Description

This track shows alignments of the human genome with itself, using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. The system can also tolerate gaps in both sets of sequence simultaneously. After filtering out the "trivial" alignments produced when identical locations of the genome map to one another (e.g. chrN mapping to chrN), the remaining alignments point out areas of duplication within the human genome. The pseudoautosomal regions of chrX and chrY are an exception: in this assembly, these regions have been copied from chrX into chrY, resulting in a large amount of self chains aligning in these positions on both chromosomes.

The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the query assembly or an insertion in the target assembly. Double lines represent more complex gaps that involve substantial sequence in both the query and target assemblies. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one of the assemblies. In cases where multiple chains align over a particular region of the human genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes.

Chains have both a score and a normalized score. The score is derived by comparing sequence similarity, while penalizing both mismatches and gaps in a per base fashion. This leads to longer chains having greater scores, even if a smaller chain provides a better match. The normalized score divides the score by the length of the alignment, providing a more comparable score value not dependent on the match length.

Display Conventions and Configuration

By default, the chains are colored by the normalized score. This can be changed to color based on which chromosome they map to in the aligning organism. There is also an option to color all the chains black.

To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome.

By default, chains with a score of 20,000 or more are displayed. This default value provides a conservative cutoff, filtering out many false-positive alignments with low sequence similarity, or high penalties. It should be noted however, that alignments below this threshold may still be indicative of homology.

In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment.

Methods

The genome was aligned to itself using blastz. Trivial alignments were filtered out, and the remaining alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single target chromosome and a single query chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. Chains scoring below a threshold were discarded; the remaining chains are displayed in this track.

Credits

Blastz was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison.

Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program.

The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler.

The browser display and database storage of the chains were generated by Robert Baertsch and Jim Kent.

References

Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput 2002, 115-26 (2002).

Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9.

Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7.