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.

Characterization of him-6, a gene required for the proper disjunction of chromosomes during meiosis

Chantal Wicky1, Ann Rose2, Fritz Mueller1

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.