[Body surface isopotential mapping of ventricular extrasystole, with special reference to the QRS mapping during ventricular pacing].
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Retinoic acid (RA) activated the extracellular signal-regulated kinase (ERK) 2 mitogen-activated protein kinase (MAPK) of HL-60 human myeloblastic leukemia cells before causing myeloid differentiation and cell cycle arrest associated with hypophosphorylation of the retinoblastoma (RB) tumor suppressor protein. ERK2 activation by mitogen-activated protein/ERK kinase (MEK) was necessary for RA-induced differentiation in studies using PD98059 to block MEK phosphorylation. G0 growth arrest and RB tumor suppressor protein hypophosphorylation (which is typically associated with induced differentiation and G0 arrest), two putatively RB-regulated processes, also depended on ERK2 activation by MEK. Activation of ERK2 by RA occurred within hours and persisted until the onset of RB hypophosphorylation, differentiation, and arrest. ERK2 activation was probably needed early, because delaying the addition of PD98059 relative to that of RA restored most of the RA-induced cellular response. In contrast to RA (which activates RA receptors (RARs) and retinoid X receptors in HL-60 cells with its metabolite retinoids), a retinoid that selectively binds RAR-gamma, which is not expressed in HL-60 cells, was relatively ineffective in causing ERK2 activation. This is consistent with the need for a nuclear retinoid receptor function in RA-induced ERK2 activation. RA reduced the amount of unphosphorylated RAR-alpha, whose activation is necessary for RA-induced differentiation and arrest. This shifted the ratio of phosphorylated:unphosphorylated RAR-alpha to predominantly the phosphorylated form. Unlike other steroid thyroid hormone receptors susceptible to phosphorylation and activation by MAPKs, RAR-alpha was not phosphorylated by the activated ERK2 MAPK. The results thus show that RA augments MEK-dependent ERK2 activation that is needed for subsequent RB hypophosphorylation, cell differentiation, and G0 arrest. The process seems to be nuclear receptor dependent and an early seminal component of RA signaling causing differentiation and growth arrest.
This paper describes a fast and scalable strategy for constructing a radiation hybrid (RH) map from data on different RH panels. The maps on each panel are then integrated to produce a single RH map for the genome. Recurring problems in using maps from several sources are that the maps use different markers, the maps do not place the overlapping markers in same order, and the objective functions for map quality are incomparable. We use methods from combinatorial optimization to develop a strategy that addresses these issues. We show that by the standard objective functions of obligate chromosome breaks and maximum likelihood, software for the traveling salesman problem produces RH maps with better quality much more quickly than using software specifically tailored for RH mapping. We use known algorithms for the longest common subsequence problem as part of our map integration strategy. We demonstrate our methods by reconstructing and integrating maps for markers typed on the Genebridge 4 (GB4) and the Stanford G3 panels publicly available from the RH database. We compare map quality of our integrated map with published maps for GB4 panel and G3 panel by considering whether markers occur in the same order on a map and in DNA sequence contigs submitted to GenBank. We find that all of the maps are inconsistent with the sequence data for at least 50% of the contigs, but our integrated maps are more consistent. The map integration strategy not only scales to multiple RH maps but also to any maps that have comparable criteria for measuring map quality. Our software improves on current technology for doing RH mapping in areas of computation time and algorithms for considering a large number of markers for mapping. The essential impediments to producing dense high-quality RH maps are data quality and panel size, not computation.
