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Brain maps and parallel computers.

It is well known that neural responses in many brain regions are organized in characteristic spatial patterns referred to as brain maps. It is likely that these patterns in some way reflect aspects of the neural computations being performed, but to date there are no general guiding principles for relating the structure of a brain map to the properties of the associated computation. In the field of parallel computing, maps similar to brain maps arise when computations are distributed across the multiple processors of a parallel computer. In this case, the relationship between maps and computations is well understood and general principles for optimally mapping computations onto parallel computers have been developed. In this paper we discuss how these principles may help illuminate the relationship between maps and computations in the nervous system.

Brain

Reference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions.

A highly reproducible, commercial and nonlinear, wide-range immobilized pH gradient (IPG) was used to generate two-dimensional (2-D) gel maps of [35S]methionine-labeled proteins from noncultured, unfractionated normal human epidermal keratinocytes. Forty one proteins, common to most human cell types and recorded in the human keratinocyte 2-D gel protein database were identified in the 2-D gel maps and their isoelectric points (pI) were determined using narrow-range IPGs. The latter established a pH scale that allowed comparisons between 2-D gel maps generated either with other IPGs in the first dimension or with different human protein samples. Of the 41 proteins identified, a subset of 18 was defined as suitable to evaluate the correlation between calculated and experimental pI values for polypeptides with known composition. The variance calculated for the discrepancies between calculated and experimental pI values for these proteins was 0.001 pH units. Comparison of the values by the t-test for dependent samples (paired test) gave a p-level of 0.49, indicating that there is no significant difference between the calculated and experimental pI values. The precision of the calculated values depended on the buffer capacity of the proteins, and on average, it improved with increased buffer capacity. As shown here, the widely available information on protein sequences cannot, a priori, be assumed to be sufficient for calculating pI values because post-translational modifications, in particular N-terminal blockage, pose a major problem. Of the 36 proteins analyzed in this study, 18-20 were found to be N-terminally blocked and of these only 6 were indicated as such in databases. The probability of N-terminal blockage depended on the nature of the N-terminal group. Twenty six of the proteins had either M, S or A as N-terminal amino acids and of these 17-19 were blocked. Only 1 in 10 proteins containing other N-terminal groups were blocked.

Amino Acid Sequence

A combined genetic and radiation hybrid map surrounding the Treacher Collins syndrome locus on chromosome 5q.

The distal region of chromosome 5q contains a large number of genes, including those implicated in a variety of Mendelian disorders. One of these, Treacher Collins syndrome (TCOF1), is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Previous studies have localized the TCOF1 locus between D5S519 (proximal) and SPARC (distal). To more accurately define the genetic distance between these markers, and to extend a high resolution genetic map of 5q31-33 to include additional highly informative markers, 15 loci (including polymorphisms for 4 known genes) were mapped through the Centre d'Etude du Polymorphisme Humain reference pedigrees. The resulting genetic map encompasses 29 cM on the sex-averaged map. To help integrate this linkage map with a physical map of the region, 13 loci from 5q31--33, including 6 genes, were used to construct a radiation hybrid map. As eight of the loci are common to both maps this has allowed us to combine the maps. The most likely location for the TCOF1 locus within this marker framework is in the D5S519-SPARC interval; a region estimated to be approximately 880 kb.

Animals

The effect of reference-electrode choice on the spatial resolution of topographical potential maps in the discrimination of deep cerebral sources.

Although scalp potential distributions do not uniquely determine the location and configuration of neural generators, they are important because they provide the necessary conditions that any hypothesized sources must satisfy and suggest a basis for testing alternate source hypotheses. One problem that could confound the correct interpretation of scalp potentials is the choice of reference electrode. Changing the reference may make activity patterns and waveform components appear and disappear (Pascual-Marqui et al. (1988) Int. J. Neurosci., 43: 237-249). The cortical imaging technique (CIT), a method for approximating potential fields on the cortical surface, was used to test the effects of the choice of reference electrode on these fields. Simulated and empirical evoked potential scalp-recorded referential data were mathematically analyzed for the case in which the reference (linked-ears) was arbitrarily assumed to be at zero potential, and the case in which the reference was the 'average' electrode, the arithmetic mean of all of the scalp-recorded voltages in the referential montage. The results for the two references were similar. This is encouraging because potential measurements relative to a point at infinity (zero potential) are never available and the assumption that any actual reference used for a recording is at zero potential is therefore suspect.

Animals

A YAC contig map of Arabidopsis thaliana chromosome 3.

We have constructed a YAC contig map of Arabidopsis thaliana chromosome 3. From an estimated total size of 25 Mb, about 21 Mb were covered by 148 clones arranged into nine YAC contigs, which represented most of the low-copy regions of the chromosome. YAC clones were anchored with 259 molecular markers, including 111 for which linkage information was previously available. Most of the genetic map was included in the YAC coverage, and more than 60% of the genetic markers from the reference recombinant inbred line map were anchored, giving a high level of integration between the genetic and physical maps. The submetacentric structure of the chromosome was confirmed by physical data; 3R (the top arm of the linkage map) was about 12 Mb, and 3L (the bottom arm of the linkage map) was about 9 Mb. This YAC physical map will aid in chromosome walking experiments and provide a framework for large-scale DNA sequencing of chromosome 3.

