Expressed sequence tags from Peromyscus testis and placenta tissue: analysis, annotation, and utility for mapping.

BACKGROUND: Mice of the genus Peromyscus are found in nearly every habitat from Alaska to Central America and from the Atlantic to the Pacific. They provide an evolutionary outgroup to the Mus/Rattus lineage and serve as an intermediary between that lineage and humans. Although Peromyscus has been studied extensively under both field and laboratory conditions, research has been limited by the lack of molecular resources. Genes associated with reproduction typically evolve rapidly and thus are excellent sources of evolutionary information. In this study we describe the generation of two cDNA libraries, one from placenta and one from testis, characterize the resulting ESTs, and describe their utility for mapping the Peromyscus genome. RESULTS: The 5' ends of 1,510 placenta and 4,798 testis clones were sequenced. Low quality sequences were removed and after clustering and contig assembly, 904 unique placenta and 2,002 unique testis sequences remained. Average lengths of placenta and testis ESTs were 711 bp and 826 bp, respectively. Approximately 82% of all ESTs were identified using the BLASTX algorithm to Mus and Rattus, and 34 - 54% of all ESTs could be assigned to a biological process gene ontology category in either Mus or Rattus. Because the Peromyscus genome organization resembles the Rattus genome more closely than Mus we examined the distribution of the Peromyscus ESTs across the rat genome finding markers on all rat chromosomes except the Y. Approximately 40% of all ESTs were specific to only one location in the Mus genome and spanned introns of an appropriate size for sequencing and SNP detection. Of the primers that were tried 54% provided useful assays for genotyping on interspecific backcross and whole-genome radiation hybrid cell panels. CONCLUSION: The 2,906 Peromyscus placenta and testis ESTs described here significantly expands the molecular resources available for the genus. These ESTs allow for specific PCR amplification and broad coverage across the genome, creating an excellent genetic marker resource for the generation of a medium-density genomic map. Thus, this resource will significantly aid research of a genus that is uniquely well-suited to both laboratory and field research.

Prostate cancer in African American men is associated with downregulation of zinc transporters.

In the United States, prostate cancer is the most commonly diagnosed male cancer and the second leading cause of all male cancer deaths. Furthermore, incidence rates are higher in African Americans than in any other racial group. Our laboratory is attempting to decipher the environmental and molecular mechanisms involved in the development of prostate cancer in African Americans. Because Africa is a mineral-rich continent, and the zinc levels in the water and diet are high, it is hypothesized that Africans may have genetically downregulated their zinc absorption capacity; otherwise, they would absorb abnormally high levels of zinc, resulting in various serious neurodegenerative and biochemical disorders. It is therefore possible that people of African origin may have a lower capacity to absorb zinc when compared with other racial groups because of their inherent downregulation of zinc transporters. Extensive research has shown that low serum levels of zinc are associated with the increased incidence of prostate cancer. We have evaluated 58 prostate cancer tissues in 2 major racial groups (30 from whites and 28 from African Americans) for their ability to express 2 major human zinc transporters, hZIP1 and hZIP2. In all 30 prostate cancer specimens obtained from white people, the degree of expression of these 2 zinc receptors was high when compared with age-matched and Gleason score-matched specimens obtained from African American patients. We also found a significant downregulation of these 2 zinc transporters in normal prostate tissues from African American men when compared with age-matched white men. The loss of the unique ability to retain normal intracellular levels of zinc may be an important factor in the development and progression of prostate cancer. Our observation that the uptake of zinc may be different in racial groups is intriguing and relevant. Once these data are confirmed in larger groups, this finding could have significant application as a preventive maneuver for at least for some people. Because dietary zinc supplements are relatively nontoxic, any efficacy trial would be low-risk.