中国女性全基因组拷贝数变异与初潮年龄的关联研究
发布时间：2019-06-11 04:12
【摘要】：初潮年龄(AAM)是由基因因素和环境因素共同影响的复杂性状。初潮是指青春期女生的第一次月经,通常发生在11岁至16岁之间。初潮是女生青春期的一个重要标志。青春期的发育年龄对个体在今后的生活上有很大的影响,包括对自身的,对社会的,也有对心理文化上的。由于青春期发育年龄很难准确界定,通常使用AAM来对其年龄早晚进行指示。AAM是许多病症的风险因子,例如忧郁症,精神障碍,骨质疏松症以及乳腺癌。当今有一些全基因组关联分析鉴定出一些与AAM有关联的基因和单核苷酸多态性(SNPs)。然而,这些方法得到的潜在基因还只是沧海一粟,这促使我们进一步寻找那些仍未被发现的,但对AAM有贡献率的遗传变异。随着现在拷贝数变异关联研究已经成为鉴定遗传基因位点的热潮,并且还没有关于初潮年龄表型与全基因组拷贝数变异的关联研究,因此这篇文章的主要目的是填补国内外这一学术空白。 拷贝数变异(CNV)是基因变异的一种类型,片段大小从1kb至数Mb不等。而拷贝数多态性(CNP)是指频率大于1%的CNV。CNV已经被证明是与某些人类复杂疾病相关联的。CNV在基因表达的总变异中比例占到20%。在正常健康的个体中,CNV在基因组中的广泛分布意味着CNV可能是表型多样性的一种驱动力。最近,我们实验室进行了骨质疏松症的全基因组拷贝数关联研究,并且鉴定出两个新的候选基因,UGT2B17和VPS13B。然而,至今还没有关于CNVs和AAM之间的关联研究,拷贝数变异对AAM所起的作用还不清楚。此研究中,我们在825个中国汉族女性人群中做了关于AAM的全基因组拷贝数变异的关联研究。研究采用Affymetrix GeneChip Human Mapping SNP 6.0的芯片,并随后在1728个美国白种人中对显著的结果进行了重复验证。我们发现位于染色体4q21.1的CNP10744在中国和美国人群中都达到显著水平,p值分别为0.017和0.010。在CNP10744区域有三个相关联的基因,淋巴细胞趋化因子(CXCL13),细胞周期蛋白G2(CCNG2),细胞周期蛋白I(CCNI)。它们对女性健康均有重要作用,也均作为AAM的潜在影响因子。比如说,高度表达于乳腺癌组织中,作用于类胰岛素生长因子结合蛋白的表达,与发育有重大关联的荷尔蒙相互作用,如雌激素、雄性激素、促性腺激素、下丘脑垂体激素和促肾上腺皮质激素等。
[Abstract]:Menarche age (AAM) is a complex trait affected by genetic and environmental factors. Menarche refers to the first menstruation of adolescent girls, usually between the ages of 11 and 16. Menarche is an important symbol of girls' adolescence. The developmental age of adolescence has a great influence on the future life of the individual, including on himself, on society and on psychology and culture. Because it is difficult to define the age of adolescence accurately, AAM is usually used to indicate its age sooner or later. AAM is a risk factor for many diseases, such as depression, mental disorder, osteoporosis and breast cancer. Today, some genome-wide association analysis has identified some genes and single nucleotide polymorphism (SNPs). Associated with AAM. However, the potential genes obtained by these methods are only a drop in the ocean, which leads us to look for genetic variants that have not yet been found but contribute to AAM. With the study of the association of copy number variation has become an upsurge in the identification of genetic loci, and there is no study on the association between menarche age phenotype and whole genome copy number variation. Therefore, the main purpose of this article is to fill in this academic gap at home and abroad. Copy number variation (CNV) is a type of gene variation, and the fragment size ranges from 1kb to Mb. Copy number polymorphism (CNP) refers to CNV.CNV whose frequency is more than 1%, which has been proved to be associated with some complex human diseases. CNV accounts for 20% of the total variation in gene expression. In normal and healthy individuals, the wide distribution of CNV in the genome means that CNV may be a driving force of phenotypic diversity. Recently, our laboratory conducted a study on the whole genome copy number association of osteoporosis, and identified two new candidate genes, UGT2B17 and VPS13B.. However, there is no study on the relationship between CNVs and AAM, and the role of copy number variation on AAM is not clear. In this study, we studied the association of whole genome copy number variation of AAM in 825 Chinese Han women. The chip of Affymetrix GeneChip Human Mapping SNP 6.0 was used, and the significant results were repeatedly verified in 1728 white people in the United States. We found that the CNP10744 located on chromosome 4q21.1 reached significant levels in Chinese and American populations, with p values of 0.017 and 0.010, respectively. There are three related genes in the CNP10744 region, lymphocytes chemokines (CXCL13), cell cycle protein G2 (CCNG2) and cell cycle protein I (CCNI). They play an important role in women's health and are potential influencing factors of AAM. For example, highly expressed in breast cancer tissues, acting on the expression of insulin-like growth factor binding proteins, has significant hormonal interactions with development, such as estrogen, androgen, gonadotropin, Hypothalamic pituitary hormones and corticotropin.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R394
