Friday, May 11, 2012

Updating the genome: correcting the assembly of 10q11.22

Human GRCh37 patch release 8 contains an update to previously released fix patch HG1211_PATCH.

This encompasses a 3Mb region in GRCh37 between chr10: 46,256,855-49,299,273.

The tile path in the 10q11.22 region has been extensively altered from its previously fragmented state to one where a single gap remains, between BX649215.1 and AC245041.3. The reworking of the tile path in the region has been carried out using clones in the existing build and additional finished clones not previously in GRCh37.

Working with optical map data provided by the Schwartz Lab we have been able to identify errors in the GRCh37 assembly and have consequentially worked to correct them. The optical map analysis also highlighted redundancy in the assembly causing artificial duplication, which has now been addressed within this patch.
Above: Optical map consensus alignments to GRCh37 10q11.22.
Below: Optical map consensus alignments to the fix patch (JH591181.2)
Legend: Pink track: Clone path; Green: Contig gap; Blue: In silico SwaI fragments.
For the aligned optical map consensus Gold: Concordant fragment ; Red: Missing fragment (seen where OM consensus span gap); Grey: Unaligned fragment

The optical map information was consistent with a path problem in this region. The map data suggested that several clones in the region were misplaced and did not represent a valid chromosome structure in this region. In addition to rearranging several clones (including changing the orientation of some clones in the path), 3 finished clones were added to the path and several redundant clones were removed. The new path contains a single gap that we estimate, based on optical mapping, to be about 90 Kb. The figure below shows an alignment of the patch sequence to the current chr10 assembly.
The panel to the left shows an overview of chr. 10. The orange dots represent fix patches we've released and the blue dots represent novel patches. The arrow shows the location of the 10q21 fix patch. To the right, the top panel shows the chr. 10 tiling path (in grey), the annotated RefSeq genes are below that (in green) and the alignment to the fix patch below that (in purple). The bottom panel shows the patch tiling path and alignment to the chromosome. 

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