Whole-Exome Sequencing In A Pedigree With Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Objective:Whole-exome sequencing was preceded in3individuals from a family with HNPCC in order to choose the susceptible genes of HNPCC.Method:We chose three patients from a family,all of them had been identified as HNPCC patient.The peripheral blood was obtained from all of them. High-throughput sequencing was carried out by the technology of the exon trapping.The results were filtered against the human databases of HAPMAP8,dbSNP130and1000Genome Project,and common variations which had been reported were wiped out,then non-synonymous single nucleotide variants(SNVs) from three patients who are brothers and sisters were combined,and candidate genes was selected initially.Results:â‘ A total of60.4G data was obtained from three patients in a typical HNPCC family by using the technology of the exon trapping.â‘¡Comparing the sequencing data with the human databases of HAPMAP,dbSNP130and1000Genome Project, we found91224395SNVs of the proband and133,688,255SNVs of the brother and105,656,069SNVs of the sister in the exome zone after screening. Among these SNVs,83257847of the proband and120411348of the brother and95653932of the sister was unreported before, After combining the mutual non-synonymous variations from the three,3genes (SFT2D3, AMH, HTRA1)were screened out.Conclusions:.â‘ It seems that candidate gene mutations of HNPCC can be found by Exon sequencing.â‘¡SFT2D3, AMH, HTRA1might be the susceptible genes of HNPCC,but much more investigations must be carried out to prove this.Table9,chart10,reference66.