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At least 19 recordsLinked to original sources
PubMed1993

A constraint logic programming framework for constructing DNA restriction maps.

Restriction mapping is an important computational problem in molecular biology, particularly in genetic engineering and DNA sequencing. It is different in that it is not only a purely computational problem but involves an interaction between experimental data collection procedures and the mapping algorithms. Consequently, the problem is loosely defined and in practice requires a flexible and versatile algorithm. We describe a framework for solving many restriction mapping problems in the constraint logic programming language CLP (R) which takes advantage of the declarative and powerful features of constraint logic programming. A CLP (R) algorithm is developed for solving a simple restriction mapping problem. The algorithm is the extended to handle more complex variations of restriction mapping such as fragments with errors, circular maps, multiple enzymes and partial digests. The mapping variants are integrated within the same framework and differ in the constraints required to define the kind of map consistency. Various search heuristics and control strategies to improve the search process are also incorporated as constraints.

Algorithms↗
PubMed1996

A nonlinear method for estimating nucleotide polymorphism from restriction maps.

Restriction mapping is used to estimate nucleotide sequence polymorphism when the regions to be studied are too long or too numerous to be sequenced. Restriction mapping is less costly than DNA sequencing, but it does not allow direct measurement of underlying nucleotide polymorphism. It is therefore useful to be able to estimate underlying nucleotide polymorphism from observations of polymorphism in restriction maps, as this offers some of the resolution afforded by DNA sequencing at a reduced cost. Previous estimators of underlying nucleotide polymorphism have assumed that each restriction-enzyme-binding site contains, at most, a single polymorphic nucleotide position (the low-polymorphism-frequency assumption), and this assumption has placed an upper limit on the level of polymorphism that can be resolved by these estimators. The present study documents an estimator which allows relaxation of this assumption. The new estimator more accurately estimates underlying nucleotide polymorphism when the polymorphism level is high enough to falsify the low-polymorphism-frequency assumption. The new estimator therefore yields good results for data sets that are too divergent for analysis by present methods.

Animals↗
PubMed1986

Restriction maps and restriction fragment length polymorphisms of the human 21-hydroxylase genes.

Restriction maps were constructed for the two human 21-hydroxylase genes (21-OHA and 21-OHB) by using DNA from subjects homozygous for a deletion of each gene. Comparing the patterns of these two genes, a KpnI restriction site occurred in the 21-OHA gene in place of a TaqI site in the 21-OHB gene about 1-kb from the 5' end of the gene, and an extra EcoRI site was located 500 bp 5' to the common EcoRI site. The DNA of fourteen unrelated normal subjects was digested with nine restriction endonucleases (AccI, BamHI, BgIII, EcoRI, HindIII, KpnI, MspI, SacI and TaqI). Restriction fragment length polymorphisms were found with EcoRI, HindIII and AccI that resulted from polymorphic endonuclease sites outside the genes.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Characterization of a yeast mitochondrial locus necessary for tRNA biosynthesis. Deletion mapping and restriction mapping studies.

Yeast mitochondrial DNA codes for a complete set of tRNAs. Although most components necessary for the biosynthesis of mitochondrial tRNA are coded by nuclear genes, there is one genetic locus on mitochondrial DNA necessary for the synthesis of mitochondrial tRNAs other than the mitochondrial tRNA genes themselves. Characterization of mutants by deletion mapping and restriction enzyme mapping studies has provided a precise location of this yeast mitochondrial tRNA synthesis locus. Deletion mutants retaining various segments of mitochondrial DNA were examined for their ability to synthesize tRNAs from the genes they retain. A subset of these strains was also tested for the ability to provide the tRNA synthesis function in complementation tests with deletion mutants unable to synthesize mature mitochondrial tRNAs. By correlating the tRNA synthetic ability with the presence or absence of certain wild-type restriction fragments, we have confined the locus to within 780 base pairs of DNA located between the tRNAMetf gene and tRNAPro gene, at 29 units on the wild-type map. Heretofore, no genetic function or gene product had been localized in this area of the yeast mitochondrial genome.

Chromosome Deletion↗
PubMed1994

Restriction mapping of phage lambda vectors using non-radioactive methods.

In order to take advantage of non-radioactive methods, we have developed two plasmids (p lambda LE and p lambda RE) for mapping restriction sites of long inserts cloned in phage lambda vectors. These plasmids are constructed by cloning the left 402-bp and right 560-bp phage lambda genome ends, respectively. To map restriction sites, the cloned sequences in p lambda LE and p lambda RE are labeled with digoxygenin and hybridized to partially digested lambda DNA. The ladder of bands detected with these probes can be used to construct restriction maps in the same way as those obtained using radioactively labeled cos complementary oligodeoxyribonucleotides [Rackwitz et al., Gene 30 (1984) 195-200].

