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Deletions in bacteriophage P2. Circularity of the genetic map and its orientation relative to the DNA denaturation map.

Several types of viable chromosomal deletions of bacteriophage P2 were isolated. One type gives the immunity insensitive phenotype and may extend to the genes for the immunity repressor (C) and for integrative recombination (int). Two other types delete genes (old and fun) known to be active in the lysogenic state. For such deletion mutants the relationship between particle density and DNA length was established. The deletions were located in respect to previously mapped genes and the results were compared with electron microscopical studies (by Inman and collaborators) of the P2 chromosome. It is concluded that the best representation of the genetic map of P2 is circular. The cohesive ends of the linear P2 DNA molecule are most likely formed between genes old and Q. Except for the neighborhood of gene old, the previously published, linear genetic map of P2 (Lindahl) is colinear with the melting map of the P2 chromosome (Inman). Preliminary evidence for some specific recombination event often accompanying integrative recombination between phage chromosomes is presented.

Bacteriophage P2↗

Restriction mapping of DNA of temperate Rhizobium meliloti phage 16-3: comparison of genetic and physical maps indicates a long, genetically silent chromosomal arm.

The complete restriction map of DNA (61.57 Kb) of temperate Rhizobium meliloti phage 16-3 has been constructed for enzymes BglII, HindIII, HpaI, KpnI, and a partial map for EcoRI. The strategy employed for mapping included the analysis of double, triple and partial digests; comparison of wild type and deletion mutants; and detailed analysis of subfragments, exploiting the presence of cohesive ends of the phage. Comparison of the genetic and physical maps indicates that one arm of the chromosome is genetically silent and/or contains nonessential genes.

Bacteriophages↗

Genetic maps of eight linkage groups of Aspergillus niger based on mitotic mapping.

This paper provides a genetic map of Aspergillus niger. At present 84 markers have been assigned to eight linkage groups. The chromosomal location of 60 markers is presented in this paper. The allocation of markers is based on recombination due to mitotic crossing over. Various methods for selection and analysis of homozygous recombinants were applied, using colour, auxotrophic and resistance markers. In addition, transformants carrying the heterologous Aspergillus nidulans gene coding for acetamidase (amdS) were used for mitotic mapping of markers in several linkage groups. In most of the transformants the amdS insert appeared to be centromere-distal to all known genetic markers, thus extending the genetic map. The linear order of the markers in the eight linkage groups has been determined. On the basis of these and earlier experiments tentative genetic maps for the eight linkage groups are presented. Genetic markers were found on both arms of the chromosomes, except for chromosomes II and IV. The genetic distance between markers and the centromere varies from about 10(-4) (LG I, II, V) up to more than 10(-2) (LG III, VI, VIII). The total frequency of mitotic recombination per genome in this fungus has been estimated to be at least 1.2 x 10(-1).

Amidohydrolases↗

Spatial resolution of body surface potential maps and magnetic field maps: a simulation study applied to the identification of ventricular pre-excitation sites.

The spatial resolution of body surface potential maps (BSPMs) and magnetic field maps (MFMs) is investigated by means of an anatomically accurate computer model of the human ventricular myocardium. BSPMs and MFMs are calculated for the simulated activation sequences initiated at 35 pre-excitation sites located along the atrioventricular (AV) ring of the epicardium. Changes in the BSPMs and MFMs corresponding to different pre-excitation sites are quantified in terms of the correlation coefficient r. The spatial resolution (selectivity) for a given pre-excitation site is defined as the half-distance between those neighbouring locations at which morphological features of maps, in terms of r, become distinct (r < 0.95). It is found that, at 28 ms after the onset of pre-excitation and with no noise added, this distance +/- SD, for all sites along the AV ring for the 117-lead BSPMs, is 0.83 +/- 0.32 cm, and for the 64-lead and 128-lead MFMs it is 1.54 +/- 0.84 cm and 1.15 +/- 0.43 cm, respectively. The findings suggest that, when features of non-invasively recorded electrocardiographic and magnetocardiographic map patterns are used for identifying accessory pathways in patients suffering from WPW syndrome, BSPMs are likely to provide more detailed information for guiding the ablative treatment than MFMs. For some sites MFMs provide more information. Both modalities may provide additional assistance to the cardiologist in locating the site of the accessory pathway.

