Exploring The Genetic Susceptibility To Penicillium Marneffei Infection By Whole Exome Sequencing

Objective:Exploring the genetic susceptibility to Penicilliosis marneffei(PSM) by whole exome sequencing technique would provide key information for susceptible genes and conclude the mechanism of PSM susceptibility.Explore relationship between anti-interferon-gamma autoantibody and PSM patients without HIV infection.Methods:The PSM patients,including 3 young patients and their healthy parents,60 without HIV infectious,and 62 healthy volunteers have been included in this project from 2013-2016.(1)Genomic DNA from this 3 patients and their parents was extracted and purified,then for whole exome sequencing.Compared with human genomic DNA database,mutation information of SNP and Inde was obtained.Filtering mutation information in and between families by bioinformatics analysis could find out the candidate genes.(2)Dectecting serum anti-interferon antibody from PSM patient without HIV infection and healthy volunteers and explore the possible reason of PSM susceptible infection.Results:(1) The mean sequencing depth on whole exome sequencing target regions was 111.66-fold.Data quality control was more than 90% to make sure the error rate of sequencing was less than 1%.During the sequencing,mutation information of 72682 SNPs and 6505 Indels was obtained. We conclude DOCKS mutation would be the possible reason for young patients susceptible to PSM by bioinformatics analysis and comparing to database online.(2)There was statistical significance in results of human anti-interferon antibody between PSM patients without HIV infection and healthy volunteers.Conclusion:Whole exome sequencing technique coule be explore the possible susceptible gene in PSM patients.DOCK8 mutation would play an important role in PSM susceptibility in young patients.For the adult patients, adult-onset immunodeficiency due to anti-interferon-gamma antibody could be related to PSM.