Bacteriophage lambda↗
PubMed1997

Genomics via optical mapping. II: Ordered restriction maps.

In this paper, we describe our algorithmic approach to constructing ordered restriction maps based on the data created from the images of population of individual DNA molecules (clones) digested by restriction enzymes. The goal is to devise map-making algorithms capable of producing high-resolution, high-accuracy maps rapidly and in a scalable manner. The resulting software is a key component of our optical mapping automation tools and has been used routinely to map cosmid, lambda and BAC clones. The experimental results appear highly promising.

Algorithms↗
PubMed1979

Structure of the malB region in Escherichia coli K12. III. Correlation of the genetic map with the restriction map.

A correlation between the genetic and physical maps of the malB region was obtained by performing a restriction cleavage analysis of DNA's carrying various genetically characterized malB deletions. This also allowed to localize the boundaries between malF and malE, malE and malK, mal K and lamB on the restriction map. The genetic map is not grossly distorted with respect to the physical map.

Chromosome Mapping↗
PubMed1991

[Studies on mtDNA of Ustilago maydis. II. Restriction mapping].

A restriction map was constructed for mtDNA of Ustilago maydis. The fragment order for each restriction enzyme was determined by DNA hybridization and fragment overlapping. The restriction sites were located by analysing the secondary digestions of the cloned mtDNA fragments. It was also found that the mtDNA of U. maydis was a circle molecule (60.7 kb), without recognizable repeat sequence.

DNA, Mitochondrial↗
PubMedDate not supplied

The restriction mapping of c gene deletions in Streptomyces bacteriophage phi C31 and their use in cloning vector development.

In addition to 20 previously mapped restriction sites in the DNA of phi C31, we have determined eight sites for SphI, four for EcoRV, and two for SstII; there are none for BglII or SstI. Nine sites were in a 12-kb segment of DNA containing no previously mapped sites. Deletions causing clear-plaque morphology were located in this part of the DNA, in a 3-kb interval between an EcoRV and an SphI site at the centre of the DNA molecule. One of the deletions (delta C3) was obtained in a previously described phi C31c+::vph (viomycin phosphotransferase) derivative containing two PstI sites separated by 3.9-kb of inessential DNA. After in vitro PstI treatment, plaque-forming phages lacking the 3.9-kb fragment were obtained from the c+ phage but not from its delta C3 derivative. Thus a 36.2-kb genome, but not one of 34.4 kb, was able to give infectious virions. PstI-generated DNA fragments of up to 8 kb can be inserted in vitro into the delta C3 derivative with retention of the vph selective marker. With the insertion of a 6.03-kb PstI fragment of plasmid SCP2, the latter phage became a potential vector (with loss of vph) for BamHI-generated DNA fragments of up to 9 kb. In the course of this work, several ClaI sites in phi C31::pBR322 bifunctional replicons were shown to be lost when the DNA was propagated in a dam+ Escherichia coli strain. This will allow the use of such replicons for the cloning of ClaI-generated DNA fragments of up to 6.7 kb.

Bacteriophages↗
PubMed1999

An EM-type Algorithm for Ordered Restriction Map Alignment.

Constructing restriction maps is one of the important steps towards the determination of DNA sequences. Recently, the single-molecule approaches to constructing restriction maps, such as Optical Mapping by D. Schwartz et al., have developed. In practice, with the single-molecule approach like Optical Mapping, the identification of the restriction sites is complicated by several error factors due to resolving power of biological experiments. The ordered restriction map alignment problem is a problem to estimate the actual restriction sites from many imprecise copies of map from single molecule. In this paper, we formulate the problem on the basis of the statistical maximum likelihood estimate, and propose a new efficient local search algorithm for this problem, by applying the Expectation-Maximization (EM) algorithm along with the concept of two-clustering. Our algorithm works well for a lot of sets of simulated data, some of which we believe more difficult than the actual cases.

Journal Article↗
PubMed1996

A yeast artificial chromosome contig and NotI restriction map that spans the tumor suppressor gene(s) locus, 11q22.2-q23.3.

