The Natural History of SNPs and Mutations
The presence of heterozygous 'Mendelian mutations' in general populations illustrates the point that it may not always be helpful to rigidly separate polymorphism and mutation data. Another factor which argues against division of these data is that both SNPs and mutations arise by the same mechanism, although selection may influence their spread in populations. Miller and Kwok 2001 presented a detailed review of the 'life cycle' of a single nucleotide variation, they defined SNP and mutation...
ORNL Genome Channel GC
The ORNL Oak Ridge National Laboratory Genome Channel GC http compbio.ornl. gov channel consists of a series of tools for visualizing and querying the NCBI human genome sequences and those of other organisms assembled and annotated by ORNL and collaborators. The GC browser provides the usual categories of nucleotide-level annotation repetitive sequences, CpG islands, polyA sites and marker positions. The GC gene prediction protocol is pitched somewhere between Ensembl and HGB GrailEXP...
Searching The Internet For Genetic Information
The World Wide Web began as an information-sharing and retrieval project at the European particle physics laboratory CERN Berners-Lee et al., 1999 . It has only recently evolved into the mass media beast that we all know. But just as the internet began, so it continues as an information-sharing resource for scientists in all fields. One cannot deny that commercial proliferation has not been an unmitigated success for the growth of the web but this has led many scientists to perceive the...
ENU Mutagenesis Centres
Several public large-scale ENU mutagenesis projects are already underway and are providing new models for the study of disease and gene function to the community Brown and Nolan, 1998 De Angelis et al, 2000 Justice et al, 1999 Nolan et al., 2000 Table 6.1 . Some of the mutagenesis centres are working in several disease areas to identify new mutants including the ENU Mutagen-esis Programme at Harwell the RIKEN Mouse Functional Genomics Group http www.gsc.riken.go.jp Mouse , and the GSF ENU Mouse...
Single Nucleotide Variation SNPs and Mutations
Terminology for variation at a single nucleotide position is defined by allele frequency. In the strictest sense, a single base change, occurring in a population at a frequency of gt 1 is termed a single nucleotide polymorphism SNP . When a single base change occurs at lt 1 it is considered to be a mutation. However, this definition is often disregarded, instead 'mutations' occurring at lt 1 in general populations might more appropriately be termed low frequency variants. The term 'mutation' is...
Data Management And Mining
Efficient application of knowledge relies on well organized data and genetics is highly dependent upon good data, often in very large volumes. Accessing available data, particularly in large volumes is often the biggest informatic frustration for geneticists. Here we focus on aspects of accessing data from public databases solutions for in-house data collection, either in the form of 'off the shelf' or custom-built laboratory information management systems LIMS belong to a specialist area that...
Secondary Accession Numbers
From Figure 4.1 we can read eight secondary accession numbers that designate protein translations for each of the BACE mRNAs. It also has three RefSeq numbers NM_012104 for the mRNA, NP.036236 for the protein and NT_009151 for the genomic contig. There is one SwissProt accession BACE_HUMAN P56817 and one TREMBL splice variant Q9BYB9. The LocusID, 23621, in turn links out to many other accession numbers which point to the BACE genome sequence. These include the Hs.49349 UniGene cluster that...
The Human Gene Mutation Database HGMD
The HGMD was established in April 1996 to collate published germline mutations responsible for human inherited disease. In October 2001, HGMD contained 26,637 mutations in 1153 genes. The scope of HGMD is limited to mutations leading to a defined inherited phenotype, including a broad range of mechanisms, such as point mutations, insertion deletions, duplications and repeat expansions within the coding regions of genes. Somatic mutations and mutations in the mitochondrial genome are not...
The Mitelman Chromosome Abberations Map
Cytogenetic studies over the past few decades have revealed clonal chromosomal aberrations in over 100,000 human neoplasms. Many of these have been characterized at the molecular level, revealing previously unknown genes that may be closely associated with tumourigenesis. Information on chromosome changes in neoplasia has grown rapidly, making it difficult to identify all recurrent chromosomal aberrations. The Mitelman Map of Chromosome Aberrations in Cancer Mitelman et al., 1997 was first...
SNP per
interferon alpha, beta and omega receptor 2 NM 000874 Genbank iorort NP 000865 SNPsel Told number of SNPfr 29 Sil 33932 Average distance 1170 R 1u ii 0 VtnMt SNFk 29 r VflWajfdSNPi r Promoter f UTR r EXVM r icquiBce Email't.- S'-'I lt ,- to yourself Figure 3.5 The SNPper gene report. The report displays SNP positions, alleles and the genomic sequence surrounding the SNP. It also presents text reports which mark up SNPs across the entire genomic sequence of the gene and amino acid-altering SNPs...
Submitting Data to dbSNP
The dbSNP database accepts direct data submissions from researchers by e-mail or FTP. The submission process is generally intended for large batch submissions involving hundreds or thousands of SNPs, using a text flatfile submission format. Each SNP submission Figure 3.3 The dbSNP freeform search interface. Figure 3.3 The dbSNP freeform search interface. contains many elements to describe the SNP, but primarily it should contain a report describing how to assay the SNP, the SNP sequence...
SNPper
SNPper is a web-based tool developed by the Children's Hospital Informatics Program CHIP , Boston Riva and Kohane, 2001 . The SNPper tool maps dbSNP RefSNPs to known genes, allowing SNP searching by name e.g. using the dbSNP 'rs' name , or by the golden path position on the chromosome. Alternatively, you can first find one or more genes you are interested in and find all the SNPs that map across the gene locus, including flanking regions, exons and introns. SNPper produces a very effective gene...
Analysing A Novel Gene
Sooner or later experimental results will locate a piece of GP where there are no fully annotated known genes. Figures 4.4, 4.5 and 4.6 show selected tracks from the Ensembl, UCSC and NCBI displays between the 3' side of the BACE gene and the 5' end of the next known gene PCSK7. The known genes are marked in brown in Ensembl and blue in UCSC. The latter are mRNA mappings and therefore include the UTR sections. Let us assume a genetic linkage study had found significant associations in this...
Candidate SNPs SNP to Assay
As we have already demonstrated, the dbSNP dataset has one overwhelming caveat most of the SNPs are 'candidate' SNPs of unknown frequency and are unconfirmed in a laboratory assay. This translates to the simple fact that many SNPs do not exist at a detectable frequency in any population. Over 60 of the SNPs in dbSNP were detected by statistical methods for identification of 'candidate' SNPs by comparison of DNA sequence traces from overlapping clones. Marth et al. 2001 investigated the...
Nucleic Acid Secondary Databases
For the analysis of their results the geneticist must become acquainted with these feature-rich sources of gene product information. A key example, based around nucleic acid sequence but including protein of secondary databases is LocusLink RefSeq LLRS for mRNAs. The LLRS system is built round a reference sequence RefSeq which is usually the longest available mRNA of those coding for the same protein. RefSeq includes splice variants and if only genomic sequence is available, such as for many of...