9513273 Meneely Recessive mutations in at least two autosomal genes, him-5 and him-8, cause high rates of non-disjunction of the X chromosome. Previous work has shown that him-5 also affects the autosomes, although at a much lower frequency, whereas him-8 affects the X chromosome exclusively. Very few of the known meiotic genes affect only one chromosome, although there is indirect evidence for chromosome-specific meiotic regulation in many organisms including humans. Mutations in both him-S and him-8 alter both the number and the distribution of exchanges on the X chromosome. Thus, by genetic tests, these genes appear to be necessary for the stable synapsis of the X chromosome but not for the initiation of pairing. Both genes have been cloned. The him-8 gene will be characterized in detail by sequencing of wild-type and mutant alleles. The expression of the gene will be examined by RT-PCR at different developmental stages, in both sexes, and in various mutant strains affecting meiosis, germ-line development or both. %%% Meiosis is the process by which eukaryotic organisms reduce their chromosome number in half during gamete formation. Early in meiosis, homologous chromosomes pair stably along their length. This synapsis precedes and is necessary for genetic exchange between the homologues. Failure to synapse or exchange leads to chromosome non-disjunction and loss. Mutations that ease non-disjunction are known in many organisms, including the nematode Caenorhabditis elegans. One goal of this project will be to identify many new mutations affecting X chromosome and autosome disjunction in C. elegans, and to characterize these genetically and cytologically. Among the properties characterized will be which chromosomes, germ-line, and meiotic division are affected. This work will be carried out by senior biology majors working for academic credit. A third project Will use strain polymorphisms and multiplex PCR to quantitate all of the crossovers that occur on the X chromosome during oogenesis in both wild-type and mutant animals. Genetic data and the preliminary data from this analysis indicate that most of the X chromosome exhibits complete interference, such that there is exactly one crossover on the X chromosome during oogenesis. This will be confirmed. ***