We prepared a monoclonal antibody to microtubule-associated protein 1 (MAP 1), one of the two major high molecular weight MAP found in microtubules isolated from brain tissue. We found that MAP 1 can be resolved by SDS PAGE into three electrophoretic bands, which we have designated MAP 1A, MAP 1B, and MAP 1C in order of increasing electrophoretic mobility. Our antibody recognized exclusively MAP 1A, the most abundant and largest MAP 1 polypeptide. To determine the distribution of MAP 1A in nervous system tissues and cells, we examined tissue sections from rat brain and spinal cord, as well as primary cultures of newborn rat brain by immunofluorescence microscopy. Anti-MAP 1A stained white matter and gray matter regions, while a polyclonal anti-MAP 2 antibody previously prepared in this laboratory stained only gray matter. This confirmed our earlier biochemical results, which indicated that MAP 1 is more uniformly distributed in brain tissue than MAP 2 (Vallee, R.B., 1982, J. Cell Biol., 92:435-442). To determine the identity of cells and cellular processes immunoreactive with anti-MAP 1A, we examined a variety of brain and spinal cord regions. Fibrous staining of white matter by anti-MAP 1A was generally observed. This was due in part to immunoreactivity of axons, as judged by examination of axonal fiber tracts in the cerebral cortex and of large myelinated axons in the spinal cord and in spinal nerve roots. Cells with the morphology of oligodendrocytes were brightly labeled in white matter. Intense staining of Purkinje cell dendrites in the cerebellar cortex and of the apical dendrites of pyramidal cells in the cerebral cortex was observed. By double-labeling with antibodies to MAP 1A and MAP 2, the presence of both MAP in identical dendrites and neuronal perikarya was found. In primary brain cell cultures anti-MAP 2 stained predominantly cells of neuronal morphology. In contrast, anti-MAP 1A stained nearly all cells. Included among these were neurons, oligodendrocytes and astrocytes as determined by double-labeling with anti-MAP 1A in combination with antibody to MAP 2, myelin basic protein or glial fibrillary acidic protein, respectively. These results indicate that in contrast to MAP 2, which is specifically enriched in dendrites and perikarya of neurons, MAP 1A is widely distributed in the nervous system.
BACKGROUND: Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6x coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. RESULTS: An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6x bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. CONCLUSION: Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6x sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.
The major high molecular weight microtubule-associated polypeptides from hog brain (MAP-1 and MAP-2) were compared by one- and two-dimensional peptide mapping under varied conditions and by immunological techniques. Partial digestion of MAP-1 and MAP-2 with Staphylococcus aureus V8 protease and analysis in one dimension gave rise to very similar peptide maps independent of whether 125I-, 3H-, or 32P-labeled proteins were used. One-dimensional cleavage patterns of significant similarity were also obtained by partial digestion of MAP-1 and MAP-2 using trypsin or chymotrypsin. Furthermore, a pronounced similarity, although clear nonidentity, of MAP-1 and MAP-2 was also revealed after exhaustive digestion of 125I-labeled proteins with S. aureus V8 protease or trypsin followed by analysis of peptides in two dimensions. For immunological comparison, antisera were used that had been raised in rabbits using electrophoretically purified MAP-1 and MAP-2 components as immunogens. As determined by immunoprecipitation, the antiserum raised to MAP-1 was equally reactive with MAP-1 and MAP-2 components, whereas the antiserum to MAP-2 reacted primarily with MAP-2. Indicating the presence of common as well as unique antigenic determinants on MAP-1 and MAP-2, these results, therefore, were in agreement with the peptide mapping data. Implications of these results for biosynthetic mechanisms as well as differential distribution and functions of MAPs in cells are discussed.
Intermated mapping populations are expected to result in high mapping resolution for tightly linked loci. The objectives of our study were to (1) investigate the consequences of constructing linkage maps from intermated populations using mapping methods developed for F(2) populations, (2) compare linkage maps constructed from intermated populations (F(2)Syn3) with maps generated from corresponding F(2) and F(3) base populations, and (3) investigate the advantages of intermated mapping populations for applications in plant breeding programs. We constructed linkage maps for two European flint maize populations (A x B, C x D) by mapping 105 SSR markers in generations F(2) and F(2)Syn3 of population A x B, and 102 SSR markers in generations F(3) and F(2)Syn3 of population C x D. Maps for F(2)Syn3 were constructed with mapping methods for F(2) populations (Map A) as well as with those specifically developed for intermated populations (Map B). Both methods relate map distances to recombination frequencies in a single meiosis and, therefore, did not show a map expansion in F(2)Syn3 compared with maps constructed from the respective F(2) or F(3) base populations. Map A and B differed considerably, presumably because of theoretical shortcomings of Map A. Since loosely linked markers could not unambiguously be mapped in the F(2)Syn3 populations, they may hamper the construction of linkage maps from intermated populations.
