PubMed Health⌕ Search

Biomedical subjects

L Linton

Publications and source records attributed to L Linton.

9 recordsLinked to original sources
PubMed2001

A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.

We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.

Chromosome Mapping↗
PubMed2000

An SNP map of the human genome generated by reduced representation shotgun sequencing.

Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history. It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases. Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping.

Algorithms↗
PubMed1999

First and second order maternal behavior related afferents of the lateral habenula.

We demonstrated previously that the lateral habenula (Lhb) mediates maternal behavior. Our present goal was to identify the first and second order afferent connections of the Lhb, particularly those relevant for maternal behavior. Using pseudorabies virus (PRV) as a retrograde transneuronal tracer and the retrograde tracer Fluoro-Gold, we identified first order Lhb afferent projections from the lateral preoptic area, bed nucleus of the stria terminalis, nucleus accumbens and ventral tegmental area, each important for the display of maternal behavior. Maternally relevant second order neurons originated from the medial preoptic area and amygdala. Additional regions with first and second order neurons afferent to the Lhb were also identified.

Afferent Pathways↗
PubMed1999

Toward real-world sequencing by microdevice electrophoresis.

We report results using a microdevice for DNA sequencing using samples from chromosome 17, obtained from the Whitehead Institute Center for Genome Research (WICGR) production line. The device had an effective separation distance of 11.5 cm and a lithographically defined injection width of 150 microm. The four-color raw data were processed, base-called by the sequencing software Trout, and compared to the corresponding ABI 377 sequence from WICGR. With a criteria of 99% accuracy, we achieved average continuous reads of 505 bases in 27 min with 3% linear polyacrylamide (LPA) at 150 V/cm, and 460 bases in 22 min with 4% LPA at 200 V/cm at a temperature of 45 degrees C. In the best case, up to 565 bases could be base-called with the same accuracy in <25 min. In some instances, Trout allowed for accurate base-calling down to a resolution R as low as R = 0.35. This may be due in part to the high signal-to-noise ratio of the microdevice. Unlike many results reported on capillary machines, no additional sample cleanup other than ethanol precipitation was required. In addition, DNA fragment biasing (i.e., discrimination against larger fragments) was reduced significantly through the unique sample injection mechanism of the microfabricated device. This led to increased signal strength for long fragments, which is of great importance for the high performance of the microdevice.

Base Sequence↗
PubMed1998

Intact neurons of the lateral habenular nucleus are necessary for the nonhormonal, pup-mediated display of maternal behavior in sensitized virgin female rats.

Our research has demonstrated that the lateral habenular nucleus (Lhb) is necessary for the hormonal onset but not the postpartum maintenance of maternal behavior in the rat (K. P. Corodimas, J. S. Rosenblatt, & J. I. Morrell, 1992; K. P. Corodimas, J. S. Rosenblatt, M. E. Canfield, & J. I. Morell, 1993; T. Matthews-Felton, K. P. Corodimas, J. S. Rosenblatt, & J. I. Morell, 1995). To test the role of the Lhb in the nonhormonal onset of maternal behavior, we used the sensitization model in which the continual exposure of females to pups induces maternal behavior. Ovariectomized females received bilateral cytotoxic lesions of neurons of either the Lhb or the dorsal medial cingulate cortex-hippocampus, or they were unoperated. Maternal behavior, activity, and oromotor carrying capability were tested. Complete lesions of the neurons of the Lhb induced significant deficits in pup retrieval and nest building. Sniffing, licking, and crouching behaviors were unaltered. Activity and carrying ability were normal. These results indicate a role for the Lhb that extends to the nonhormonally dependent onset of maternal behavior, but they also indicate a more limited role than in the mediation of the hormonal onset of the behavior.

Animals↗
PubMed1995

Measuring the psychosocial impact of urinary incontinence: the York Incontinence Perceptions Scale (YIPS).

OBJECTIVE: The York Incontinence Perceptions Scale (YIPS) was developed to measure the psychosocial aspects of urinary incontinence and its management. DESIGN: Testing of internal consistency and validity of the YIPS. SETTING AND PARTICIPANTS: Subjects were 101 female rural community residents (mean age = 67.4 years) diagnosed with urinary incontinence and participating in a 25-week longitudinal randomized control study testing the efficacy of treating incontinence with a behavioral/educational intervention. MEASUREMENTS: Participants completed the YIPS, a bladder chart monitoring daily incontinence episodes, the Aids to Living Scale, the Incontinence Impact Questionnaire, and single-item ratings of self-perceptions of amount of leakage, continence status, and overall health status. MAIN RESULTS: The YIPS had high internal consistency (a = .78). Positive adjustment on the YIPS was correlated with lower frequency of incontinence (r = -.44), and self-ratings of improvement in amount of leakage (r = .60), improved continence status (r = .38), and overall health status (r = .32). At the end of the 25-week treatment period, the participants in the treatment group reported a more positive adjustment on the YIPS than did participants in the control group (t[99] = 4.78, P < .001), which was concordant with a reduction in the incidence of incontinence in the treatment group (F[1,91] = 6.95, P < .01). CONCLUSIONS: The YIPS is a brief, yet reliable, instrument that addresses such psychosocial issues as coping, control, and acceptance of incontinence.

Aged↗
PubMed1991

Testing life-cycle theory by computer simulation--I. Introduction of genetical structure.

Computer simulation was used to relax assumptions of analytical life-cycle theory about the eventual outcome of evolution in a constant environment. The computer simulation models, of diploid one-locus genetic systems, are described in detail. Good agreement was obtained between the analytical and simulation outcomes, except in some cases of discrepancy between the male and female life cycles.

Animals↗
PubMed1991

Testing life-cycle theory by computer simulation--II. Bet-hedging revisited.

Analytical and computer models were used to reexamine bet-hedging, the reduction in fecundity that is evolutionarily advantageous in conditions of greater variation in juvenile survivorship or less variation in adult survivorship. The computer simulation models represent diploid one-locus genetic systems with semidominance. Schaffer's (1974) predictions proved remarkably robust when variations were symmetrical, and a simple modification allowed successful prediction for the asymmetries that occurred in the computer simulations when variations were large.

Animals↗