TPSAB1 copy number




Principal Investigator:

Anna Lindstrand


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30107: Medical Genetics



The tryptase locus harbour four tryptase encoding genes (TPSG1, TPSB2, TPSAB1, and TPSD1); together, these genes encode Tryptase alpha-1 and Tryptase beta-1, two proteases expressed in mast cells and basophils, respectively. Notably, the TPSAB1 copy number is variable, and 5% of the Swedish population is estimated to carry multiple copies of TPSAB1. The expression of TPSAB1 correlates with the TPSAB1 copy number, and individuals carrying additional copies of TPSAB1 (> 1 per allele) may be affected by hereditary alpha tryptasemia; an autosomal dominant trait responsible for a wide range of disorders, ranging from unaffected individuals, allergies, sleep disorders, and more severe phenotypes, such as congenital skeletal abnormalities. In this study, we will utilize WGS data to estimate the TPSAB1 copy number in 300 patients affected by various connective tissue disorders. These patients have previously been sequenced through Clinical genomics, Solna. The copy number estimation will be performed using AMYCNE, an in house developed tool designed for accurate WGS based copy number estimation. The results will be compared to ddPCR, as well as to AMYCNE TPSAB1 copy number profiles in 1000 healthy Swedish individuals (i.e. the SweGen dataset). The aim of these analyses is to setup ddPCR as a diagnostic test at clinical genetics Solna, to create a high resolution map of the TPSAB1 copy number in the Swedish population, and to gain novel insights on the pathogenicity of hereditary alpha tryptasemia.