Microtubules from neural tissues of the Atlantic cod, Gadus morhua, and of several species of Antarctic teleosts are composed of tubulin and several microtubule-associated proteins (MAPs), one of which has an apparent molecular weight of approximately 400-430 kDa. Because its apparent molecular weight exceeds those of the MAP 1 proteins, we designate this high molecular weight teleost protein MAP 0. Cod MAP 0 failed to cross-react with antibodies specific for MAPs 1A, 1B and 2 of mammalian brain, for MAP H1 of squid optic lobe, and for chicken erythrocyte syncolin, which suggests that it has a novel structure. Similarly, MAP 0 from the Antarctic fish was not recognized by an antibody specific for bovine MAP 2. Together, these observations suggest that MAP 0 is a novel MAP that may be unique to fish. To determine the tissue specificity and phylogenetic distribution of this protein, we generated a rabbit polyclonal antibody against cod MAP 0. Using this antibody, we found that MAP 0 was present in microtubule proteins isolated from cod brain tissues and spinal cord but was absent in microtubules from heart, liver, and spleen. At the subcellular level, MAP 0 was distributed in cod brain cells in a punctate pattern coincident with microtubules but was absent in skin cells. MAP 0 was also detected in cells of the peripheral nervous system. A survey of microtubule proteins from chordates and invertebrates showed that anti-MAP 0-reactive homologs were present in five teleost species but not in more primitive fish and invertebrates or in higher vertebrates. MAP 0 bound to cod microtubules by ionic interaction at a site recognized competitively by bovine MAP 2. Although its function is unknown, MAP 0 does not share the microtubule-binding properties of the motor proteins kinesin and dynein. We propose that MAP 0 is a unique, teleost-specific MAP.
Contour map learning may require three-dimensional representation of the area depicted by a contour map. The purpose of the study was to test the hypothesis that participants created three-dimensional mental representations of contour maps when asked to generate a cross-section profile of the map terrain from one point on the contour map to another. Gender differences in cross-section performance were also investigated, and it was hypothesized that males would perform better than females in a contour map cross-section test. Participants studied a series of contour maps or landsurface maps (three-dimensional drawings of an area), and answered two cross-section questions per map. Following the cross-section test, participants were given an incidental recognition test for the previously studied maps, either in a contour map format or a landsurface map format. Males recognized the landsurface maps corresponding to the contour map cross-section questions answered correctly better than contour map cross-section questions answered incorrectly, whereas females did not. This finding suggested that males, but not females, formed three-dimensional representations of the contour maps. There were no gender differences in performance on the contour map cross-section test, but males achieved higher recognition scores than females when the cross-section stimuli were contour maps. It was concluded that multiple spatial and verbal processing strategies can be used successfully to solve a contour map cross-section test, but that three-dimensional spatial processing may be more efficient than other forms of processing for long-term memory of contour maps. Copyright 1998 Academic Press.
