The DNA sequence and analysis of human chromosome 13

Abstract

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Figure 1

Genetic and physical characteristics of the chromosome 13 sequence. a, A comparison of physical and genetic distance along chromosome 13. Markers from the deCODE genetic map were localized in the sequence. Their locations in the genetic map are plotted on the y axis and locations in the sequence are on the x axis (the sequence starts at position 17,918,001 to allow for the chromosome short arm and centromere). The female genetic map is shown in orange, the male map in green and the sex average map in red. The loci shown mark the extent of the region of low gene density (D13S1269–D13S71), the recombination jungle (D13S1315–D13S1825) and the recombination desert (D13S1301–D13S233). b, Variation in features along the chromosome. The sequence was divided into 1-Mb non-overlapping sections, and each section was studied for the features shown. The data for each feature were normalized to set the largest figure at 100% and the lowest at 0%. For the repeat coverage, the interspecies sequence homologies (defined in the Methods), and the exon and gene coverage, the percentage of each 1-Mb window is calculated. The range of data points for each plot are as follows: % G+C content (33.5–52.4); % SINE coverage (3.5–25); % LINE coverage (9.2–31.4); % with homology to mouse (1.1–14.2); % with homology to rat (0.9–11.9); % with homology to Tetraodon (0–1.8); % with homology to zebrafish (0–3); % with homology to Fugu (0–1.9); % exon coverage (0–4.1); genes per Mb (0–38); % gene coverage (0–100); ncRNAs per Mb (0–6); pseudogenes per Mb (0–24).

Figure 2

Characteristics of a gene-rich (a) and a gene-poor (b) region. The overlapping tilepath, labelled by accession number, is shown in yellow. Genetic markers from the deCODE map have been positioned on the sequence. Occurrences of repeats are shown as vertical turquoise bars. G+C content and CpG dinucleotide content are shown in overlapping windows of 8 kb, with adjacent windows overlapping by 4 kb. CpG islands are predicted using a modification of the CpG program developed by G. Micklem (personal communication). The positions of transcription start sites were predicted by the Eponine program. Regions conserved in mouse and rat are shown by orange bars, and those conserved in Fugu​, Tetraodon and zebrafish are shown by green bars. The Rfam track contains the predicted ncRNA genes. Annotated gene structures are shown, subdivided into categories by colour. The direction of transcription is indicated by the arrow. The SNP tracks indicate the number of SNPs per kb. The random SNPs were generated by the whole-genome shotgun approach and were obtained from dbSNP by querying for SNPs produced by The SNP Consortium. The locations of clusters of two or more related genes within 1 Mb of each other are indicated. The scale shows the approximate Mb position along the chromosome. The chromosome view is available in Supplementary Fig. S1.

Figure 2

Characteristics of a gene-rich (a) and a gene-poor (b) region. The overlapping tilepath, labelled by accession number, is shown in yellow. Genetic markers from the deCODE map have been positioned on the sequence. Occurrences of repeats are shown as vertical turquoise bars. G+C content and CpG dinucleotide content are shown in overlapping windows of 8 kb, with adjacent windows overlapping by 4 kb. CpG islands are predicted using a modification of the CpG program developed by G. Micklem (personal communication). The positions of transcription start sites were predicted by the Eponine program. Regions conserved in mouse and rat are shown by orange bars, and those conserved in Fugu​, Tetraodon and zebrafish are shown by green bars. The Rfam track contains the predicted ncRNA genes. Annotated gene structures are shown, subdivided into categories by colour. The direction of transcription is indicated by the arrow. The SNP tracks indicate the number of SNPs per kb. The random SNPs were generated by the whole-genome shotgun approach and were obtained from dbSNP by querying for SNPs produced by The SNP Consortium. The locations of clusters of two or more related genes within 1 Mb of each other are indicated. The scale shows the approximate Mb position along the chromosome. The chromosome view is available in Supplementary Fig. S1.

Figure 3

MultiPipMaker analysis of the human DACH1 gene showing conserved regions in mouse, rat, Fugu and zebrafish. a, The complete gene, with strongly aligned regions (at least 100 bp without a gap and with at least 70% nucleotide identity) in red. The green lines indicate regions conserved by local alignments. Exons are numbered. b, A more detailed picture of the area around exon 6. The arrow indicates a conserved intronic sequence which has 100% homology to a putative miRNA predicted using MiRscan