Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. The genome of S. mutans UA159, a serotype c strain, has been completely sequenced and is composed of 2,030,936 base pairs. It contains 1,963 ORFs, 63% of which have been assigned putative functions. The genome analysis provides further insight into how S. mutans has adapted to surviving the oral environment through resource acquisition, defense against host factors, and use of gene products that maintain its niche against microbial competitors. S. mutans metabolizes a wide variety of carbohydrates via nonoxidative pathways, and all of these pathways have been identified, along with the associated transport systems whose genes account for almost 15% of the genome. Virulence genes associated with extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains all of the genes essential for competence and quorum sensing. Mobile genetic elements in the form of IS elements and transposons are prominent in the genome and include a previously uncharacterized conjugative transposon and a composite transposon containing genes for the synthesis of antibiotics of the gramicidin͞bacitracin family; however, no bacteriophage genomes are present.

The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately onethird of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulenceassociated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial ''molecular mimicry'' of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.

We present an expanded data set of 50 unlinked autosomal noncoding regions, resequenced in samples of Hausa from Cameroon, Italians, and Chinese. We use these data to make inferences about human demographic history by using a technique that combines multiple aspects of genetic data, including levels of polymorphism, the allele frequency spectrum, and linkage disequilibrium. We explore an extensive range of demographic parameters and demonstrate that our method of combining multiple aspects of the data results in a significant reduction of the compatible parameter space. In agreement with previous reports, we find that the Hausa data are compatible with demographic equilibrium as well as a set of recent population expansion models. In contrast to the Hausa, when multiple aspects of the data are considered jointly, the non-Africans depart from an equilibrium model of constant population size and are compatible with a range of simple bottleneck models, including a 50 -90% reduction in effective population size occurring some time after the appearance of modern humans in Africa 160,000 -120,000 years ago.bottlenecks ͉ combining P values ͉ human demographic inference ͉ population growth E lucidating how and when populations change in size is an important element in reconstructing evolutionary history because these changes often reflect crucial events in the history of a species, such as range expansions, environmental changes, and mixture between groups (1). In addition, making inferences based on population variation data typically requires the specification of a demographic model. Such applications include detecting the signature of natural selection or estimating recombination rates from patterns of linkage disequilibrium (LD) (2-5). Finally, better knowledge of demographic histories in human populations is particularly important for whole-genome, LD-based association studies (6, 7).Motivated by the excess of rare variants observed in mitochondrial DNA data, attention initially focused on models of ancient population growth and on the idea that population expansions may have accompanied the dispersal out of Africa or the emergence of new tool technology in the Upper Paleolithic (8-13). However, the accumulation of nuclear sequence variation surveys showed that this simple growth model was consistent with the observed frequency spectrum only for a subset of the loci (14-16). Likewise, LD surveys revealed marked differences in the rate of LD decay in African populations compared with that in non-African populations (17)(18)(19). These results together with the higher levels of sequence variation in African populations compared with that in non-African populations led to the proposal that population size reduction, such as bottlenecks, account for patterns of variation and LD in non-African populations (15,18,19). This bottleneck was hypothesized to correspond with the dispersal of modern humans out of Africa (18).However, the investigation of formal bottleneck models has typically used a single aspect of genetic var...

An overall burden of rare structural genomic variants has not been reported in bipolar disorder (BD), although there have been reports of cases with microduplication and microdeletion. Here, we present a genome-wide copy number variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single nucleotide polymorphism (SNP) 6.0 SNP and CNV platform. Singleton deletions (deletions that appear only once in the dataset) more than 100 kb in length are present in 16.2% of BD cases in contrast to 12.3% of controls (permutation P = 0.007). This effect was more pronounced for age at onset of mania p18 years old. Our results strongly suggest that BD can result from the effects of multiple rare structural variants.

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