The New Method Of HLA Gene Family Type Inference And The Identification Of Psoriasis-related Types

MHC is a major histocompatibility complex,and its encoded molecules are involved in antigen presentation,restricting mutual recognition between cells,and inducing immune responses.Human MHC is commonly referred as the HLA gene.Psoriasis is an immune mediated hereditary skin disease,the disease cycle is long,easy to relapse.Some patients may be not cured throughout the life.Some patients may not recover from life.The main cause of the disease is young adults,and the impact on the patient’s physical health and mental state after the illness is relatively large.Because HLA,type is heritable,the relevant HLA,type controlling psoriasis can be judged by studying HLA.Sanger sequencing is currently the most accurate and high-resolution method for HLA typing,but the sequencing cost is too high and the throughput is very low.In contrast,regionbased second-generation sequencing can realize high-throughput typing,which can be achieved by combining appropriate bioinformatics analysis and statistical algorithms.It is an ideal technique,but this technology requires sofisticated statistical methods,and the computational speed is demanding depends on the method used.In this experiment,a new HLA typing algorithm based on second-generation sequencing technology was developed.The sequencing read depth and an iterative algorithm were used to accurately classify the haplotypes on two homologous chromosomes.The results of the Sanger sequencing HLA typing of 100 individual was selected from the 1,000 Genome project as the "gold standard" to judge the accuracy of the new method and compared to the polysolver software.The results showed that the new algorithm can accurately classify the HLA genes,the correct rate is up to 97%,which is 0.3% higher than that of the polysolver.Moreover,the calculation speed is about 1 times higher than the polysolver,and the new algorithm takes about 80 minutes.The polysolver takes about 150 minutes.This experiment also applied the new method to detect HLA types underling psoriasis.The sequences of 500 individuals were selected as the study subjects,including 250 psoriasis patients and 250 healthy people.The Fisher’s exact test was used to detect causal HLA types.As results,we found three HLA types,HLA-A*24*01,HLA-B*08*01 and HLA-C*06*02,of which HLAC*06*02 has been proven by many research groups to be associated with psoriasis,and the other two genes require further studies to determine whether they are associated with psoriasis.By constructing an accurate identification method for HLA genotypes and applying the new method to the identification of psoriasis-related types,it provides reference for similar research on other diseases,diagnosis,treatment and related organisms of HLA-related diseases.