Body Surface Potential Mapping↗

QTL mapping of Fusarium moniliforme ear rot resistance in maize. 1. Map construction with microsatellite and AFLP markers.

To map the QTLs of Fusarium moniliforme ear rot resistance in Zea mays L., a total of 230 F2 individuals, derived from a single cross between inbred maize lines R15 (resistant) and Ye478 (susceptible), were genotyped for genetic map construction using simple sequence repeat (SSR) markers and amplified fragment length polymorphism (AFLP) markers. We used 778 pairs of SSR primers and 63 combinations of AFLP primers to detect the polymorphisms between parents, R15 and Ye478. From the polymorphic 30 AFLP primer combinations and 159 SSR primers, we scored 260 loci in the F2 population, among which 8 SSR and 13 AFLP loci could not be assigned to any of the linkage groups. An integrated molecular genetic linkage map was constructed by the remaining 151 SSR and 88 AFLP markers, which distributed throughout the 10 linkage groups of maize and spanned the genome of about 3463.5 cM with an average of 14.5 cM between two markers. On 4 chromosomes, we detected 5 putative segregation distortion regions (SDRs), including 2 new ones (SDR2 and SDR7). The other 3 SDRs were located near the regions where gametophyte genes were mapped, indicating that segregation distortion could be partially caused by gametophytic factors.

Chromosome Mapping↗

Development of a black gram [Vigna mungo (L.) Hepper] linkage map and its comparison with an azuki bean [Vigna angularis (Willd.) Ohwi and Ohashi] linkage map.

The Asian Vigna group of grain legumes consists of six domesticated species, among them black gram is widely grown in South Asia and to a lesser extent in Southeast Asia. We report the first genetic linkage map of black gram [Vigna mungo (L.) Hepper], constructed using a BC(1)F(1) population consisting of 180 individuals. The BC(1)F(1) population was analyzed in 61 SSR primer pairs, 56 RFLP probes, 27 AFLP loci and 1 morphological marker. About 148 marker loci could be assigned to the 11 linkage groups, which correspond to the haploid chromosome number of black gram. The linkage groups cover a total of 783 cM of the black gram genome. The number of markers per linkage group ranges from 6 to 23. The average distance between adjacent markers varied from 3.5 to 9.3 cM. The results of comparative genome mapping between black gram and azuki bean show that the linkage order of markers is highly conserved. However, inversions, insertions, deletions/duplications and a translocation were detected between the black gram and azuki bean linkage maps. The marker order on parts of linkage groups 1, 2 and 5 is reversed between the two species. One region on black gram linkage group 10 appears to correspond to part of azuki bean linkage group 1. The present study suggests that the azuki bean SSR markers can be widely used for Asian Vigna species and the black gram genetic linkage map will assist in improvement of this crop.

Agriculture↗

Map Manager QTX, cross-platform software for genetic mapping.

Map Manager QTX (QTX) is software for analysis of genetic mapping experiments in experimental plants and animals. It includes functions for mapping both Mendelian and quantitative trait loci. QTX is an enhanced version of Map Manager QT, rewritten with the aid of cross-platform libraries (XVT, Boulder Software Foundry, Inc.), which allow it to be compiled for multiple computer platforms. It currently is distributed for Microsoft Windows and Mac OS and is available at http://mapmgr.roswellpark.org/mmQTX.html.

Animal Population Groups↗

Further studies on using multiple-cross mapping (MCM) to map quantitative trait loci.

We have completed whole-genome scans for quantitative trait loci (QTLs) associated with acute ethanol-induced activation in the six F(2) intercrosses that can be formed from the C57BL/6J (B6), DBA/2J (D2) , BALB/cJ (C), and LP/J (LP) inbred strains. The goal was to test the hypothesis that given the relatively simple structure of the laboratory mouse genome, the same QTLs will be detected in multiple crosses which in turn will provide support for the strategy of multiple-cross mapping (MCM). QTLs with LOD scores greater than 4 were detected on Chrs 1, 2, 3, 8, 9, 13, 14, and 16. Only for the QTL on distal Chr 1 was there convincing evidence that the same or at least a very similar QTL was detected in multiple crosses. We also mapped the Chr 2 QTL directly in heterogeneous stock (HS) animals derived from the four inbred strains. At G(19) the QTL was mapped to an approximately 3-Mbp interval and this interval was associated with a haplotype block with a largely biallelic structure: B6-L:C-D2. We conclude that mapping in HS animals not only provides significantly greater QTL resolution, at least in some cases it provides significantly more information about the QTL haplotype structure.