Arabidopsis

Reporting levels of spinal blockade.

With spinal anesthesia the level of surgical analgesia is mostly reported without reference to the neuroanatomic map of spinal nerves. The classical maps are variably and inconsistently reported in many textbooks. Because of the differences between the classical maps of Keegan and Garrett and of Foerster, and also because of the variability in their interpretation, we applied them to the same clinical data. This resulted in a theoretically clinically significant difference of two segments. It is concluded that clear reference should be made to the implemented segmental map in expressing the level of spinal blockade.

Anesthesia, Obstetrical

Index, comprehensive microsatellite, and unified linkage maps of human chromosome 14 with cytogenetic tie points and a telomere microsatellite marker.

Three sets of linkage maps (index, comprehensive microsatellite, and unified) have been constructed for human chromosome 14 based on genotypes from the CEPH reference pedigrees. The index maps consist of 18 microsatellite markers, with heterozygosities of at least 68% and intermarker spacing no greater than 11 cM. The sex-average comprehensive microsatellite map is 125 cM in length and includes 115 markers with 54 loci uniquely placed with odds for marker order of at least 1000:1. The sex-average index map length is 121 cM, and the female- and male-specific maps are 143 and 101 cM, respectively. A unified map was also constructed from 147 loci (162 marker systems), which includes 32 RFLP markers in addition to the 115 microsatellites. The sex-average length of the unified map is 128 cM with 69 loci uniquely placed. Our maps are anchored by a microsatellite telomere marker sCAW1 (D14S826), developed from a telomere YAC clone TYAC196, which extends the linkage map to the physical terminus of the long arm of chromosome 14. Furthermore, we have also physically mapped seven of the loci by fluorescence in situ hybridization of cosmid clones or Alu-PCR products amplified from YACs containing the marker sequences. Together with previously established cytogenetic map designations for other loci, our maps display links between genetic markers for 10 of 13 cytogenetic bands of chromosome 14 at the 550 genome band resolution.

Base Sequence

A genetic map of human chromosome 17p.

A genetic linkage map was constructed with 18 loci from the short arm and pericentric region of chromosome 17 typed on the CEPH reference families. The genetic map includes three markers extracted from the CEPH public database. Nine loci could be ordered using a threshold of odds of at least 1000:1 against alternative orders during the map construction process. With a reduced tolerance of 100:1, a total of 13 loci could be placed on the map spanning a distance of approximately 60 cM in females and 46 cM in males. There were statistically significant differences between the male and the female genetic maps. The order inferred from the genetic data was consistent with the physical localizations of these probes obtained from somatic cell hybrids and tumor deletion studies. This map should be useful for genetic fine mapping of 17p loci.

Alleles

Toward a unified approach to genetic mapping of eukaryotes based on sequence tagged microsatellite sites.

The genomes of all eukaryotes appear to contain a special class of loci, termed microsatellites, which can serve, if sequenced and taken as the substrate for the polymerase chain reaction, as highly informative, locus-specific markers. By analogy to the "sequence tagged sites" recently proposed by Olsen et al. for standardizing the human physical gene map, these microsatellite markers are termed "sequence tagged microsatellite sites" (STMS). Genetic maps based on STMS will share with the Olsen physical maps the advantage that mapping vocabularies will be standardized to the DNA sequence base and that access to any particular locus will not require shipping or storing cloned probes. The species map will consist simply of a listing of nucleotide sequences. Reference populations for developing STMS maps can be chosen on the basis of biological or economic interest. It will not be necessary to maximize for genetic divergence.

Animals

Microsatellite markers for genetic mapping in the chicken.

Microsatellite markers have been found to be abundant, evenly distributed, and highly polymorphic in a number of eukaryotic genomes. The objective of this study was to determine the utility of (TG)n microsatellites in the chicken. A chicken library enriched for (TG)n repeats was generated and 42 unique clones containing (TG)n microsatellites were identified and sequenced. The number of uninterrupted TG repeats ranged from 4 to 14 with an average of 7.8, which was considerably less than the number of repeats found in mammalian species. When primers designed to amplify across the (TG)n microsatellites were used in polymerase chain reactions (PCR) containing genomic chicken DNA, 19 of the 33 primer sets examined yielded polymorphisms in at least one of the three sets of chicken families: 15, 11, and 11 primer sets detected polymorphisms in the East Lansing (EL) reference population, the Compton (C) reference family, and between Line 63 and Line 72 chickens, respectively. The polymorphic microsatellite markers in the EL and C reference families were genetically mapped. Nine and seven mapped markers in the EL and C reference families, respectively, are polymorphic between Line 63 and Line 72, indicating that microsatellite markers will greatly enhance the ability to genotype specific loci of any chicken population.

