Whole-Exome Sequencing In A Chinese Pedigree With Hirschsprung Disease

Objective Whole-exome sequencing was preceded in2individuals from a HanChinese family with Hirschsprung Disease (HSCR), then multi-step-screening wasmade for the data from sequencing to choose the susceptible genes preliminarily ofHSCR.Method We chose a mother and a son from a family, both of them had beenidentified as HSCR patient. The peripheral blood was obtained from the two and thencaptured the whole-exome sequences using SOLID4DNA Kit according to themanufacturer’s protocols. The results were filtered against the human databases ofHAPMAP8, dbSNP130and1000Genome Project, and common variations which hadbeen reported were wiped out, then non-synonymous single nucleotide variants(SNVs) from the mother and the son were combined, and candidate genes wasselected initially.Result Comparing the sequencing data with the human databases of HAPMAP8,dbSNP130and1000Genome Project, we found13948SNVs of the mother and13856SNVs of the son in the exome zone after screening. Among these SNVs,3472of the mother and3345of the son was unreported before, and the amount ofnon-synonymous SNVs was470of the mother and458of the son. After combiningthe mutual non-synonymous variations from the two,16genes were screened out.Conclusions The16genes (NRG3；LAMA3；BRIP1；JARID2； KRT6A；LEPREL1；OR8J3；PLA2G4C；PRBP4；RNF10；SPRY1；TMPRSS11E；VARS2；NBPF16；GSTM4；PRSS1) might be the susceptible genes of HSCR, but much moreinvestigations must be carried out to prove this.