Animals↗

A comparative map of the porcine and human genomes demonstrates ZOO-FISH and gene mapping-based chromosomal homologies.

ZOO-FISH with chromosome-specific DNA libraries (CSLs) from individual flow-sorted human chromosomes was applied on porcine metaphase chromosomes to establish segment homology between the pig and human karyotypes. Forty-seven porcine chromosomal segments corresponding to all human chromosomes except the Y were delineated, resulting in a nearly complete coverage of the porcine karyotype. The syntenic segments detected were further confirmed by the gene mapping information available in the two species. A map demarcating physical boundaries of human homologies on individual pig chromosomes is complemented with a detail survey of the physical and genetic linkage mapping data in the two species. The resultant map, thus, provides a comprehensive and updated comparative status of the human and porcine genomes.

Animals↗

Mapping of bovine FcgammaR (FCGR) genes by sperm typing allows extended use of human map information.

Polymorphic sites within the bovine FcgammaRI (FCGR1), FcgammaRII (FCGR2), and FcgammaRIII (FCGR3) genes were used for proximal mapping of these genes to bovine Chromosome (Chr) 3 (BTA3) with paternal half-sib families from Norwegian Cattle. A fine-structure genetic map of the region was obtained by the analysis of 288 sperm cells from three bulls that were heterozygous for the loci included in the study. No recombinants were observed between FCGR2 and FCGR3 (242 sperm cells). Considering FCGR2 and FCGR3 as a single locus, a three-point linkage analysis for [FCGR2/FCGR3], FCGR1, and INRA003 was carried out. The best-supported order of the loci was found to be INRA003-FCGR1-[FCGR2/FCGR3]. Map distances in a two-point linkage analysis were 10.3 cM between [FCGR2/FCGR3] and FCGR1, and 25.5 cM between FCGR1 and INRA003, respectively. This linkage mapping of the bovine FCGR gene family resembles the human situation where all FCGR genes are located at Chr 1 (HSA1), at position q21-q24. Moreover, the results locate the evolutionary breakpoint between HSA1q and BTA3 within the human 1q24 region.

Alleles↗

Expansion of the pig comparative map by expressed sequence tags (EST) mapping.

We have used a PCR-based approach for the genetical and physical mapping of 34 transcripts isolated from a porcine small intestine cDNA library. All but one gene were regionally localized by using a somatic pig-rodent cell hybrid panel, and 12 genes were mapped by linkage analysis of single-stranded conformational polymorphisms developed in 3' untranslated regions of transcripts. For 20 of the transcripts, the human homolog has already been mapped. This study thus represents a significant contribution to the pig comparative map. Some important findings were that we could clarify the extent of a previously identified inversion event in a region of conserved synteny between SSC6q and HSA1p, that SSC14q does contain a region homologous to HSA1, a situation not clear from earlier ZOO-FISH studies, and that the homology between SSC17 and HSA20 includes the p-arm of HSA20.

Animals↗

An improved linkage map of rat chromosome 3 with three mapping panels.

Our purposes were to develop an improved linkage map for rat Chromosome 3 and to develop new markers polymorphic between Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. The linkage mapping panel consisted of three F2 populations totaling 359 rats. Twenty-five new markers were developed and placed on the linkage map. About half of these markers (13) were polymorphic between S and R rats. The final map spans 124.7 centiMorgans (cM) and includes 64 markers. The average distance between adjacent markers is 1.9 cM, and the largest separation is 10.5 cM.

Animals↗

Restriction map of a 35-kb HLA fragment constructed by nested deletion 'drop-out' mapping.

