The Bioinformatics Study On TYR Gene Mutations And Its' Pathogenic Mechanism In OCA1 Patients

In this study,we will analyze the molecular basis and mutations' nosogenesis on oculocutaneous albinism type 1.Oculocutaneous albinism(OCA) is a group of autosomal recessive disorders characterized by reduced or absent biosynthesis of melanin in melanocytes of the skin, hair follicle and eyes.It is the most common form of albinism and can be separated into four types:OCA1,OCA2,OCA3 and OCA4.OCA1,which results from mutations of the tyrosinase,is one of the most serious and common types of OCA.In order to explore the mutation spectrum of TYR gene in China,we analyzed the TYR gene of 6 COA1 patients by use of direct sequencing.We had detected 6 kinds of mutations,including 2 missense mutations(R299H,W400L),and 2 nossense mutations(R116X,G295X),2 insertion mutation(232insGGG,929insC).G295X is a novel mutation which hasn't reported yet before.It seemed that them are two most common mutations,W400L accounted for about 25%(3/12) in Chinese OCA1 alleles, while R116X accounted for about 33.3%(4/12).The experimental results showed that the TYR gene mutation spectrum is different between Chinese population and other countries'.With breakthroughs in bioinformatics development,it had a significant impact on genomics,proteomics,and information science,computer and network technology, new drug development and other fields,and promoted the progress of the trial.This study focused on the forefront,use of various database BLASTP,ClustalW, Scanprosite,Translates,SAPS,such as practical,high-performance bioinformatics software forecasted and analysised the OCA1 related four pathological mutations W400L,929insC,R299H,232insGGG,in protein structure and function.,and trying to identify these pathological molecular mechanism in DNA and protein level,for some new mutations of the TYR protein provided the useful reference value about judge to pathogenic mutation.The results of four pathogenic mutations bioinformatics analysis showed that the pathogenic mutations and changes in protein structure and function related to the TYR protein superfamily,species homology,protein secondary structure,protein function and protein structure space,that is indications that TYR mutation resulted in protein structure and function had changed.Our research accumulates data for gene diagnosis and prenatal gene diagnosis which is aim directly at negative eugenics of OCA1,having profound practice meaning in the aspect of albinism genetic counseling,precention and aristogenesis in our country.Accumulates experience on the use of Bioinformatics make some reasonable interpretation about TYR gene mutation in the feture study,and provided some important valuable information with pathogenic mutations judge on patients.