A first-generation radiation hybrid (RH) map of the equine (Equus caballus) genome was assembled using 92 horse x hamster hybrid cell lines and 730 equine markers. The map is the first comprehensive framework map of the horse that (1) incorporates type I as well as type II markers, (2) integrates synteny, cytogenetic, and meiotic maps into a consensus map, and (3) provides the most detailed genome-wide information to date on the organization and comparative status of the equine genome. The 730 loci (258 type I and 472 type II) included in the final map are clustered in 101 RH groups distributed over all equine autosomes and the X chromosome. The overall marker retention frequency in the panel is approximately 21%, and the possibility of adding any new marker to the map is approximately 90%. On average, the mapped markers are distributed every 19 cR (4 Mb) of the equine genome--a significant improvement in resolution over previous maps. With 69 new FISH assignments, a total of 253 cytogenetically mapped loci physically anchor the RH map to various chromosomal segments. Synteny assignments of 39 gene loci complemented the RH mapping of 27 genes. The results added 12 new loci to the horse gene map. Lastly, comparison of the assembly of 447 equine genes (256 linearly ordered RH-mapped and additional 191 FISH-mapped) with the location of draft sequences of their human and mouse orthologs provides the most extensive horse-human and horse-mouse comparative map to date. We expect that the foundation established through this map will significantly facilitate rapid targeted expansion of the horse gene map and consequently, mapping and positional cloning of genes governing traits significant to the equine industry.
The nervous system performs computations to process information that is biologically important. Some of these computations occur in maps--arrays of neurons in which the tuning of neighboring neurons for a particular parameter value varies systematically. Computational maps transform the representation of information into a place-coded probability distribution that represents the computed values of parameters by sites of maximum relative activity. Numerous computational maps have been discovered, including visual maps of line orientation and direction of motion, auditory maps of amplitude spectrum and time interval, and motor maps of orienting movements. The construction of the auditory map of space is the most thoroughly understood: information about interaural delays and interaural intensity differences is processed in parallel by separate computational maps, and the outputs of these maps feed into a higher order processor that integrates sets of cues corresponding to sound source locations and creates a map of auditory space. Computational maps represent ranges of parameter values that are relevant to the animal, and may differentially magnify the representation of values that are of particular importance. The tuning of individual neurons for values of a mapped parameter is broad relative to the range of the map. Consequently, neurons throughout a large portion of a computational map are activated by any given stimulus, and precise information about the mapped parameter is coded by the locations of peak activity. There are a number of advantages of performing computations in maps. First, information is processed rapidly because the computations are preset and are executed in parallel. Second, maps simplify the schemes of connectivity required for processing and utilizing the information. Third, a common, mapped representation of the results of different kinds of computations allows the nervous system to employ a single strategy for reading the information. Finally, maps enable several classes of neuronal mechanisms to sharpen tuning in a manner not possible for information that is represented in a non-topographic code.
BACKGROUND: Bovine chromosome (BTA) 15 contains a quantitative trait loci (QTL) for meat tenderness, as well as several breaks in synteny with human chromosome (HSA) 11. Both linkage and radiation hybrid (RH) maps of BTA 15 are available, but the linkage map lacks gene-specific markers needed to identify genes underlying the QTL, and the gene-rich RH map lacks associations with marker genotypes needed to define the QTL. Integrating the maps will provide information to further explore the QTL as well as refine the comparative map between BTA 15 and HSA 11. A recently developed approach to integrating linkage and RH maps uses both linkage and RH data to resolve a consensus marker order, rather than aligning independently constructed maps. Automated map construction procedures employing this maximum-likelihood approach were developed to integrate BTA RH and linkage data, and establish comparative positions of BTA 15 markers with HSA 11 homologs. RESULTS: The integrated BTA 15 map represents 145 markers; 42 shared by both data sets, 36 unique to the linkage data and 67 unique to RH data. Sequence alignment yielded comparative positions for 77 bovine markers with homologs on HSA 11. The map covers approximately 32% of HSA 11 sequence in five segments of conserved synteny, another 15% of HSA 11 is shared with BTA 29. Bovine and human order are consistent in portions of the syntenic segments, but some rearrangement is apparent. Comparative positions of gene markers near the meat tenderness QTL indicate the region includes separate segments of HSA 11. The two microsatellite markers flanking the QTL peak are between defined syntenic segments. CONCLUSIONS: Combining data to construct an integrated map not only consolidates information from different sources onto a single map, but information contributed from each data set increases the accuracy of the map. Comparison of bovine maps with well annotated human sequence can provide useful information about genes near mapped bovine markers, but bovine gene order may be different than human. Procedures to connect genetic and physical mapping data, build integrated maps for livestock species, and connect those maps to more fully annotated sequence can be automated, facilitating the maintenance of up-to-date maps, and providing a valuable tool to further explore genetic variation in livestock.