An efficient method for generating detailed restriction maps of large cloned DNA segments is demonstrated. The mapping strategy entails comparing restriction fragments from a parent clone and from nested deletion derivatives of that clone. In a set of deletion plasmids of decreasing size, an individual fragment will be lost, or 'drop-out', according to its position in the cloned fragment. In this demonstration, nested deletions were generated in both directions in a 35-kb DNA segment from the human leukocyte antigen (HLA) region by intramolecular transposition of an engineered gamma delta (Tn1000) element present in a special 'deletion factory' cloning vector [Wang et al., Proc. Natl. Acad. Sci. USA 90 (1993) 7874-7878]. Fifteen plasmids with deletions extending in one direction and eleven plasmids with deletions extending in the opposite direction were digested singly by each of four restriction enzymes. A total of 36 cleavage sites were mapped in the 35-kb HLA fragment. This drop-out approach using nested deletions provides a simple and efficient means of mapping restriction sites, genes and other features of interest in cosmid-sized cloned DNA segments or DNAs.

Animals↗

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mapping the human liver/islet glucose transporter (GLUT2) gene within a genetic linkage map of chromosome 3q using a (CA)n dinucleotide repeat polymorphism and characterization of the polymorphism in three racial groups.

The human liver/islet glucose transporter (GLUT2), a candidate gene for diabetes, has been incorporated into a genetic linkage map for chromosome 3q using a (CA)n dinucleotide repeat polymorphism adjacent to the 3'-end of exon 4a. We have found a total of nine alleles ranging in length from 153 to 169 nucleotides in three racial groups and have determined the precise structure of the variable region for four of the alleles by DNA sequencing. Five alleles were found to be common to the American Black, Caucasian, and Pima Indian racial groups studied. One allele (169 bp) was unique to American Blacks, and another rare allele (153 bp) was found only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the Caucasian (CEPH) reference pedigree collection is 60%, for American Blacks 71%, and for Pima Indians 53%. An independent study recently identified the same dinucleotide repeat and found six alleles in a Caucasian population (Froguel et al., 1991), a result that we confirm; however, our sequencing data indicate a different molecular structure for the polymorphism for some of the alleles. We have constructed a new genetic linkage map of chromosome 3q uniquely placing the GLUT2 gene between flanking markers D3S26 and D3S43. The genetic map consists of 23 loci (25 RFLPs and 2 (CA)n dinucleotide repeat markers) with 14 markers uniquely localized with odds of at least 1000:1. Three genes (FTHL4, TF, GLUT2) are integrated into the map, which spans a sex-average distance of 147.3 cM, 103.8 cM in males and 227.0 cM in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Refined genetic mapping of a gene for familial juvenile nephronophthisis (NPH1) and physical mapping of linked markers. APN Study Group.

We have recently assigned a gene for familial juvenile nephronophthisis (NPH1) to chromosome 2q between microsatellite markers at loci D2S135 and D2S110. Here we have extended and refined our previous linkage analysis by studying five additional NPH families and by testing five additional markers. By haplotype analysis in a large family yielding proof of linkage, D2S135 and D2S283 were defined with certainty as flanking the NPH1 critical region within a 14-cM interval. These data now allow cytogenetic assignment of the NPH1 critical region to 2q11.1-q21.1. Furthermore, haplotype analysis in 12 small families helped to define as flanking markers D2S293 and D2S363, which span an 8-cM interval. Multipoint linkage analysis by the location score method resulted in a maximum multipoint lod score of 10.30. The Zmax-1 support interval spans 6.9 cM and is flanked by marker loci D2S293 and D2S363. Since IL1A maps to this region and has been cytogenetically mapped to 2q13 in the literature, NPH1 can be assigned more closely to 2q13 or adjacent bands. Contigs of CEPH mega-YAC clones in the region were established by screening the clones with microsatellite markers, adding marker IL1A to the physical map as a novel assignment. We conclude that the NPH1 gene most probably localizes to an interval of 6.9 cM between marker loci D2S293 and D2S363 in the vicinity of 2q13. This contig mapping provides the basis for cloning of this interval and for isolation of the NPH1 gene.

Chromosome Mapping↗

Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury.

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.

Anisotropy↗

Finke's 1792 map of human diseases: the first world disease map?

Documentary evidence reveals that a German physician L.L. Finke produced a world map of diseases in 1792. This is much earlier than any world disease map previously known. Contrary to the contemporary literature in medical cartography this data proves that: (1) It was neither yellow fever nor cholera epidemics but indigenous diseases that were the catalyst for this earlier world disease map. (2) It predates Humboldt's influence on thematic mapping.

Epidemiology↗