There has been much speculation as to what role balancing selection has played in evolution. In an attempt to identify regions, such as HLA, at which polymorphism has been maintained in the human ...population for millions of years, we scanned the human genome for regions of high SNP density. We found 16 regions that, outside of HLA and ABO, are the most highly polymorphic regions yet described; however, evidence for balancing selection at these sites is notably lacking--indeed, whole-genome simulations indicate that our findings are expected under neutrality. We propose that (i) because it is rarely stable, long-term balancing selection is an evolutionary oddity, and (ii) when a balanced polymorphism is ancient in origin, the requirements for detection by means of SNP data alone will rarely be met.
We sequenced 114 genes (for DNA repair, cell cycle arrest, apoptosis, and detoxification)in a mixed human population and observed a sudden increase in the number of functional polymorphisms below a ...minor allele frequency of approximately 6%. Functionality is assessed by considering the ratio in the number of nonsynonymous single nucletide polymorphisms (SNPs)to the number of synonymous or intron SNPs. This ratio is steady from below 1% in frequency-that regime traditionally associated with rare Mendelian diseases-all the way up to about 6% in frequency, after which it falls precipitously. We consider possible explanations for this threshold effect. There are four candidates as follows: (1). deleterious variants that have yet to be purified from the population, (2). balancing selection, in which a selective advantage accrues to the heterozygotes, (3). population-specific functional polymorphisms, and (4). adaptive variants that are accumulating in the population as a response to the dramatic environmental changes of the last 7000 approximately 17000 years.
Minimal introns are not "junk" Yu, Jun; Yang, Zhiyong; Kibukawa, Miho ...
Genome research
12, Številka:
8
Journal Article
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Intron-size distributions for most multicellular (and some unicellular) eukaryotes have a sharp peak at their "minimal intron" size. Across the human population, these minimal introns exhibit an ...abundance of insertion-deletion polymorphisms, the effect of which is to maintain their optimal size. We argue that minimal introns affect function by enhancing the rate at which mRNA is exported from the cell nucleus.
Nucleoporin 155 (
Nup155) is a major component of the nuclear pore complex (NPC) involved in cellular nucleo-cytoplasmic transport. We have acquired the complete sequence and interpreted the genomic ...organization of the
Nup155 orthologos from human (
Homo sapiens) and pufferfish (
Fugu rubripes), which are approximately 80 and 8 kb in length, respectively. The human gene is ubiquitously expressed in many tissues analyzed and has two major transcript variants, resulted from an alternative usage of the 5′ cryptic or consensus splice donor in intron 1 and two polyadenylation signals. We have also cloned DNA complementary to RNAs of the
Nup155 orthologs from
Fugu and mouse. Comparative analysis of the
Nup155 orthologs in many species, including
H. sapiens, Mus musculus, Rattus norvegicus, F. rubripes, Arabidopsis thaliana, Drosophila melanogaster, and
Saccharomyces cerevisiae, has revealed two paralogs in
S. cerevisiae but only a single gene with increasing number of introns in more complex organisms. The amino acid sequences of the
Nup155 orthologos are highly conserved in the evolution of eukaryotes. Different gene orders in the human and
Fugu genomic regions harboring the
Nup155 orthologs advocate cautious interpretation of synteny in comparative genomic analysis even within the vertebrate lineage.
Several major single-nucleotide polymorphism (SNP) discovery projects have been launched recently. The SNP Consortium alone has released 102,719 SNPs (http://snp.cshl.org). More recently, 664,846 ...SNPs based on the clone overlaps from the Human Genome Project were submitted by groups at the Sanger Center and at Washington University. So far, few of these SNPs have been validated. Moreover, validation rates have been derived by resequencing the same DNA samples used for the initial discovery. This approach controls for experimental artefacts in the discovery process, but does not control for the presence of segregating sites with rare alleles. Because such sites comprise most of the sites that vary in the human population, they may represent a significant fraction of all sites detected as `SNPs'. The rare alleles are unlikely to be observed again in a second sample, and therefore these sites will not be useful for genetic studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Full-Malaria/Parasites is a database for transcriptome studies of apicomplexa and other parasites, which is based on our original full-length cDNA sequences and physical cDNA clone resources. In this ...update, the database has been expanded to contain the shogun sequencing for the entire sequences of 14 818 non-redundant full-length cDNA clones from six apicomplexa parasites and 6.8 million of transcription start sites (TSS), both of which had been produced by novel protocols using the oligo-capping method and the Illumina GA sequencer. The former should be the ultimate data for exact annotation of the expressed genes, while the latter should be useful for ultra-deep expression analysis. Furthermore, we have launched Full-Arthropods, a full-length cDNA database for arthropods of medical importance. Full-Arthropods contains 50 343 one-pass sequences, 10 399 shotgun complete sequences and 22.4 million TSS tags in anopheles mosquitoes that transmit malaria, tsetse flies that transmit trypanosomiasis and dust mites that cause allergic dermatitis and bronchial asthma. By providing the largest integrated full-length cDNA data resources in the apicomplexa parasites as well as their vectors, Full-Malaria/Parasites and Full-Arthropods should help combat parasitic diseases. Full-Malaria/Parasites and Full-Arthropods are accessible from http://fullmal.hgc.jp/.
Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for ...efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.
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