The first genome from the third domain of life.
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Biological Transport↗
Biomedical subjects
O White
Publications and source records attributed to O White.
Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii.
The complete 1.66-megabase pair genome sequence of an autotrophic archaeon, Methanococcus jannaschii, and its 58- and 16-kilobase pair extrachromosomal elements have been determined by whole-genome random sequencing. A total of 1738 predicted protein-coding genes were identified; however, only a minority of these (38 percent) could be assigned a putative cellular role with high confidence. Although the majority of genes related to energy production, cell division, and metabolism in M. jannaschii are most similar to those found in Bacteria, most of the genes involved in transcription, translation, and replication in M. jannaschii are more similar to those found in Eukaryotes.
Amino Acid Sequence↗
TDB: new databases for biological discovery.
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Animals↗
The minimal gene complement of Mycoplasma genitalium.
The complete nucleotide sequence (580,070 base pairs) of the Mycoplasma genitalium genome, the smallest known genome of any free-living organism, has been determined by whole-genome random sequencing and assembly. A total of only 470 predicted coding regions were identified that include genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. Comparison of this genome to that of Haemophilus influenzae suggests that differences in genome content are reflected as profound differences in physiology and metabolic capacity between these two organisms.
Antigenic Variation↗
Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence.
In an effort to identify new genes and analyse their expression patterns, 174,472 partial complementary DNA sequences (expressed sequence tags (ESTs)), totalling more than 52 million nucleotides of human DNA sequence, have been generated from 300 cDNA libraries constructed from 37 distinct organs and tissues. These ESTs have been combined with an additional 118,406 ESTs from the database dbEST, for a total of 83 million nucleotides, and treated as a shotgun sequence assembly project. The assembly process yielded 29,599 distinct tentative human consensus (THC) sequences and 58,384 non-overlapping ESTs. Of these 87,983 distinct sequences, 10,214 further characterize previously known genes based on statistically significant similarity to sequences in the available databases; the remainder identify previously unknown genes. Thirty tissues were sampled by over 1,000 ESTs each; only eight genes were matched by ESTs from all 30 tissues, and 227 genes were represented in 20 or more of the tissues sampled with more than 1,000 ESTs. Approximately 40% of identified human genes appear to be associated with basic energy metabolism, cell structure, homeostasis and cell division, 22% with RNA and protein synthesis and processing, and 12% with cell signalling and communication.
Adult↗
Whole-genome random sequencing and assembly of Haemophilus influenzae Rd.
An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.
Bacterial Proteins↗
A rapid retrieval tool for operating on large, flat archive files.
Computer-aided sequencing and analysis facilities need to efficiently search flat archive files. Retrieval by e-mail or network server connections can become impractical in cases where large numbers of selected entries need to be accessed. Public versions of these archives can be retrieved via ftp and installed on a local hard disk as an alternative to network-based retrieval. After installation, a scheme is required for rapid access of the archive that is consistent with the other production needs of the sequencing facility. We have developed a retrieval system for entries inside a flat-file database. The system works for any flat-file database system such as those used in the public DNA and protein archives.
Animals↗
How many genes in the human genome?
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Genes↗
A quality control algorithm for DNA sequencing projects.
Heterologous DNA sequences from rearrangements with the genomes of host cells, genomic fragments from hybrid cells, or impure tissue sources can threaten the purity of libraries that are derived from RNA or DNA. Hybridization methods can only detect contaminants from known or suspected heterologous sources, and whole library screening is technically very difficult. Detection of contaminating heterologous clones by sequence alignment is only possible when related sequences are present in a known database. We have developed a statistical test to identify heterologous sequences that is based on the differences in hexamer composition of DNA from different organisms. This test does not require that sequences similar to potential heterologous contaminants are present in the database, and can in principle detect contamination by previously unknown organisms. We have applied this test to the major public expressed sequence tag (EST) data sets to evaluate its utility as a quality control measure and a peer evaluation tool. There is detectable heterogeneity in most human and C.elegans EST data sets but it is not apparently associated with cross-species contamination. However, there is direct evidence for both yeast and bacterial sequence contamination in some public database sequences annotated as human. Results obtained with the hexamer test have been confirmed with similarity searches using sequences from the relevant data sets.
Algorithms↗
Splicing signals in Drosophila: intron size, information content, and consensus sequences.