本文编号：2497000
[Abstract]:Menarche age (AAM) is a complex trait affected by genetic and environmental factors. Menarche refers to the first menstruation of adolescent girls, usually between the ages of 11 and 16. Menarche is an important symbol of girls' adolescence. The developmental age of adolescence has a great influence on the future life of the individual, including on himself, on society and on psychology and culture. Because it is difficult to define the age of adolescence accurately, AAM is usually used to indicate its age sooner or later. AAM is a risk factor for many diseases, such as depression, mental disorder, osteoporosis and breast cancer. Today, some genome-wide association analysis has identified some genes and single nucleotide polymorphism (SNPs). Associated with AAM. However, the potential genes obtained by these methods are only a drop in the ocean, which leads us to look for genetic variants that have not yet been found but contribute to AAM. With the study of the association of copy number variation has become an upsurge in the identification of genetic loci, and there is no study on the association between menarche age phenotype and whole genome copy number variation. Therefore, the main purpose of this article is to fill in this academic gap at home and abroad. Copy number variation (CNV) is a type of gene variation, and the fragment size ranges from 1kb to Mb. Copy number polymorphism (CNP) refers to CNV.CNV whose frequency is more than 1%, which has been proved to be associated with some complex human diseases. CNV accounts for 20% of the total variation in gene expression. In normal and healthy individuals, the wide distribution of CNV in the genome means that CNV may be a driving force of phenotypic diversity. Recently, our laboratory conducted a study on the whole genome copy number association of osteoporosis, and identified two new candidate genes, UGT2B17 and VPS13B.. However, there is no study on the relationship between CNVs and AAM, and the role of copy number variation on AAM is not clear. In this study, we studied the association of whole genome copy number variation of AAM in 825 Chinese Han women. The chip of Affymetrix GeneChip Human Mapping SNP 6.0 was used, and the significant results were repeatedly verified in 1728 white people in the United States. We found that the CNP10744 located on chromosome 4q21.1 reached significant levels in Chinese and American populations, with p values of 0.017 and 0.010, respectively. There are three related genes in the CNP10744 region, lymphocytes chemokines (CXCL13), cell cycle protein G2 (CCNG2) and cell cycle protein I (CCNI). They play an important role in women's health and are potential influencing factors of AAM. For example, highly expressed in breast cancer tissues, acting on the expression of insulin-like growth factor binding proteins, has significant hormonal interactions with development, such as estrogen, androgen, gonadotropin, Hypothalamic pituitary hormones and corticotropin.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R394
【引证文献】
相关硕士学位论文 前1条
1 周小丹;蒙、汉族围绝经期妇女健康状况及生存质量调查研究[D];吉林大学;2012年
，本文编号：2497000
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