Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations

Tryptase deficiency alleles (α and the newly discovered βIIIFS) are common, causing the number of inherited active genes to range from a minimum of 2 to a maximum of 4, with major differences between populations in the proportion of individuals inheriting 2 versus 4 active alleles. African and Asian populations are especially enriched in genes encoding functional and nonfunctional tryptases, respectively. Strong linkage of TPSAB1 and TPSB2 and pairing of deficiency alleles with functional alleles in observed haplotypes protect human subjects from “knockout” genomes and indeed from inheritance of fewer than 2 active alleles.