A database of 209 Drosophila introns was extracted from Genbank (release number 64.0) and examined by a number of methods in order to characterize features that might serve as signals for messenger RNA splicing. A tight distribution of sizes was observed: while the smallest introns in the database are 51 nucleotides, more than half are less than 80 nucleotides in length, and most of these have lengths in the range of 59-67 nucleotides. Drosophila splice sites found in large and small introns differ in only minor ways from each other and from those found in vertebrate introns. However, larger introns have greater pyrimidine-richness in the region between 11 and 21 nucleotides upstream of 3' splice sites. The Drosophila branchpoint consensus matrix resembles C T A A T (in which branch formation occurs at the underlined A), and differs from the corresponding mammalian signal in the absence of G at the position immediately preceding the branchpoint. The distribution of occurrences of this sequence suggests a minimum distance between 5' splice sites and branchpoints of about 38 nucleotides, and a minimum distance between 3' splice sites and branchpoints of 15 nucleotides. The methods we have used detect no information in exon sequences other than in the few nucleotides immediately adjacent to the splice sites. However, Drosophila resembles many other species in that there is a discontinuity in A + T content between exons and introns, which are A + T rich.
Animals↗
Information contents and dinucleotide compositions of plant intron sequences vary with evolutionary origin.
The DNA sequence composition of 526 dicot and 345 monocot intron sequences have been characterized using computational methods. Splice site information content and bulk intron and exon dinucleotide composition were determined. Positions 4 and 5 of 5' splice sites contain different statistically significant levels of information in the two groups. Basal levels of information in introns are higher in dicots than in monocots. Two dinucleotide groups, WW (AA, AU, UA, UU) and SS (CC, CG, GC, GG) have significantly different frequencies in exons and introns of the two plant groups. These results suggest that the mechanisms of splice-site recognition and binding may differ between dicot and monocot plants.
Base Composition↗
Familial dystonic choreoathetosis with myokymia; a sleep responsive disorder.
A family is presented with paroxysmal dystonic choreoathetosis transmitted as a dominant trait over five generations. The family is unusual in the marked responsiveness of the episodes to short periods of sleep in several members, in the very variable age of onset, and in the association with prominent myokymia in some cases. These overlap features suggest a link between paroxysmal dystonic choreoathetosis and familial paroxysmal ataxia with myokymia.
Adolescent↗
Spasticity in spinal cord injured persons: quantitative effects of baclofen and placebo treatments.
Spasticity commonly occurs after a spinal cord injury and is characterized by increased resistance to passive movement of peripheral joints. This study examined the effect of an antispasticity medication on stiffness from the myotatic reflex response generated by passive sinusoidal ankle motion. A repeated measures, multiple base-line, single-subject, double-blind design was employed. The independent variable was spasticity medication treatment, where the levels were 40 mg/day and 80 mg/day of baclofen v placebo treatment. Viscous and elastic stiffness measurements were taken at the ankle joint during a placebo base-line phase and during treatment with baclofen for five adult males with traumatic spinal cord injuries. Ankle sinusoidal oscillation frequencies were from 3 to 12 Hz during test sessions. Mean viscous and elastic stiffness scores for all frequencies were calculated for each phase of the study. Randomization tests of mean changes in stiffness measurements between each treatment phase of the study failed to provide any convincing evidence of a significant treatment effect for reduction of spasticity in the traumatic spinal cord injured subjects studied. Further testing is needed to exclude potential confounding factors before this conclusion can be confirmed. The results suggest that baclofen is not a universal treatment of choice for all individuals with spasticity resulting from traumatic spinal cord injury.
Adult↗
Chromosomal aberrations and sister-chromatid exchanges in lymphocytes from coke oven workers.
To test whether coke oven workers, an occupational group known to be at increased cancer risk, manifest increased peripheral blood chromosomal aberration frequencies, we obtained samples from a group of 30 steelworker volunteers, who had worked several years at coke oven jobs. Exposure estimates were made using measurements of work place atmospheric coal tar pitch volatiles and work histories. No statistically significant positive regression of chromosomal aberrations on exposure estimates was found. The data from the coke oven workers were also compared with the obtained concurrently and employing precisely the same laboratory protocol from a group of male Brookhaven National Laboratory employees. The coke oven workers as a group were found to have statistically significantly elevated frequencies of chromatid aberrations and of sister-chromatid exchanges.
Aneuploidy↗
Standardization and analysis of digitized photographic data in the longitudinal documentation of cataractous growth.
