This project has been funded by the Nuffield Foundation, although the views expressed are those of the authors and not necessarily those of the Foundation. The project also received funding from the James S McDonnel Foundation. The authors thank Timothy Myers, Jack Clearman and Swiya Nath for help with data collection. The study described formed part of the PhD thesis of Amy Devine at the University of Cambridge. The authors thank Dr Ann Dowker and Prof. Melissa Hines for feedback on the thesis which informed revisions of this article.
The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.
Chromosome painting was employed to measure frequencies of reciprocal translocations in human lymphocytes induced by 60Co gamma rays, with emphasis on low doses. Translocations and dicentrics were distinguished by use of a pan-centromeric probe. A total of 41,151 metaphases were analyzed at doses below 0.2 Gy. The linear "take-off" slope of the linear-quadratic dose-response curve for translocations, i.e., the alpha coefficient, was measured to be 0.023 +/- 0.005 translocations per cell per Gy. This alpha coefficient is more precise than previously measured. Because the alpha coefficient is the dominant contributor to the translocation frequency induced by low-level exposures, the results presented here will substantially reduce uncertainties in biodosimetry estimates obtained for stable translocations.
Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.
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