Figure 8.

Linkage and haplotype structure at the chr7q35 trypsinogen locus

(A)LD matrix calculated from 10XG phased calls; deletion allele is denoted by orange rectangle. Haplotype blocks are drawn as black triangles, and all five trypsinogen paralogs are located within a single block (KI270803.1:737033–802909). Meconium ileus GWAS summary statistics lifted from GRCh37 to KI270803.1 are shown, R² with respect to rs3757377.

(B)Four SNPs in the same LD block as rs3757377, phased with the deletion polymorphism. SNPs include a common pancreatitis risk allele (rs10273639),¹⁸ a PRSS1 promoter SNP (rs4726576) that alters expression of a reporter gene in mice,¹⁹ and two synonymous PRSS1 variants (rs6666 and rs6667). Five unique haplotypes are observed in 10XG data, and the frequencies are shown as a percentage. The two major haplotypes account for 94.7% of the observed data. The two rarest haplotypes (1% of the observed data) were supported by manual inspection in IGV.