Age-related cataract formation in man can be documented with slit and retroillumination photographs. With digitization and image analysis of such photographs a cataract may be characterized by a frequency distribution of picture elements over a 255 step gray scale spectrum. Transition from a clear to a cataractous lens may be manifested as a change from a unimodal, Gaussian to a multimodal, non Gaussian frequency distribution respectively. How should one compare and contrast these two distributions, so to accurately describe the extent and significance of a change in lens opacification? The in vitro system of cold cataract formation in the rabbit lens was used as a model of the much slower process of age-related cataract formation in man. As in the human lens undergoing progressive opacification, the frequency distribution (number of pixels vs. intensity of gray) for a digitized image of a clear lens at 26 degrees C is unimodal and Gaussian; that of a fully developed cold cataract at 10 degrees C is multimodal and non-gaussian. In spite of the increasing multimodality of the frequency distribution as the temperature dropped and the cataract grew in density and size, the mean gray density proved to be a valid and useful measure to characterize the distribution and to compare different unaligned images. The Wilcoxon Rank Sum Test proved to be useless in comparing the frequency distributions from cataract images because it proved to be too sensitive to subtle changes in the degree of opacification. Anomalous behavior of the opacification process--i.e. clarification as well as opacification of the lens during cold cataract formation caused all pairs to appear statistically significantly different when in appearance there was no difference. The mean of the frequency distribution is less sensitive to this anomalous behavior and is useful as a comparative index. The method of calculating the threshold of significant change in the mean density of a cataract image is presented.
Animals↗
Topographic correspondence between total and non-freezable water content and the appearance of cataract in human lenses.
Eight intracapsular and 18 extracapsular human surgical specimens were stereophotographed. Each lens was divided into 10 areas, separating those which appeared transparent from those that showed opacities. Samples weighing 6-12 mg from each area were investigated. The total water content was determined by thermogravimetric analysis; the freezable water content was measured by differential scanning calorimetry. The difference between the two provided the non-freezable water content. Graphic presentation illustrates the correspondence of high total water, low non-freezable water content with location of the turbidity in the lens. Pairwise, statistical comparison shows that in intracapsular human surgical specimens the non-freezable water content in the clear areas of both cortex and nucleus was significantly greater than in the opaque areas.
Body Water↗
Freezable and non-freezable water content of cataractous human lenses.
Twenty-nine cataractous human lenses between the ages of 36 and 93 were investigated. The total water content of cortex and nucleus were obtained by vacuum dehydration. The freezable water content was measured by differential scanning calorimetry. The non-freezable water content was obtained by difference. To measure the extent that syneresis contributes to cataract formation, an excess function was designed. The excess function represents the changes that occur, for example, in non-freezable water content due to cataractogenesis. It is calculated as the difference between the non-freezable water content of a normal lens and that of a cataractous lens of the same age. On the average, there is 7% less non-freezable water in the cortex of a cataractous lens than in the cortex of a normal lens. The corresponding number for the nucleus is 9%. This represents 29 and 36% changes, respectively, in the cortex and nucleus due to syneresis during cataractogenesis.
Adult↗
Validity and reproducibility of the Cooperative Cataract Research Group (CCRG) cataract classification system.
The validity and reproducibility with which six classifiers [one experienced (L.T.C.), and five novices (W.G., F.G., W.W., J.W. and O.W.)] used the CCRG cataract classification system was assessed. The validity of index classifications was assessed by computing sensitivities and pairwise interclass correlations between experienced and novice classifiers using the former's classification as the standard. The number of unordered combinations of terms in the CCRG's classification was reduced by combining cortical terms according to the CCRG's accepted system of staged simplification. The number of combinations of terms at each stage is as follows: Stage I (greater than 1000); II (127); III (63); IV (15); V (7); VI and VII (3) and VIII (2). Excellent agreement was obtained between the experienced and novice classifiers for Stages VII and VIII of the classification, good agreement for Stages V and VI and poor agreement for Stages IV, III and II (sensitivities of 97, 96, 72, 59, 40, 24 and 20% respectively). Good agreement was also achieved for the classifications of single lenticular regions, except for subcapsular regions. The intra- and interobserver reproducibility was assessed by computing the Kappa statistic to (1) compare classifications between novice observers and (2) compare repeat classifications made by the same observer by viewing the same cataract once on each of three different days. The novice classifiers had excellent intraobserver reproducibility for Stages VII and VIII (Kappas of 0.87 and 0.97 respectively), good reproducibility for Stages IV, V and VI (Kappas of 0.53, 0.62 and 0.62, respectively) and marginal reproducibility for stages II and III (Kappas of 0.39 and 0.40, respectively). The intraobserver reproducibility of the experienced classifier was superior to the others for virtually all characteristics with excellent reproducibility for Stages IV, V, VI, VII and VIII with Kappas of 0.79, 0.90, 1.0, 1.0 and 1.0, respectively and good reproducibility for Stages II and III (Kappas of 0.55 and 0.64, respectively). These results indicate that the simplified CCRG cataract classification system (Stages IV-VIII) passes the minimum standards for reproducibility. The performance of the experienced classifier far exceeds the minimum standards and indicates the feasibility of improving classifier performance with training and practice.
Cataract↗