The genome of the chicken DT40 bursal lymphoma cell line.
Bottom Line: In a comparison to two domestic chicken genomes and the Gallus gallus reference genome, we found no unique mutational processes shaping the DT40 genome except for a mild increase in insertion and deletion events, particularly deletions at tandem repeats.We mapped coding sequence mutations that are unique to the DT40 genome; mutations inactivating the PIK3R1 and ATRX genes likely contributed to the oncogenic transformation.The sequence data generated by this study, including a searchable de novo genome assembly and annotated lists of mutated genes, will support future research using this cell line.
Affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.Show MeSH
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Mentions: The SNP array shows multiple genomic regions that lack heterozygous SNPs, most notably a large part of chromosome 2 (Figure 2B). The genome sequence allows a more detailed view of regions of copy number neutral LOH (referred to simply as LOH). We calculated the ratio of heterozygous to homozygous SNVs in 100-kb sequence blocks along each chromosome and detected an average of 322 homozygous and 306 heterozygous SNVs per 100 kb; 26% of the sequence blocks have a heterozygous-to-homozygous (het/hom) ratio less than 0.1, which we classified as LOH. A further 8% contained fewer than 50 homozygous SNVs and were not used for LOH classification. In the L2 and Silkie breed samples, we classified 33% and 30% of the genome as LOH regions, respectively, indicating that there is no overall DT40-specific process resulting in large-scale LOH. The size distribution of the LOH regions is also similar between DT40 and the two domestic breeds (Figure 3A), although there is a greater incidence of short LOH regions (100–200 kb), possibly indicating higher homologous recombination activity in DT40. The size distribution suggests the presence of a larger number of LOH regions below the 100 kb size, but the SNV density does not allow a reliable detection of smaller regions. The position of the LOH regions is mostly unique in the three investigated samples, as illustrated on a selected chromosome (Figure 3B). The two largest LOH regions in the DT40 genome on chromosomes 2 and 20 were confirmed by the Sequenza analysis (Figure 2B). A table of the LOH regions in the DT40 genome at 100-kb resolution is presented as supplementary information (Table S2).
Affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.