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Identification of rare variants of allergic rhinitis based on whole genome sequencing and gene expression profiling: A preliminary investigation in four families

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机构: [1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China [2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China [3]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, 1 Dongjiaominxiang, Beijing 100730, Peoples R China
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关键词: Allergic rhinitis Whole genome sequencing Gene expression profiling FLT1 VEGFB ITGA2 Rare variants

摘要:
Background: Despite the success of genome-wide association studies for allergic rhinitis (AR), no definitive causal variants have been identified, and a substantial portion of the heritability of the disease is yet to be discovered. Methods: Four families, each with at least 1 parent and one child suffering from dust mite (DM) AR, were recruited, and whole-genome sequencing was performed on samples from 9 eligible individuals from these families. Conjoint analysis was performed for existing gene expression profiling data in the literature and the whole genome sequencing data obtained for these individuals; for presence of family-specific variants segregating with AR and the pathways involved. Similar analyses were also performed with data obtained for 96 sporadic house dust mite (HDM) AR patients and 96 healthy controls. Results: Three rare variants in three genes (FLT1_c.603A > T; VEGFB_c.322A > C; and ITGA2_c.502thorn1G > A), which are involved in Focal Adhesion pathway, were identified in affected, but not unaffected, subjects in two families. VEGFB_c.322A > C and/or ITGA2_c.502thorn1G > A were further detected in all DM AR patients but not in any healthy individuals in 1 family; which was further investigated for members. The 3 identified variants were not found in any of the sporadic DM AR patients or healthy controls. Conclusion: Despite the relatively small sample size, this study has identified several potentially functional rare variants in AR candidate genes, and it provides a platform for future work in larger numbers of families and sporadic individuals for a better understanding of the genetic basis of AR.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 过敏 2 区 免疫学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 过敏 2 区 免疫学
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出版当年[2017]版:
Q1 ALLERGY Q1 IMMUNOLOGY
最新[2023]版:
Q2 ALLERGY Q2 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

第一作者:
第一作者机构: [1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China [2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China [3]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, 1 Dongjiaominxiang, Beijing 100730, Peoples R China
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通讯机构: [1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China [2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China [3]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, 1 Dongjiaominxiang, Beijing 100730, Peoples R China [*1]Beijing Institute of Otolaryngology No. 17, HouGouHuTong, DongCheng District, Beijing, 100005, China. [*2]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, No.1, Dongjiaominxiang, DongCheng District, Beijing 100730, PR China
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