Primer3 on the WWW for general users and for biologist programmers.
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Base Sequence↗
Biomedical subjects
S Rozen
Publications and source records attributed to S Rozen.
New techniques for DNA sequence classification.
DNA sequence classification is the activity of determining whether or not an unlabeled sequence S belongs to an existing class C. This paper proposes two new techniques for DNA sequence classification. The first technique works by comparing the unlabeled sequence S with a group of active motifs discovered from the elements of C and by distinction with elements outside of C. The second technique generates and matches gapped fingerprints of S with elements of C. Experimental results obtained by running these algorithms on long and well conserved Alu sequences demonstrate the good performance of the presented methods compared with FASTA. When applied to less conserved and relatively short functional sites such as splice-junctions, a variation of the second technique combining fingerprinting with consensus sequence analysis gives better results than the current classifiers employing text compression and machine learning algorithms.
Algorithms↗
A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.
The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.
Alleles↗
A physical map of 30,000 human genes.
A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.
Animals↗
Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome.
Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.
Algorithms↗
The LabBase system for data management in large scale biology research laboratories.
MOTIVATION: The development of laboratory information management systems (LIMSs) for large scale biology research projects can be a challenging problem. Many such projects generate complex datasets via complex procedures that undergo continuous refinement. A key software challenge is to simplify the database-development task so that databases can be built and modified quickly enough to keep pace with changing project-requirements. RESULTS: LabBase extends the facilities offered by relational database systems to simplify the task of creating databases for large scale biology research projects. LabBase provides a structural object data model, similar to ACEDB, and adds to this the concepts of Materials, Steps, and States: Materials are objects representing the identifiable things that participate in a laboratory protocol; Steps are objects reporting the results of a laboratory or analytical procedure; and States are objects denoting places in a laboratory protocol. The system provides a data definition language for succinctly defining laboratory databases, and operations for conveniently storing and retrieving data in such databases. The system also provides support for workflow management. LabBase is implemented in Perl5 and provides a natural interface for laboratory application programs written in Perl. AVAILABILITY: The software is freely available. Contact the authors. CONTACT: nat@jax.org
Computational Biology↗
A map of 75 human ribosomal protein genes.
We mapped 75 genes that collectively encode >90% of the proteins found in human ribosomes. Because localization of ribosomal protein genes (rp genes) is complicated by the existence of processed pseudogenes, multiple strategies were devised to identify PCR-detectable sequence-tagged sites (STSs) at introns. In some cases we exploited specific, pre-existing information about the intron/exon structure of a given human rp gene or its homolog in another vertebrate. When such information was unavailable, selection of PCR primer pairs was guided by general insights gleaned from analysis of all mammalian rp genes whose intron/exon structures have been published. For many genes, PCR amplification of introns was facilitated by use of YAC pool DNAs rather than total human genomic DNA as templates. We then assigned the rp gene STSs to individual human chromosomes by typing human-rodent hybrid cell lines. The genes were placed more precisely on the physical map of the human genome by typing of radiation hybrids or screening YAC libraries. Fifty-one previously unmapped rp genes were localized, and 24 previously reported rp gene localizations were confirmed, refined, or corrected. Though functionally related and coordinately expressed, the 75 mapped genes are widely dispersed: Both sex chromosomes and at least 20 of the 22 autosomes carry one or more rp genes. Chromosome 19, known to have a high gene density, contains an unusually large number of rp genes (12). This map provides a foundation for the study of the possible roles of ribosomal protein deficiencies in chromosomal and Mendelian disorders.
Animals↗
The LabFlow system for workflow management in large scale biology research laboratories.
LabFlow is a workflow management system designed for large scale biology research laboratories. It provides a workflow model in which objects flow from task to task under programmatic control. The model supports parallelism, meaning that an object can flow down several paths simultaneously, and sub-workflows which can be invoked subroutine-style from a task. The system allocates tasks to Unix processes to achieve requisite levels of multiprocessing. The system uses the LabBase data management system to store workflow-state and laboratory results. LabFlow provides a Per15 object-oriented framework for defining workflows, and an engine for executing these. The software is freely available.
Artificial Intelligence↗
A gene map of the human genome.
The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.
Amino Acid Sequence↗
Genome maps 7. The human transcript map. Wall chart.
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Chromosome Mapping↗
The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned.
It is widely believed that most or all Y-chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y-chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (> 99% identical in DNA sequence) clustered in the AZF region and a functional DAZ homologue (DAZH) on human chromosome 3. The entire gene family appears to be expressed in germ cells. Sequence analysis indicates that the Y-chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene. These results challenge prevailing views of sex chromosome evolution, suggesting that acquisition of autosomal fertility genes is an important process in Y chromosome evolution.
Amino Acid Sequence↗
An STS-based map of the human genome.
A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.
Animals↗
Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene.
We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single-copy gene, DAZ (Deleted in AZoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.
Amino Acid Sequence↗
Eosinophilic pleural effusion in cutaneous myiasis.
We have reported the case of a 54-year-old man with recurrent painful migratory subcutaneous nodules associated with marked blood eosinophilia and an eosinophilic pleural effusion. The entire syndrome was subsequently determined to be due to cutaneous myiasis caused by the larvae of Hypoderma lineatum, the cattle botfly. Infestation by this or other dipterous fly larvae should be among the parasitic diseases considered in the differential diagnosis of any patient with similar symptoms.
Diagnosis, Differential↗
Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin.
The family history of colon cancer was investigated in 38,823 individuals (2,129 families) who comprised a control and an oncology patient series from Tel-Aviv and nearby areas. A significant increased risk for colon cancer was observed among first-degree relatives of colon cancer patients when compared to controls. When the patient sample was divided into two groups based on country and continent of birth--European (Ashkenazim) and other (nonAshkenazim)--the relatives of the nonAshkenazi subjects showed a greater relative risk for colon cancer (P less than 0.05). Colon cancer was found to be less frequent in nonAshkenazim than in Ashkenazim controls. These findings suggest that although the colon cancer frequency in the nonAshkenazi group is lower, the genetic component may be more important than for the Ashkenazi sample. The nonAshkenazi Jews may represent distinct subgroups that differ with respect to either primary genetic susceptibility to colorectal cancer and/or they may have been subjected to peculiar, environmental carcinogenic exposures when compared to their Ashkenazim brethren.
Adult↗
Marfanoid hypermobility syndrome associated with Duane's retraction syndrome.
Marfanoid hypermobility syndrome together with Duane's retraction syndrome in two sisters is presented. To our knowledge, this is the first report of such a combination. A possible mode of inheritance is suggested.
Child↗
Letter: Fluorination of saturated carbon. 2. Direct fluorination of steroids.
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Indicators and Reagents↗
Malignant myelosclerosis.
Malignant myelosclerosis, as described by Lewis and Szur, is characterized by an acute, rapidly fatal illness, with anemia, leukopenia, thrombocytopenia, myeloblasts in the blood, and a "dry tap" on bone marrow aspiration. This entity has been only rarely reported in the American literature. We report three additional cases of myelosclerosis. The patients were 70, 37, and 46 years old with a survival of eight weeks, six weeks, and 11 months, respectively. Bone marrow biopsy specimen showed fibrosis in tow with increased reticulum fibers and blast cells in all. At autopsy, the spleen and liver wereinfiltrated with leukemic cells. In two cases, the lymph nodes were involved. Extramedullary erythropoiesis was also seen. We believe that malignant myelosclerosis is best interpreted as an acute myeloproliferative disorder sharing features with acute leukemia and agnogenic myeloid metaplasia.
Adult↗