Worm Breeder's Gazette 15(1): 67 (October 1, 1997)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
|1||Institute of Zoology, University of Fribourg, Perolles, 1700 Fribourg, Switzerland.|
|2||Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.|
him-6 is necessary for proper chromosome segregation during meiosis. Him-6 animals show an increased nondisjunction frequency for all chromosomes resulting in an elevated number of males in the population and many inviable zygotes due to aneuploidy (1). This is associated with a general reduction in recombination (2,3). Cytological observations revealed a high frequency of unpaired chromosomes in oocytes from both him-6(e1423) and him-6(e1104) homozygotes, with the former showing the more severe phenotype. Taken together with the recombination defective phenotype, these observations suggest that the unpaired chromosomes failed to undergo crossing over and that him-6 acts at meiotic events prior to disjunction, such as crossover formation or pairing. him-6 maps on chromosome IV between unc-22 and unc-30 (1,2,3). Its position on the genetic map was refined using deficiencies, placing it between let-93 and let-99, to the right of unc-22. Thanks to the sequencing data from the genome consortium and the help of Richard Bruskiewich, a candidate gene, coding for a putative DNA helicase, was identified in this interval on the cosmid T04A11. While microinjection transformation with T04A11 has so far failed to rescue the him-6 phenotype, the antisense RNA injection produced a weak, but significant Him phenotype. We obtained a partial cDNA from Y. Kohara and we completed the 5' end of the transcript. The length of the cDNA is 3.1 kb which corresponds to the length of the transcript detected on Northern Blot. The sequence of the open reading frame predicts him-6 to encode a putative DNA helicases related to the E. coli RecQ helicase, with significant homology to the gene product of the human BLM ( Bloom's Syndrome) and the S. pombe rqh1+ gene. RecQ types of helicases are thought to play a role in regulating genetic exchange and maintaining genomic stability. Sequencing of the mutant alleles revealed that e1423 is due to a T to an A transition which gives rise to a stop codon in the helicase domain. The mild allele e1104 shows a G to a Q substitution at a conserved position in the helicase domain. The presence of molecular lesions in the gene further confirms that we have identified the him-6 gene. Work is in progress to study the localisation of the him-6 protein and its role during meiosis. 1. Hodgkin et al., Genetics 91, 67-94, 1979. 2. McKim and Zetka, unpublished results. 3. Zetka and Rose, Genetics 141, 1339-1349, 1995.