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Extended Data Fig. 1 | A panel of 2,530 reference haplotypes (created from
WGS data) containing C4 alleles and SNPs across the MHC genomic region
enables imputation of C4 alleles into SNP data. a, Distributions (across 1,265
individuals) of total C4 gene copy number (C4A + C4B), as measured from read
depth of coverage across the C4 locus, in WGS data. b, The relative numbers of
reads that overlap sequences specific to C4A or C4B (together with the total C4
gene copy number as in a) are used to infer the underlying copy numbers of the
C4A and C4B genes. For example, in an individual with four C4 genes, the
presence of equal numbers of reads specific to C4A or C4B suggests the
presence of two copies each of C4A and C4B. Precise statistical approaches
(including inference of probabilistic dosages) and further approaches for
phasing C4 allelic states with nearby SNPs to create reference haplotypes, are
described in Methods. c, The SNP haplotypes f lanking each C4 allele are shown
as rows (SNPs as columns), with white and black representing the major and
minor allele of each SNP. Grey lines at the bottom indicate the physical location
of each SNP along chromosome 6. The differences among the haplotypes are
most pronounced closest to C4 (towards the centre of the plot), as historical
recombination events in the f lanking megabases will have caused the
haplotypes to be less consistently distinct at greater genomic distances from
C4. The patterns indicate that many combinations of C4A and C4B gene copy
numbers have arisen recurrently on more than one SNP haplotype, a
relationship that can be used in association analyses (Fig. 1b).