Ensembl variation resources

Abstract

Background: The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics.

Description: The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl.

Conclusions: Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at http://www.ensembl.org and from the public MySQL database server at ensembldb.ensembl.org.

Figure 1

Variation summary for rs2476601. Label 1 indicates the links to information for this specific variant. Label 2 indicates the summary, which includes the source (dbSNP), synonyms or other IDs for this variant in other databases or array platforms, alleles found and genomic location. Flanking sequence is also found in the summary information but not shown in the figure. http://Mar2010.archive.ensembl.org/Homo_sapiens/Variation/Summary?source=dbSNP;v=rs2476601.

Figure 2

LD (linkage disequilibrium) plot for the region around rs2476601. LD values in this figure were calculated based on allele frequencies in the CEPH human population. The LD data between variants is represented using a triangular grid shaded on a gradient from white to red depending on the strength of the LD (where red is high LD, white is low). Hovering the mouse cursor over one of the coloured regions in the plot reveals a pop-up box displaying the two variation IDs for that coloured region, and the LD value between them. http://Mar2010.archive.ensembl.org/Homo_sapiens/Location/LD?focus=variation;pop1=CSHL-HAPMAP:HapMap-CEU;r=1:114367568-114387567;v=rs2476601;vf=1916990.

Figure 3

Variation views. Views available in the variation tab are titled with the name of the link leading to each set of information. The data in the figure correspond to rs2476601. The gene/transcript panel shows an Ensembl gene with this variant where it has different effects depending on the splice variant. Allele frequencies have been measured in four HapMap populations, as shown in the population genetics panel. The NHGRI associates Crohn's disease, Rheumatoid Arthritis and Type I Diabetes to this SNP, displayed in phenotype data. The phylogenetic context panel shows a common allele at this position in the reference sequences for chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), macaque (Macaca mulatta), mouse (Mus musculus), rat (Rattus norvegicus), horse (Equus caballus), dog (Canis familiaris), cow (Bos taurus), opossum (Monodelphis domestica), and chicken (Gallus gallus). Platypus (Ornithorhynchus anatinus) shows a different nucleotide (T).

Figure 4

Variation image. A. The variation image in the gene tab shows all transcripts for an Ensembl gene in red, and variations mapping to each transcript as coloured boxes. Intronic variants are, by default, only drawn if within 100 bp of an exon. Change this by clicking on configure this page and selecting full introns. Protein domains and motifs encoded by the transcript sequence from databases such as PIR-Superfamily, PROSITE and Pfam are drawn in purple along each transcript. B. An expanded view of the box drawn in A is shown. Label 1 indicates the exon structure of Ensembl transcript ENST00000359785. Filled boxes are coding sequence within the exons, and unfilled boxes indicate untranslated regions (UTRs). Variations are indicated by label 2, and are colour-coded as to their effect on the transcript (see legend on the page). For this transcript, many intronic (dark blue) variations are shown, along with four non-synonymous (yellow) SNPs that display the potential amino acids at each position. Label 3 indicates a PIR-Superfamily domain (purple) that maps to the protein sequence. http://Mar2010.archive.ensembl.org/Homo_sapiens/Gene/Variation_Gene?db=core;g=ENSG00000134242;r=1:114356437-114414375;t=ENST00000359785.

Figure 5

Population comparison image. The ENST00000359785 transcript is shown, along with a representation of the genomes of Craig Venter and James Watson and the reference sequence (GRCh37) in this region. The left hand side of the view shows links available from the transcript tab. Label 1: The genomes of Craig Venter and James Watson have high coverage in this region (i.e. at least two sequencing reads or present for both strands of the chromosome), shown by a thick grey bar. Label 2: Variants are drawn as boxes if the allele differs from the reference sequence. A non-synonymous variation is shown in yellow, with two potential amino acids indicated (tryptophan and arginine). Label 3: The nucleotides possible for this variation are displayed upon clicking the corresponding yellow box. Label 4: A table compares each allele at positions of variation. This view indicates the alleles in both Venter and Watson's genomes are different to the reference sequence allele, for this variation. Watson is heterozygous at this position, and Venter is homozygous. http://Mar2010.archive.ensembl.org/Homo_sapiens/Transcript/Population/Image?db=core;g=ENSG00000134242;r=1:114356437-114414375;t=ENST00000359785.

Figure 6

The cDNA sequence for ENST00000359785. A. The untranslated region (UTR) is highlighted in yellow. Numbering of the first line begins at 1 at the start of the UTR. Numbering of the second line starts at 1 at the beginning of the coding sequence. The third line shows line numbering and sequence of the protein. Codons are indicated by light yellow alternating with no highlight. B. Further down the sequence shown in A, a variation is highlighted. This variation is at position 183 in the protein sequence, 547 in the coding sequence, and 677 in the transcript sequence is shown to be rs34590413. The ID is revealed upon clicking on the IUPAC or ambiguity code above the highlighted nucleotide, which provides a link to the variation tab. The non-synonymous variations are shown by a red-coloured amino acid. Hovering over the indicated amino acid with the mouse shows the possible amino acids at that position. http://Mar2010.archive.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000134242;r=1:114356437-114414375;t=ENST00000359785.

Figure 7

Sequence alignments between the human reference sequence, GRCh37, and the genomes of Venter and Watson. Variation data are highlighted in green and indicated by an IUPAC code. A. The default display replaces nucleotides with dots if the genome has the same allele as the reference assembly. B. The display can be changed by using the matching basepairs: show all option in the configure this page link. http://Mar2010.archive.ensembl.org/Homo_sapiens/Location/SequenceAlignment?db=core;g=ENSG00000134242;r=1:114382907-114387906;t=ENST00000359785.