ABSTRACT
We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.
Subject(s)
Chromosome Mapping , Genetic Loci , Genome , Haplotypes , Mice, Inbred Strains/genetics , Animals , Animals, Laboratory , Chromosome Mapping/veterinary , Haplotypes/genetics , Mice , Mice, Inbred BALB C/genetics , Mice, Inbred C3H/genetics , Mice, Inbred C57BL/genetics , Mice, Inbred CBA/genetics , Mice, Inbred DBA/genetics , Mice, Inbred NOD/genetics , Mice, Inbred Strains/classification , Molecular Sequence Annotation , Phylogeny , Polymorphism, Single Nucleotide , Species SpecificityABSTRACT
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
Subject(s)
Algorithms , Contig Mapping/methods , Genome/genetics , Sequence Analysis, DNA/methods , Databases, Genetic , Escherichia coli/geneticsABSTRACT
MOTIVATION: The rapidly increasing set of sequenced genomes highlights the importance of identifying the synteny blocks in multiple and/or highly duplicated genomes. Most synteny block reconstruction algorithms use genes shared over all genomes to construct the synteny blocks for multiple genomes. However, the number of genes shared among all genomes quickly decreases with the increase in the number of genomes. RESULTS: We propose the Duplications and Rearrangements In Multiple Mammals (DRIMM)-Synteny algorithm to address this bottleneck and apply it to analyzing genomic architectures of yeast, plant and mammalian genomes. We further combine synteny block generation with rearrangement analysis to reconstruct the ancestral preduplicated yeast genome. CONTACT: kspham@cs.ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.