Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait.

An empirical test for branch-specific positive selection.

The use of phylogenetic analysis to predict positive selection specific to human genes is complicated by the very close evolutionary relationship with our nearest extant primate relatives, chimpanzees. To assess the power and limitations inherent in use of maximum-likelihood (ML) analysis of codon substitution patterns in such recently diverged species, a series of simulations was performed to assess the impact of several parameters of the evolutionary model on prediction of human-specific positive selection, including branch length and d(N)/d(S) ratio. Parameters were varied across a range of values observed in alignments of 175 transcription factor (TF) genes that were sequenced in 12 primate species.

Human PAML browser: a database of positive selection on human genes using phylogenetic methods.

With the recent increase in the number of mammalian genomes being sequenced, large-scale genome scans for human-specific positive selection are now possible. Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species. Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage.

A catalog of nonsynonymous polymorphism on mouse chromosome 16.

Numerous phenotypic traits differ among inbred mice, and the genetic diversity of inbred strains has been exploited in studies of quantitative trait loci (QTL). Sequencing the mouse genome has resulted in improved tools for the study of QTL, but a comprehensive catalog of sequence variants between strains would be of great value in identifying and testing potentially causative alleles. A/J DNA was included in the Celera shotgun sequence of the mouse genome and C57BL/6 DNA was sequenced by an international consortium.