Animals

Subregional mapping of the human lymphocyte-specific protein tyrosine kinase gene (LCK) to 1p35-->p34.3 and its position relative to the 1p marker D1S57.

The LCK gene encodes a lymphocyte-specific member of the Src family of protein tyrosine kinases. This gene was previously assigned to human chromosome region 1p35-->p32 by isotopic in situ hybridization. We report here its more refined localization to bands 1p35-->p34.3 by fluorescence in situ hybridization on R-banded metaphase chromosomes and its mapping relative to the reference marker pYNZ2 (D1S57).

Base Sequence

Polymerase chain reaction-based polymorphisms in the porcine cholecystokinin (CCK) gene and assignment to chromosome 13.

Polymorphisms were identified in the porcine cholecystokinin (CCK) gene by digestion of products from polymerase chain reaction (PCR) with the restriction enzyme DpnII. Individuals from the European pig gene mapping project (PiGMaP) consortium reference families (eight full-sib families, 91 total progeny) were genotype to determine linkage relationships between the CCK gene and previously mapped loci. Linkage analysis revealed that the CCK gene is located on porcine chromosome 13.

Animals

Topographic mapping of brain electromagnetic signals: a review of current technology.

Topographic mapping of brain electromagnetic signals has become increasingly popular in recent years both as a clinical tool and as an area of research in its own right. The capabilities of existing computerized systems for displaying such maps and for performing localization of current sources in the brain have continued to expand. In this paper we review some of the methodological and technological issues concerning topographic mapping. These include issues of choice of interpolation algorithm, what to map, head geometry, EEG reference location, and scaling. We also discuss characteristics of clinical databases for patient comparison and the usefulness of quantitative EEG (which includes mapping) for the diagnosis of nervous system disorders. Finally, we compare five representative systems in terms of their topographic mapping capabilities. The overall conclusion is that future developments must make use of integrated data from other neuroimaging technologies such as MRI, PET, and SPECT, and determination of the normal limits of topographic parameters must be more carefully examined.

Brain Mapping

Clinical utility of topographic EEG brain mapping.

Topographic EEG brain mapping was performed on 100 patients referred for both EEG and neuroimaging procedures. Topographic maps were abnormal in 78% of patients with stroke, 50% with head trauma and 100% of those with space occupying lesions (tumor, abscess or intracerebral hematoma). Of the patients with abnormal EEG maps 30% had either sole or better localization with mapping than routine EEG or neuroimaging procedures. In no cases were there false localizing abnormalities by EEG mapping. Topographic mapping appears to provide better detection of low amplitude slow activity not easily discernible by routine EEG. It also provides faithful correspondence with localization of many lesions on neuroimaging procedures, and at times distinguishes abnormalities not immediately definable by CT/MRI. Topographic EEG mapping is a valuable adjunct to routine EEG.

Adolescent

A 30-Mb metric fluorescence in situ hybridization map of human chromosome 19q.

A high-resolution metric physical map of chromosome 19q has been constructed by fluorescence in situ hybridization. The map locates 136 cosmid reference points that span 30 Mb. The reference points are sequentially ordered from centromere to telomere, and the distance between neighboring cosmids is known from 240 partially overlapping, redundant estimates of genomic distances in kilobases separating pairs of cosmids. The average spacing between cosmid reference points is 220 kb, with over 75% of intervals less than 300 kb. Eighty-four genes and polymorphic markers have been assigned to mapped cosmids. The information on order and genomic distances separating pairs of cosmids, both key elements for building physical maps, has furthered the construction and integration of the genetic and physical maps of chromosome 19.

Chromosome Mapping

A genetic and physical map of bovine chromosome 11.

A genetic map of bovine Chromosome (Chr) 11 (BTA11, synteny group U16) has been constructed from 330 animals belonging to 21 families, which constitute the international bovine reference panel (IBRP). This map is based on 13 polymorphic microsatellite markers, two of which were chosen in previously published maps. Three markers have been isolated from cosmids. Two of the three cosmids have been physically localized by fluorescence in situ hybridization (FISH), to anchor the genetic map on the chromosome. In addition, a biallelic polymorphism in the beta-lactoglobulin gene (LGB) has been genetically positioned relative to the microsatellite markers. The most probable order of the markers is: cen-INRA044-BM716-INRA177-(TGLA327, INRA198, INRA131)-INRA111-INRABERN169-(INRA115, INRA032)-INRA108-INRABERN162-INRA195-LGB. The total linkage group spans 126 cM, which probably corresponds to most of the chromosome length. The average intermarker distance is about 10.5 cM, allowing the potential detection of a genetic linkage with any Economic Trait Loci (ETL) of this chromosome. Seven of these markers have been previously published by Vaiman and coworkers (1994), two will be published as part of a set of markers (Eggen et al. in preparation), two are described in this paper, and two (BM716, TGLA327) were chosen from the published maps of BTA11 in order to integrate our data with existing maps. All these markers were assigned to synteny group U16 by use of a previously characterized panel of hamster/bovine somatic hybrid cell lines (Guérin et al. 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals