Nature Genetics pp 278 - 280 and pp 219 - 220

Men have traditionally been portrayed as the great travellers and explorers, migrating to distant lands to conquer, settle and procreate. Mark Seielstad, of Harvard University, and colleagues now present data suggesting that women's movements have played a more important role in distributing genes than previously realized. They compared the variation in DNA sequences on the Y chromosome, which pass from male to male through the generations, with that of mitochondrial DNA, which is transmitted exclusively by females. A comparison of these genetic sequences between geographically distant populations revealed that mitochrondrial DNA is more similar between populations than the Y chromosome, indicating that, throughout history, women have travelled further and more often than men. Their higher migration rate may be explained in part by 'patrilocality', where women move to the domicile of their mates. However, as highlighted by Mark Stoneking, of Pennsylvania State University, in an accompanying News & Views article, patrilocality tends to operate on a local scale and may not explain the continental or global patterns identified in the study. It appears that women have been more active in human migration than previously given credit.

Nature Genetics pp 228 - 230

Diethylstilbestrol (DES) was prescribed to prevent miscarriage in the USA for a period of almost 25 years (which ended in 1971). Approximately 1 million women were exposed to DES while in the womb. Some of these women developed abnormalities of the reproductive tract, experienced infertility problems and developed cancer of the vagina and cervix at an early age. The precise mechanism by which DES elicits its effects remains unknown. David Sassoon, of The Mount Sinai School of Medicine, and colleagues now report that the Wnt7a gene may be a key molecular target of DES. They observed that female mice lacking Wnt7a have similar reproductive tract abnormalities to mice prenatally exposed to DES. In addition, the levels of Wnt7a are dramatically reduced in the uteri of DES-exposed mouse embryos during a critical period in reproductive tract development. The researchers propose that DES causes a reduction in Wnt7a expression during this crucial time, leading to the complications experienced by some of the 'DES daughters'. These findings -- as well as a recent report that tamoxifen, a DES-like substance used in the treatment of breast cancer, is associated with a twofold increase in uterine cancer -- underscore the importance of understanding the molecular responses to drugs when evaluating their clinical applications.

Nature Genetics pp 239 - 243, pp 244 - 250 and pp 222 - 223

One could be forgiven for thinking that fish are better suited to hollandaise sauce and a nice bottle of Chardonnay than as a powerful tool for investigating gene function. Two reports in this issue, however, exemplify how fish are becoming 'le plat du jour' for human geneticists. Two research teams, led by Leonard Zon, of Harvard Medical School, and Shuo Lin, of Medical College of Georgia, have characterized two zebrafish mutants with blood disorders. sauternes mutants (named after their pale blood colour) suffer from hypochromic anaemia (a condition in which the red blood cells have a reduced volume and haemoglobin content) which is caused by a mutation in the alas2 gene. yquem mutants have blood cells that are extremely sensitive to light, a condition reminiscent of human porphyria, which is associated with light-sensitive dermatitis. The mutants have a defective copy of the urod gene, which, like alas2, encodes an enzyme involved in haem biosynthesis. Both mutant zebrafish strains exhibit features similar to those observed in human patients with inherited blood diseases and represent the first genetic animal models of these inborn errors of metabolism. Furthermore, they are the first fish models of any human disease.

Large-scale generation of zebrafish mutants -- which has been possible because the fish are small and easy to keep, have a short generation time and many offspring -- have generated a wealth of mutants. Many of these may prove useful human disease models and experimental systems for testing gene therapy strategies. In an accompanying News & Views article, Chris Amemiya, of Boston University School of Medicine, discusses the advantages, as well as the current limitations, of the zebrafish as a 'tool' for dissecting gene function.