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Mutations in ASPM (abnormal spindle-like microcephaly associated) cause primary microcephaly in humans, a disorder characterized by a major reduction in brain size in the apparent absence of nonneurological anomalies. The function of the Aspm protein in neural progenitor cell expansion, as well as its localization to the mitotic spindle and midbody, suggest that it regulates brain development by a cell division-related mechanism. Furthermore, evidence that positive selection affected ASPM during primate evolution has led to suggestions that such a function changed during primate evolution. Here, we report that in Aspm mutant mice; truncated Aspm proteins similar to those causing microcephaly in humans fail to localize to the midbody during M-phase and cause mild microcephaly. A human ASPM transgene rescues this phenotype but, interestingly, does not cause a gain of function. Strikingly. truncated Aspm proteins also cause a massive loss of germ cells, resulting in a severe reduction in testis and ovary size accompanied by reduced fertility. These germline effects, too, are fully rescued by the human ASPM transgene, indicating that ASPM is functionally similar in mice and humans. Our findings broaden the spectrum of phenotypic effects of ASPM mutations and raise the possibility that positive selection of ASPM during primate evolution reflects its function in the germline. [ABSTRACT FROM AUTHOR]

Aim To investigate patterns of genetic divergence between populations of the fruit bat genus Melonycteris Dobson 1877 in relation to the possible effects on dispersal of the geological history of water barriers within and between northern Melanesian archipelagos. Location The genus is found only in the Bismarck Archipelago and Solomon Islands of northern Melanesia. Methods Up to 935 aligned bases of cytochrome b and cytochrome c oxidase subunit I DNA sequences were determined for specimens of most species and subspecies of Melonycteris. Measures of genetic distance, analysis of molecular variation and phylogenetic investigations (using maximum parsimony, maximum likelihood and Bayesian approaches) were conducted to assess the evolutionary relationships amongst populations. Results The deepest divergences within Melonycteris separate the genus into two reciprocally monophyletic clades from first, the Bismarck Archipelago, and secondly, the Solomon Islands. Within the Solomon Islands, five major clades received strong support. Listed in a generally north-western to south-eastern direction these were: (1) specimens from Choiseul and Santa Isabel; (2) specimens from New Georgia and Kolombangara; (3) specimens from Malaita; (4) specimens from Guadalcanal; and (5) specimens from Makira. Outgroup rooting suggested that the clade from Makira was the most basal within the Solomon Islands, being shown as the sister group to all other Melonycteris from this archipelago. Main conclusions Patterns of genetic variation within Melonycteris were generally consistent, given current knowledge of northern Melanesian geological history, with the hypothesis that the dispersal of these fruit bats is strongly inhibited by water barriers. Within the Solomon Islands the main genetic clades were each restricted to a single island or to a group of islands that are thought to have belonged to larger landmasses (Greater Gatumbangara and Greater Bukida) formed by land bridges during the Pleistocene. The high genetic distance between specimens from the Bismarck Archipelago and from the Solomon Islands reflects the persistently large geographic distance between these archipelagos. The unexpected phylogenetic position of the Makira specimens suggests either that this island was the first colonized by Melonycteris in the Solomon Islands or that this population is the relict of a clade that was previously more widely distributed. [ABSTRACT FROM AUTHOR]

The analysis of the influence of genetic variation on regulation of gene expression at a near-genome-wide level has become the focus of much recent interest. It is widely appreciated that many genes are expressed in a tissue-specific manner and that others are more ubiquitously expressed but relatively little is known about how genetic variation might influence these tissue patterns of gene expression. In this review we discuss what is known about the tissue specificity of the influence of genetic variation and review the challenges that we face in combining hugely parallel, microarray-based gene analysis with equally expensive genetic analysis. We conclude that the available data suggest that genetic variation is essentially tissue specific in its effects upon gene expression and this has important implications for experimental analysis. [ABSTRACT FROM AUTHOR]