Human chromosome 11q22-q23 is a pathologically important region in which a high level of loss of heterozygosity has been reported for breast, ovary, cervical, colon, and lung carcinomas, malignant melanomas, and hematologic malignancies. This strongly indicates that one or more tumor suppressor genes reside within the deleted region. In this report, we report the development of a contig map that covers most of the deleted regions found in these malignancies. The map comprises a contig of 66 overlapping yeast artificial chromosomes (YACs) and spans a region of 17 Mb from the PGR gene at 11q22.2 to the MLL gene at q23.3. In the process of screening the YACs, 50 new sequence-tagged site markers were developed from the termini of the YAC inserts. These markers were used for chromosome walking, and the data were then integrated into the contig map. NotI restriction mapping of these YACs revealed the presence of at least 26 NotI sites in the region. Using 22 of them, a NotI restriction map of the region from PGR to D11S939 was developed. This YAC contig will provide efficient tools for identification of the putative tumor suppressor gene(s).

Base Sequence↗
PubMed1984

Two-dimensional restriction mapping by digestion with restriction endonucleases of DNA in agarose and polyacrylamide gels.

We have studied with a number of bacterial restriction enzymes the conditions for digestion of DNA in agarose and polyacrylamide gels. The restriction endonucleases HpaII, MspI, HaeIII, HindIII, TaqI, HhaI, AluI, BamHI, EcoRI and SalI are capable of digesting DNA in agarose gels of low electroendosmosis and low sulfate concentration. All enzymes, except BamHI, are also capable of digesting DNA in polyacrylamide gels. With this method, rapid two-dimensional restriction mapping of genomes with low and high sequence complexity is possible.

Animals↗
PubMed1994

On the limitations of automated restriction mapping.

Eight important restriction mapping programs, developed between 1978 and 1993, are analyzed and their performance evaluated. The analyses concentrate on the practical value of the programs to molecular biologists who do restriction mapping on a daily basis, rather than on theoretical efficiency. Although all of the programs could find maps consistent with the data, none were able to discriminate reliably the true map from the other consistent maps, given realistic levels of error. To alleviate this problem, we propose an expert mapping system which utilizes the same inferences and mapping techniques used by expert human mappers to reduce the number of false maps found.

Algorithms↗
PubMed1994

GRAM and genfragII: solving and testing the single-digest, partially ordered restriction map problem.

GRAM (Genomic Restriction map AsseMbly) takes as input single-digest restriction fragments for a set of overlapping clones and outputs one or more plausible partially ordered restriction maps. For each restriction map, GRAM shows the corresponding alignment of the input clone fragments. Due to the error and uncertainty in experimental data, this problem is computationally difficult to solve; therefore, the principle objective in the design of GRAM is to facilitate man-machine collaborative problem solving. GRAM quickly approximates a solution, as follows. (i) A clustering algorithm determines a probable set of restriction fragments. (ii) An assembly algorithm permutes the set of restriction fragments such that the maximal number of clone fragments are contiguous. The output of the GRAM algorithm is displayed for the user to query and edit. This paper describes the stochastic assembly algorithm and shows how it works with the interactive graphics to support man-machine problem solving. In order to test and verify the performance of GRAM, we have developed a program called genfragII to simulate the digestion of clones and fragments; this program is described and results are presented. GRAM is also being used for a number of genome mapping projects.

Algorithms↗
PubMed1995

Phylogeny of Muntiacus (Cervidae) based on mitochondrial DNA restriction maps.

Mitochondrial DNA restriction maps for 12 restriction enzymes of four species of muntjacs--Indian muntjac (M. muntjak), Gongshan muntjac (M. gongshanensis), black muntjac (M. crinifrons), and Chinese muntjac (M. reevesi)--were compared to estimate the phylogenetic relationships among them. Phylogenetic trees were constructed by both distance and parsimony methods. The two resulting trees share a similar topology, which indicates that the black muntjac and the Gongshan muntjac are closely related, followed by the Chinese muntjac; the Indian muntjac is the sister taxon to all the other muntjacs.

Animals↗
PubMed1990

Alignment of Escherichia coli K12 DNA sequences to a genomic restriction map.

We use the extensive published information describing the genome of Escherichia coli and new restriction map alignment software to align DNA sequence, genetic, and physical maps. Restriction map alignment software is used which considers restriction maps as strings analogous to DNA or protein sequences except that two values, enzyme name and DNA base address, are associated with each position on the string. The resulting alignments reveal a nearly linear relationship between the physical and genetic maps of the E. coli chromosome. Physical map comparisons with the 1976, 1980, and 1983 genetic maps demonstrate a better fit with the more recent maps. The results of these alignments are genomic kilobase coordinates, orientation and rank of the alignment that best fits the genetic data. A statistical measure based on extreme value distribution is applied to the alignments. Additional computer analyses allow us to estimate the accuracy of the published E. coli genomic restriction map, simulate rearrangements of the bacterial chromosome, and search for repetitive DNA. The procedures we used are general enough to be applicable to other genome mapping projects.

Amino Acid Sequence↗