijk RP, Tanke HJ, Wiegant J (1995) Ultra-sensitive FISH using peroxidase-mediated deposition of biotin- or fluorochrome tyramides. Hum Mol Genet 4:529-534[Abstract]
Rosenberg C, Florijn RJ, Van der Rijke FM, Blonden LA, Raap TK, Van Ommen GJ, den Dunnen JT (1995) High resolution DNA fiber-FISH on yeast artificial chromosomes: direct visualization of DNA replication. Nature Genet 10:477-479[Medline]
Sapolsky RJ, Lipshutz RJ (1996) Mapping genomic library clones using oligonucleotide arrays. Genomics 33:445-456[Medline]
Selleri L, Eubanks JH, Giovannini M, Hermanson GG, Romo A, Djabali M, Maurer S, McElligott DL, Smith MW, Evans GA (1992) Detection and characterization of "chimeric" yeast artificial chromosome clones by fluorescent in situ suppression hybridization. Genomics 14:536-541[Medline]
Senger G, Jones TA, Fidlerova H, Sanseau P, Trowsdale J, Duff M, Sheer D (1994) Released chromatin: linearized DNA for high resolution fluorescence in situ hybridization. Hum Mol Genet 3:1275-1280[Abstract]
Shiels C, Coutelle C, Huxley C (1997) Analysis of ribosomal and alphoid repetitive DNA by fiber-FISH. Cytogenet Cell Genet 76:20-22[Medline]
Shizuya H, Birren B, Kim UJ, Mancino V, Slepak T, Tachiiri Y, Simon M (1992) Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector. Proc Natl Acad Sci USA 89:8794-8797[Abstract]
Sjöberg A, Peelman LJ, Chowdhary BP (1997) Application of three different methods to analyse fibre-fish results obtained using four lambda clones from the porcine MHC III region. Chromosome Res 5:247-253[Medline]
Stallings RL, Doggett NA, Callen D, Apostolou S, Chen LZ, Nancarrow JK, Whitmore SA, Harris P, Michison H, Breuning M, Saris JJ, Fickett J, Cinkosky M, Torney DC, Hildebrand CE, Moyzis RK (1992) Evaluation of a cosmid contig physical map of human chromosome 16. Genomics 13:1031-1039[Medline]
Tanner M, Tirkkonon A, Kallioniemi A, Collins C, Stokke T, Karhu R, Kowbel D, Shadravan F, Hintz M, Kuo W-L, Waldman F, Isola J, Gray JW, Kallioniemi O-P (1994) Increased copy number at 20q13 in breast cancer defining the critical region: exclusion of candidate genes. Cancer Res 54:4257-4260[Abstract]
Theuns J, Cruts M, Del-Favero J, Goossens D, Dauwerse H, Wehnert A, den Dunnen JT, Van Broeckhoven C (1999) Determination of the genomic organization of human presenilin 1 by fiber-fish analysis and restriction mapping of cloned DNA. Mammal Genome 10:410-414[Medline]
Trask B, Pinkel D, van den Engh G (1989) The proximity of DNA sequences in interphase cell nuclei is correlated to genomic distance and permits ordering of cosmids spanning 250 kilobase pairs. Genomics 5:710-717[Medline]
Tynan K, Olsen A, Trask B, de Jong P, Thompson J, Zimmermann W, Carrano A, Mohrenweiser H (1992) Assembly and analysis of cosmid contigs in the CEA-gene family region of human chromosome 19. Nucleic Acids Res 20:1629-1636[Abstract]
van der Rijke FM, Florijn RJ, Tanke HJ, Raap AK (2000) DNA fiber-FISH staining mechanism. J Histochem Cytochem 48:743-745
Vetrie D, Bobrow M, Harris A (1993) Construction of a 5.2-megabase physical map of the human X chromosome at Xq22 using pulsed-field gel electrophoresis and yeast artificial chromosomes. Genomics 15:631-642[Medline]
Vogelstein B, Pardoll DM, Coffey DS (1980) Supercoiled loops and eucaryotic DNA replication. Cell 22:79-85[Medline]
Wang M, Duell T, Gray JW, Weier H-UG (1996) High sensitivity, high resolution physical mapping by fluorescence in situ hybridization on to individual straightened DNA molecules. Bioimaging 4:1-11
Waterston R, Sulston J (1995) The genome of Caenorhabditis elegans. Proc Natl Acad Sci USA 92:10836-10840[Abstract]
Weier H-UG (2001) Quantitative DNA Fiber Mapping. In Darzynkiewicz Z, Chrissman HA, Robinson JP, eds. Methods in Cell Biology. Vol 64. Part B. San Diego, Academic Press, 33-53
Weier H-UG, Wang M, Mullikin JC, Zhu Y, Cheng J-F, Greulich KM, Bensimon A, Gray JW (1995) Quantitative DNA fiber mapping. Hum Mol Genet 4:1903-1910[Abstract]
Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M (1992) A second-generation linkage map of the human genome. Nature 359:794-801[Medline]
Wiegant J, Kalle W, Mullenders L, Brookes S, Hoovers JM, Dauwerse JG, van Ommen GJ, Raap AK (1992) High-resolution in situ hybridization using DNA halo preparations. Hum Mol Genet 1:587-591[Abstract]
Yokota H, Johnson F, Lu H, Robinson RM, Belu AM, Garrison MD, Ratner BD, Trask BJ, Miller DL (1997) A new method for straightening DNA molecules for optical restriction mapping. Nucleic Acids Res 25:1064-1070
Zhong XB, Fransz PF, WennekesEden J, Ramanna MS, van Kammen A, Zabel P, Hans de Jong J (1998) FISH studies reveal the molecular and chromosomal organization of individual telomere domains in tomato. Plant J 13:507-517[Medline]
Zucchi I, Schlessinger D (1992) Distribution of moderately repetitive sequences pTR5 and LF1 in Xq24-q28 human DNA and their use in assembling YAC contigs. Genomics 12:264-275[Medline]