Development of association analysis method for rare diseases based on comprehensive HLA typing with multiple risk factors

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18474
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Kyoto University
• Principal Investigator: Kawaguchi Shuji 京都大学, 医学研究科, 助教 (00525404)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: HLA / 次世代シークエンサー / タイピング / アルゴリズム / 遺伝統計学 / マルチプレックスPCR

Outline of Final Research Achievements

We have established novel sequencing and typing technologies for HLA genes that can type more comprehensive HLA alleles with high resolution than conventional typing method. We have also developed a method for association analysis that can derive susceptible or protective amino acid residues on HLA protein with considering various risk factors of disease development. By using the developed methods, we carried out HLA typing of 928 patients of HTLV-1 associated myelopathy (HAM), 2,398 asymptomatic HTLV-1 carriers and 2,553 uninfected controls, and conducted association study between HLA genes and HAM development. As a result, we could identify susceptible and protective amino acid residues for HAM development that have different effect with proviral load.

Free Research Field

統計科学

Academic Significance and Societal Importance of the Research Achievements

従来のHLAアレルのタイピング方法は、高コストでありながら得られる精度や情報が少ないため、解析を行うためのサンプル数の不足や、得られたHLAアレルやアミノ酸残基の頻度に歪みが生じるといった問題が存在した。本研究で確立したHLA解析技術を用いることで、高精度でありながら低コストにHLA遺伝子解析を行うことが可能であり、様々な難治性疾患における発症リスクや診断に有用となるバイオマーカーの発見が期待できる。