The rat (Rattus norvegicus) is an important experimental model for many human diseases including arthritis, diabetes, and other autoimmune and chronic inflammatory diseases. The rat genetic linkage map, however, is less well developed than those of mouse and human. Integrated rat genetic linkage maps have been previously reported by Pravenec et al. (1996, Mamm. Genome 7: 117-127) (500 markers mapped in one cross), Bihoreau et al. (1997, Genome Res. 7: 434-440) (767 markers mapped in three crosses), Wei et al. (1998, Mamm. Genome 9: 1002-1007) (562 markers mapped in two crosses), Brown et al. (1998, Mamm. Genome 9: 521-530) (678 markers mapped in four crosses), and Nordquist et al. (1999, Rat Genome 5: 15-20) (330 markers mapped in two crosses). The densest linkage map combined with a radiation hybrid map, reported by Steen et al. (1999, Genome Res. 9: AP1-AP8), includes 4736 markers mapped in two crosses. Here, we present an integrated linkage map with 1137 markers. We have constructed this map by genotyping F2 progeny of five crosses: F344/NHsd x LEW/NHsd (673 markers), DA/Bkl x F344/NHsd (531 markers), BN/SsN x LEW/N (714 markers), DA/Bkl x BN/SsNHsd (194 markers), and DA/Bkl x ACI/SegHsd (245 markers). These inbred rat strains vary in susceptibility/resistance to multiple autoimmune diseases and are used extensively for many types of investigation. The integrated map includes 360 loci mapped in three or more crosses. The map contains 196 new SSLP markers developed by our group, as well as many SSLP markers developed by other groups. Two hundred forty genes are incorporated in the map. This integrated map should allow comparison of rat genetic maps from different groups and thereby facilitate genetic studies of rat autoimmune and related disease models.
CONTEXT: Tools to assess the evolving conceptual framework of physicians-in-training are limited, despite their critical importance to physicians' evolving clinical expertise. Concept mapping assessment (CMA) enables teachers to view students' organization of their knowledge at various points in training. OBJECTIVE: To assess whether CMA reflects expected differences and changes in the conceptual framework of resident physicians, whether concept maps can be scored reliably, and how well CMA scores relate to the results of standard in-training examination. DESIGN, SETTING, AND PARTICIPANTS: A group of 21 resident physicians (9 first-year and 12 second- and third-year residents) from a university-based pediatric training program underwent concept map training, drew a preinstruction concept map about seizures, completed an education course on seizures, and then drew a postinstruction map. Maps were scored independently by 3 raters using a standardized method. The study was conducted in May and June 1999. MAIN OUTCOME MEASURES: Preinstruction map total scores and subscores in 4 categories compared with postinstruction map scores; map scores of second- and third-year residents compared with first-year residents; and interrater correlation of map scores. RESULTS: Total CMA scores increased after instruction from a mean (SD) preinstruction map score of 429 (119) to a mean postinstruction map score of 516 (196) (P =.03). Second- and third-year residents scored significantly higher than first-year residents before instruction (mean [SD] score of 472 [116] vs 371 [102], respectively; P =.04), but not after instruction (mean [SD] scores, 561 [203] vs 456 [179], respectively; P =.16). Second- and third-year residents had greater preinstruction map complexity as measured by cross-link score (P =.01) than first-year residents. The CMA score had a weak to no correlation with the American Board of Pediatrics In-training Examination score (r = 0.10-0.54). Interrater correlation of map scoring ranged from weak to moderate for the preinstruction map (r = 0.51-0.69) and moderate to strong for the postinstruction map (r = 0.74-0.88). CONCLUSIONS: Our data provide preliminary evidence that concept mapping assessment reflects expected differences and change in the conceptual framework of resident physicians. Concept mapping assessment and standardized testing may measure different cognitive domains. JAMA. 2000;284:1105-1110
The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.
