*** Overview ***

The VCF files contain small indel calls for the CEU and YRI trios. 
The calls were made from MAQ-aligned Broad-recalibrated Illumina BAM files,
using the indel caller Dindel (Albers et al). 454 and SOLID data were not 
considered in the analysis, not for the actual calling and also not for
the detection of candidate indels.


*** Procedure ***

The calls were made as follows:
1. Extract all indels in MAQ alignments from the BAM file. These are 
   the candidate indels.
2. Generate genotype likelihoods using Dindel for every candidate indel
3. Assuming Mendelian inheritance, calculate the posterior probability for 
   each indel genotype in all three trio members jointly.

Thus, the VCF files only contain indels that are consistent with Mendelian
inheritance. Independent analysis of the trio members indicated that there 
is signficant number of cases where the trio-child shows evidence for an indel,
but none of the parents does; these cases are not included in the VCF file.
Such cases are likely explained by reduced sensitivity for detecting indels 
as compared to SNPs, mapping errors, and some may be a result of de novo 
mutations. We hope to address these issues in future releases 
by using more sensitive mapping and indel calling algorithms.

NOTE    As described above, all reported calls are consistent with Mendelian 
	inheritance by construction. These VCFs are therefore not useful 
	for mutation analysis.

NOTE 	The second sample in the genotype file is that father, the third is 
	sample is the mother.

*** LOF variants ***

In coding regions, indel rates are significantly lower due to selection,
and since noise levels (factors resulting in false positives) are expected to be 
approximately constant across the genome, the false discovery rate of the indel
call set will be increased in coding regions. To lower the number of false positive 
indel calls, we applied more stringent filters to the
subset of indels that were called in the genome-wide set and were predicted to
fall into the LOF class. The stringent filter requires that the range of
positions where an indel would yield the same alternative haplotype sequence as
the original called indel (for instance, in a repeat, the deletion of any repeat
unit would give the same alternative haplotype), plus 4 bases of reference
sequence on both sides of this region, was covered by at least one read on the
forward strand, and at least one read on the reverse strand, with at most one
mismatch between the read and the alternative haplotype sequence resulting from
the indel (regardless of base-qualities). This filter removed the excess of 1-bp
frameshift insertions seen in CHBJPT with respect to CEU in the less stringently
filtered genome-wide indel call set, although it is expected to remove a
significant number of true positive calls as well. The indels that pass this
stringent filter have been annotated in the VCF files by 'SF' in the INFO
field.


If you have any questions, please contact me (Kees) at caa (at) sanger.ac.uk

Kees Albers 
Gerton Lunter
Richard Durbin