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《工程(英文)》 >> 2023年 第26卷 第7期 doi: 10.1016/j.eng.2023.03.013

近十二年人类蛋白质N-糖基化的全基因组关联研究综述

a MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow 119991, Russia
b Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia

收稿日期: 2022-10-12 修回日期: 2023-03-22 录用日期: 2023-03-22 发布日期: 2023-05-19

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摘要

人类分泌的以及膜结合的大多数蛋白质都有共价连接的寡糖链或聚糖。糖基化影响着蛋白质的物理和化学性质及其生物功能。不难理解,蛋白质糖基化的改变与越来越多的人类疾病有关,而聚糖也越来越多地被视为潜在的治疗靶点、治疗药物的重要组成部分和生物标志物。尽管糖基化途径在生化方面被研究得很透彻,但人们对指导人类体内这些生化反应的细胞和组织特异性调节的基因网络知之甚少。由于缺乏对糖组变化的调控机制以及糖组与人类健康和疾病之间联系的详细了解,人类糖生物学的临床应用进展缓慢。人类遗传学和基因组学是用于提供人类体内糖生物学知识的两种亟待开发的工具,它们为剖析复杂性状的生物学特性提供了一种强大的数据驱动型不可知方法。本文总结了人类群体糖原组学的现状。在第1节中,简要概述了N-聚糖的结构组织;在第2节中,介绍了主要的血浆糖蛋白。接下来,在第3节中,总结、分类并归纳了当前N-糖基化全基因组关联研究(GWAS)的结果,这些研究提供了有关糖基化群体变异遗传调控的新知识。迄今为止,此类研究仅限于分析人体血浆N-糖组以及免疫球蛋白G和转铁蛋白的N-糖基化。虽然与不同组织和糖蛋白的大量糖组相比,这三种糖组只构成了相当有限的集合,但这三种糖组的研究确实可以提供有力的分析和归纳。然后,在第4节中讨论已确定位点中的基因,并在第5节中特别关注具有强支持作用的基因。最后,在第6节和第7节中介绍新发现的特殊案例,重点关注与人类蛋白质N-糖基化有关的基因变异的潜在作用机制和生物靶标。

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