The purpose of this study is to compare speech perception performance in Mandarin-speaking Nucleus CI24 implantee using standard behavior MAPs and NRT-based MAPs. Eight Nucleus CI24 users (5 years and older) participated in the study. They all fulfilled the following criteria: (1) behavioral MAP and NRT thresholds can be reliably obtained; (2) had more than 18 functioning electrodes; (3) had at least 6 months experience using CI. All subjects received speech evaluation under three different MAPs: a traditional behavioral MAP, a MAP predicted from the NRT thresholds of the E22 (electrode 22), E19, E15, E11, E8, E5, E1 and a combined MAP based on the information of NRT thresholds and behavioral threshold/comfortable levels of the E11. The speech evaluation package included word recognition test in quiet, in noise, and a Mandarin sentence test in quiet. Results showed that three MAPs are similar in some subjects, but different in other subjects. Compared to the NRT MAPs, the combined MAPs are more similar to the behavioral MAPs. There was no significant difference in the mean score of the word recognition test in quiet, in noise and sentence test under these three MAP conditions. In conclusion, although the behavioral MAPs and the NRT-based MAPs are not identical, the speech performance of Mandarin-speaking CI24 implantee using MAPs predicted from NRT thresholds appeared to be no worse than the traditional behavioral MAPs. Therefore, in certain cases that behavioral MAPs are difficult to obtain (such as in very young or multiple handicapped children), NRT-based MAPs may serve reliably as an initial estimation.
Genetic maps play an important role in gene mapping. Inaccurate genetic maps can hinder gene mapping by biasing lod scores and reducing the power to map a trait to a particular region. Although sequence-based physical maps can provide a unique order for markers, they do not provide information on genetic map distances. By simulation studies, I investigated how many meioses are necessary to accurately estimate genetic map distances for maps constructed from microsatellite and single-nucleotide polymorphism (SNP) markers for various intermarker distances and marker heterozygosity. To evaluate the accuracy of the generated genetic maps, the length of the 95% confidence interval for intermarker genetic distances was examined. In addition, the power to separate two adjacent markers by a nonzero map distance was investigated. The number of meioses necessary to accurately estimate map distances depends greatly not only on intermarker distances but also on marker heterozygosity. For example, for a genetic map with intermarker distances of 0.5 cM generated with 1,000 meioses, when marker heterozygosity was high (0.90), for 96% of the markers there was a nonzero map distance between adjacent markers. However, when marker heterozygosity was low (0.32), only 48% of the markers mapped to a unique position. For identical numbers of meioses and intermarker distances, genetic maps constructed from microsatellite markers will be more precise than maps assembled from SNP markers, due to the higher levels of heterozygosity for microsatellite markers.
BACKGROUND: Human chromosome 11 is one of the autosomes on which many disease genes have been mapped. Many different types of map, including a radiation hybrid map, a genetic map, and an STS-content YAC map, have been constructed for the chromosome. However, a physical map providing accurate physical distances has not yet been established. A chromosome-wide NotI restriction map was constructed to understand the overall feature of the genome organization and to facilitate the positional cloning of disease genes. RESULTS: A complete NotI restriction map of the entire long arm of human chromosome 11 was constructed using linking-clone mapping. This physical map covers 77.6Mb, from a pericentromeric NotI site to the terminus, and provides the most accurate ordering and distance estimation to date. We also mapped 138 sequence markers in the q13 region that have been poorly mapped previously. CONCLUSIONS: The restriction map of the entire long arm of human chromosome 11 is the longest restriction map of the human genome. This mapping has disclosed unique features regarding the organization of the chromosome, indicating that restriction sites of NotI, a CpG-recognition enzyme, are primarily distributed in R (or T) bands and that genetic distance is considerably longer in R (or T) bands than in G bands. The mapping, as well as the dense concentration of mapped markers within the q13 region, should help with positional cloning of the genes associated with various diseases.