Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

The Nepal longitudinal study: predicting myopia from the rate of increase in vitreous chamber depth.

Biometric data on 897 Tibetan children living in Kathmandu, Nepal were collected over the period 1992 to 2000 with regular visits every 2 years. Measurements included cycloplegic autorefraction, A-scan ultrasonography, and video phakometry. Children who had not been studied at least once at age 12 years or older were not included in these analyses. The other subjects were divided into two groups; myopic if the refractive error was ever <-0.50 D, and emmetropic/hyperopic if the refractive error was never <-0.50 D, the nonmyopic group. Using all children who had been examined with four or five observations over time, the change of vitreous chamber depth with age by group was determined using a mixed-model regression method. The increase in vitreous length was 0.070 mm/year for the emmetropic group and 0.165 mm/year for the myopic group, with the differences apparent before the onset of myopia. An independent group of 59 children in whom there were two vitreous chamber depth measures before the age of 12 years and one measure taken after 12 years of age were used to assess the rate of increase in vitreous chamber depth as a predictor of myopia. Two other methods were examined using the independent group; the ratio of axial length to corneal radius of curvature and refractive error at age 10 years. Predictors based on rate of increase in vitreous chamber depth and axial length/corneal radius of curvature had sensitivities of 75% and 45%, respectively, and refractive error at age 10 years as a predictor for those who will not become myopic had a sensitivity of 88%.

Detection of cis-element clusters in higher eukaryotic DNA.

MOTIVATION: Computational prediction and analysis of transcription regulatory regions in DNA sequences has the potential to accelerate greatly our understanding of how cellular processes are controlled. We present a hidden Markov model based method for detecting regulatory regions in DNA sequences, by searching for clusters of cis-elements. RESULTS: When applied to regulatory targets of the transcription factor LSF, this method achieves a sensitivity of 67%, while making one prediction per 33 kb of non-repetitive human genomic sequence. When applied to muscle specific regulatory regions, we obtain a sensitivity and prediction rate that compare favorably with one of the best alternative approaches. Our method, which we call Cister, can be used to predict different varieties of regulatory region by searching for clusters of cis-elements of any type chosen by the user. Cister is simple to use and is available on the web. AVAILABILITY: http://sullivan.bu.edu/~mfrith/cister.shtml. CONTACT: mfrith@bu.edu; zhiping@bu.edu.

Prevalence of myopia in Sherpa and Tibetan children in Nepal.

BACKGROUND: Tibetan and Sherpa children living in Nepal share a common ancestry in Tibet and areas to the north of Nepal, but it is evident that these people experience widely contrasting educational and environmental conditions. The purpose of this study was to compare the prevalence of myopia in children with similar genetic backgrounds but who are exposed to contrasting environments. METHODS: Unaided vision and refractive error was measured in 555 Tibetan children in Kathmandu and 270 Sherpa children in the Solu Khumbu region of Nepal. RESULTS: There were marked differences in vision and the prevalence of myopia in the two groups. Ninety-two percent of the Sherpa children had Snellen vision of 20/22 (0.89) or better compared with 70% of the Tibetan children. The range of refractive errors was -6.50 to +7.00 D for the Tibetan children and -1.00 to +3.50 D for the Sherpa children. The Sherpa children had a prevalence of myopia of 2.9% compared with 21.7% for the Tibetan children. CONCLUSIONS: The prevalence of myopia in Sherpa children is low and their rural lifestyle appears to be relatively unstressed. Tibetan children have a higher prevalence of myopia and more rigorous schooling. We did not establish a causal relationship between myopia and the type of schooling, or the environment in general, but we did demonstrate that a simple, rural lifestyle is at least compatible with a virtual absence of myopia.

Radius of curvature of the posterior surface of the cornea.

The radius of curvature of the posterior surface of the cornea was measured in the vertical meridian for 120 children aged 6 to 17 years, using a Purkinje image method. The mean radius of curvature (+/-SD) was 6.42 +/- 0.31 mm, with a range from 5.62 to 7.22 mm. The ratio of anterior to posterior corneal radius was 1.210 +/- 0.045 or 0.827 +/- 0.029 when expressed as a reciprocal. There was a significant correlation between the anterior and posterior corneal radius (y = 0.798x + 0.228, r2 = 0.45). The study provides data that may be applied to a four-surface schematic eye.

Ocular dimensions and refraction in Tibetan children.

A cross-sectional study of 404 Tibetan children (212 males, 192 females) aged 6 to 16 years was conducted in the Bouda region of Kathmandu, Napal in April, 1992. Examination procedures included retinoscopy (1% cyclopentolate HCl), keratometry A-scan ultrasonography, and video ophthalmophakometry. The mean refractive error was +1.11 D (SD: 0.56 D) at age 6 years decreasing to +0.63 D (SD: 0.34 D) at age 16 years with a prevalence of myopia in this group of 3.9%. Most children examined had low refractive errors, with 95.5% having errors in the range -0.50 to +1.50 D. Crystalline lens power decreased by 2.59 D, with an associated increase in its anterior radius of curvature of 1.98 mm and 0.49 mm in its posterior radius of curvature over the age range studied. Vitreous chamber depth increased by 0.69 mm, but no significant changes were recorded in anterior chamber depth, lens thickness, or corneal curvature. We conclude that the balance between the decrease in crystalline lens power and the increase in vitreous length is the major factor in maintaining the tendency to emmetropia in these children.

Domestic animal rabies control: an overview.

Models for rabies control, particularly in dogs and cats in urban centers in Western nations, have been based on mandatory regular vaccination and restriction of movement of animals, with removal of unrestricted animals. When this three-component approach has been unsuccessful or only temporarily maintained, especially in developing countries, constraints on implementation and maintenance, rather than the model itself, have been blamed. The ecology of the reservoir animals, the relations of dogs and cats to people, and the development of culturally adaptable approaches to rabies control have received little serious attention. As a part of a rabies control pilot program assisted by the World Health Organization, the city of Guayaquil, Ecuador, was chosen as an urban center of high rabies prevalence in animals and high rabies risk in people. The ecology of dogs and cats was investigated, and the findings were applied in developing a model based on community education, annual house-to-house vaccination campaigns, stabilization of the dog and cat populations, limitation of restriction and removal of animals to focal-outbreak control, and environmental measures to promote population control. Initial implementation has been successful, and longitudinal studies are in place to monitor maintenance of control.