RESEARCH

ONGOING PROJECTS:

1. How meiotic recombination levels are controlled and the consequences in fertility and evolution:

During the formation of the gametes, the exchange of genetic material that occurs between homologous chromosomes is known as meiotic recombination. Recombination has important implications not only in genetic diversity, but also in fertility. Alterations in the number or distribution of recombination events often result in chromosome missegregation during meiosis, producing gametes that contain extra or miss chromosomes. For instance, trisomy 21 (Down syndrome) is frequently associated with absence of recombination in chromosome 21. At least 10-25% of all human fetuses are chromosomally abnormal, but most do not survive to birth.

Given its impact in human fertility, it is important to understand what determines the amount of recombination. Interestingly, recombination is not simply the result of a stochastic process, but there is a genetic control of the meiotic recombination levels. However, how that control operates remains unknown. Mutations in several genes disrupt the recombination process, but the question about the fine control remains open.

Interestingly, we found an X-linked gene/s involved in the control of genome-wide levels of meiotic recombination in mouse oocytes (1). By genetic, genomic and immunohistochemistry approaches, we aim to identify and characterize this X-linked gene/s that is involved in natural variation in recombination, in order to: a) uncover the mechanisms that control meiotic crossover frequency b) and their evolution; and c) study its role in infertility.

2. How a gene family has evolved and its implications in immunity, fertility and heredity:

Despite the large number of genes described, very little is know about many of them. By comparing the genome sequences of diverse organisms, it is possible to reconstruct their evolutionary history and, in doing so, to obtain clues about their functions, as well as to identify additional genes and pseudogenes.

The Schlafen family of genes is located within the Om region in mouse chromosome 11, and little has been described about them apart from their possible role in the immune system development and response. Interestingly, we also mapped in this region two additional phenotypes: embryonic lethality (2) and unequal segregation of chromatids during meiosis or meiotic drive (3).

In order to understand their role in these interesting phenotypes, we are doing a comparative sequence analysis of this family of genes. We have found that the Schlafen genes were generated by multiple duplications, increasing in copy number since the divergence of mammals, and are conserved in humans. Moreover, they are also present in many poxviruses. Since mouse is a model organism for human disease and fertility, our current studies are aimed to understand the function, regulation and evolution of this gene family and their implications in human health.

(1) De la Casa-Esperon et al. (2002) Genetics 161, 1651-9.
(2) Bell et al. (2006) Genetics 172, 411-23.
(3) Pardo-Manuel de Villena et al. (2000) Genetics 154, 333-342.