拼接部位和de novo变体可能会导致PLCG2相关的免疫失调与寒冷的疹
Sophia R Chou1, Alexis C Bailey1, Kathleen Baysac1
1Translational Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Md.
The Journal of allergy and clinical immunology
|December 12, 2024
概括
基因分析确定了PLCG2中的新拼接部位和de novo删除,导致PLCγ2相关的免疫失调与寒冷的疹 (PLAID-CU). 这些PLAID-CU遗传病变可以使用cDNA测序来检测.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 脂酶Cγ2 (PLCγ2) 对于造血细胞中信号传递至关重要.
- 在PLCG2的遗传变异导致PLCγ2相关的免疫失调 (PLAID).
- 带有寒冷疹的PLAID (PLAID-CU) 涉及具有温度依赖活性的PLCG2框架内删除.
研究的目的:
- 确定PLAID的遗传原因.
- 将PLCG2的RNA测序与全基因组测序相结合.
主要方法:
- 研究了9名抗体缺乏和感冒敏感的试验者,以及2名PLAID-CU患者和3名对照.
- 在PLCG2的cDNA和全基因组测序上进行了Illumina测序.
- 在细胞系统中过度表达新的PLCG2转录和量化ERK酸化.
主要成果:
- 确定了两名具有新PLCG2替代转录的探针,其中包括框架内删除.
- 一个试验对象发生了导致异构体18-19被删除的拼接部位突变;另一个试验对象出现了异构体19-22的新增删除.
- 这些被删除的转录在DT40细胞中的过度表达,在B细胞受体交叉连接后损害了ERK酸化.
结论:
- 在PLCG2中,de novo删除和拼接位突变可以导致PLAID-CU,以及已知的基因组删除.
- 基于cDNA的测序对于识别这些多样化的PLCG2遗传病变是有效的.
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