Analysis Of Low Frequency Variation With Hereditary Deafness-related Genes In Yunnan Four Ethnic Deaf Population

objectivesDeafness,also known as hearing impairment,,mainly manifested in varying degrees of hearing loss,leading to language communication disorders that seriously affect the quality of life of affected populations.According to the World Health Organization?WHO?,there are approximately 360 million people worldwide who have hearing problems.There are many factors that cause deafness,which can be basically divided into genetic factors and non-genetic factors.Deafness caused by genetic factors such as genetic and chromosomal abnormalities is called hereditary hearing loss?HHL?.For HHL genes have a large number of exons,the traditional sequencing method has low detection of such genes,and there is a deficiency in the identification of pathogenic mutations.With the emergence of next-generation sequencing technology,sequencing of large quantitative data become possible.In the HHL genes there exists many lowfrequency mutations which do not have enough data in the database or lack of functional verification.This brings many difficulties to the subsequent analysis of the second generation sequencing.There are many ethnic minorities in Yunnan,and the genetic background of deaf people is also complicated.We selected samples from four different ethnic deaf patients in Yunnan with target region capture and high-throughput sequencing,and then used bioinformatics techniques to analyze the results,in order to provide a certain reference data for the prevention and control of HHL in Yunnan.MethodsTarget region capture and high-throughput sequencing of peripheral blood genomic DNA from Han,Yi,Dai and Hani patients in Yunnan,using all exons of 124 hereditary deafness-related genes and 100 bp per extension on both sides of each exon as target regions,bioinformatics analysis was used to find the mutations and statistically analyzing the occurrence sites to draw the mutation spectrum about the HHL genes of Han,Yi,Dai and Hani deaf patients in Yunnan.ResultWe collected the sample of 179 patients with GJB2 negative,including 34 Hani,27 Dai,75 Yi,and 43 Han.Among the 124 HHL genes in deaf patients in Yunnan,there are 110 genes have low frequency mutation sites.The genes that appear in the Han deaf population are: LRP2?7%?,ADGRV1?5%?,COL11A1?5%?,and DIAPH3?4%?etc.The low frequency variation are: rs759076090?LRP2?,rs60522638?ADGRV1?,103471454?COL11A1?,NM₀01042517: exon25: c.3028-2->TAAG?DIAPH3?etc.The genes that appear in the Yi deaf population are: LRP2?8%?,ADGRV1?6%?,MYO7A?4%?,and DIAPH3?4%?etc.The low frequency variation are: rs759076090?LRP2?,rs60522638?ADGRV1?,rs111906251?MYO7A?,NM₀01042517: exon25: c.3028-1-> ATA?DIAPH3?etc.The genes that appear in the Dai people's deaf population are: LRP2?9%?,ADGRV1?5%?,COL11A1?5%?,and PTPRQ?4%?etc.The low frequency variation are: rs759076090?LRP2?,rs60522638?ADGRV1?,rs749687230?COL11A1?,rs111906251?PTPRQ?and so on.The genes appear in the Hani deaf population: LRP2?9%?,USH2A?6%?,ADGRV1?5%?,and OTOF?4%?etc.The low frequency variation are: rs759076090?LRP2?,rs140003076?USH2A?,rs60522638?ADGRV1?,rs752266635?OTOF?etc.ConclusionWe compared the hereditary deafness-related pathogenic genes with low frequency mutations in the top 30 of the four different ethnic groups in Yunnan,and found that: 1)The low frequency mutation sites in the deaf population of the Yi and Dai are: rs759076090?LRP2?,rs60522638?ADGRV1?,rs140003076?USH2A?,etc.,of which rs759076090 is similar in the two populations,while rs60522638 and rs140003076 has a difference.2)The low frequency mutation sites in the Yi and Hani deaf populations are: rs759076090?LRP2?,rs60522638?ADGRV1?,rs367660058?TRIOBP?,etc.,of which rs60522638 accounts for a large difference in the two nations.3)The low frequency mutation sites in the deaf population of the Yi and Han are: rs759076090?LRP2?,rs60522638?ADGRV1?,NM₀01042517: exon25: c.3028-1->ATA?DIAPH3?,etc,among which NM₀01042517 : exon25:c.3028-1->The ATA is similar in the two nations,and the other sites account for a large difference.4)The low frequency mutation sites in the Dai and Hani deaf population are: rs759076090?LRP2?,rs140003076?USH2A?,rs145588841?TRIOBP?etc.Among them,the proportion of rs140003076 in the two nations is quite different.5)The low frequency mutation sites existing in the deaf population of the Yi and Han are: rs759076090?LRP2?,rs60522638?ADGRV1?,103471454?COL11A1?and so on.Among them,103471454 has a large difference in the proportion of the two nations.6)The low frequency mutation sites in the Hani and Han deaf populations are: rs759076090?LRP2?,rs60522638?ADGRV1?,rs762586713?TRIOBP?etc.Among them,rs762586713 is similar in the two nations,and the other sites have large differences.In summary,there are many different low-frequency variant sites of HHL genes in the deaf population in Yunnan,and their distribution among these 4 ethnic groups is different.