My laboratory is interested in the study of nonrandom segregation of chromosomes during meiosis in mammals. This research encompasses the determination of the genetic requirements for nonrandom segregation, the clinical and evolutionary implications of this process, and the use of specific systems to identify at the molecular level genes and cellular structures that are key players in fair and random segregation of chromosomes during meiosis.

We are currently characterizing different aspects of two model systems of nonrandom segregation of chromosomes in mammals. The first system involves the segregation of Robertsonian translocations in both human and mouse. In humans, this system is interesting because Robertsonian translocations are a common and clinically relevant chromosome rearrangement. In the mouse, Robertsonian translocations provide an exciting opportunity to characterize at the genetic level the spindle apparatus of female meiosis. In addition, these studies may have profound consequences in the evolution of the karyotype in mammals and in the functional definition of the centromere. The second system involves nonrandom segregation of chromatids at the second division of female meiosis in the mouse depending of the genotype of the fertilizing sperm. Therefore, this observation violates two basic tenets of Mendelian genetics, random segregation of alleles during meiosis (Medel's law of segregation) and independent segregation of chromosomes during meiosis in one sex with respect to segregation of chromosomes in the other sex. Because males from different inbred strains can be classified into two groups according to their ability to elaborate the nonrandom segregation phenotype, we have been able to show that the phenotype segregates as a single locus with haploid gene action and to define a candidate interval for the relevant locus. Completion of ongoing experiments would reduce the candidate interval to a size suitable for positional cloning. The identification of the gene will provide exciting opportunities regarding its mode of action in normal meiosis and in nonrandom segregation systems.