中國女性全基因組拷貝數(shù)變異與初潮年齡的關(guān)聯(lián)研究
發(fā)布時間：2019-06-11 04:12
【摘要】：初潮年齡(AAM)是由基因因素和環(huán)境因素共同影響的復(fù)雜性狀。初潮是指青春期女生的第一次月經(jīng),通常發(fā)生在11歲至16歲之間。初潮是女生青春期的一個重要標(biāo)志。青春期的發(fā)育年齡對個體在今后的生活上有很大的影響,包括對自身的,對社會的,也有對心理文化上的。由于青春期發(fā)育年齡很難準(zhǔn)確界定,通常使用AAM來對其年齡早晚進(jìn)行指示。AAM是許多病癥的風(fēng)險因子,例如憂郁癥,精神障礙,骨質(zhì)疏松癥以及乳腺癌。當(dāng)今有一些全基因組關(guān)聯(lián)分析鑒定出一些與AAM有關(guān)聯(lián)的基因和單核苷酸多態(tài)性(SNPs)。然而,這些方法得到的潛在基因還只是滄海一粟,這促使我們進(jìn)一步尋找那些仍未被發(fā)現(xiàn)的,但對AAM有貢獻(xiàn)率的遺傳變異。隨著現(xiàn)在拷貝數(shù)變異關(guān)聯(lián)研究已經(jīng)成為鑒定遺傳基因位點(diǎn)的熱潮,并且還沒有關(guān)于初潮年齡表型與全基因組拷貝數(shù)變異的關(guān)聯(lián)研究,因此這篇文章的主要目的是填補(bǔ)國內(nèi)外這一學(xué)術(shù)空白。 拷貝數(shù)變異(CNV)是基因變異的一種類型,片段大小從1kb至數(shù)Mb不等。而拷貝數(shù)多態(tài)性(CNP)是指頻率大于1%的CNV。CNV已經(jīng)被證明是與某些人類復(fù)雜疾病相關(guān)聯(lián)的。CNV在基因表達(dá)的總變異中比例占到20%。在正常健康的個體中,CNV在基因組中的廣泛分布意味著CNV可能是表型多樣性的一種驅(qū)動力。最近,我們實驗室進(jìn)行了骨質(zhì)疏松癥的全基因組拷貝數(shù)關(guān)聯(lián)研究,并且鑒定出兩個新的候選基因,UGT2B17和VPS13B。然而,至今還沒有關(guān)于CNVs和AAM之間的關(guān)聯(lián)研究,拷貝數(shù)變異對AAM所起的作用還不清楚。此研究中,我們在825個中國漢族女性人群中做了關(guān)于AAM的全基因組拷貝數(shù)變異的關(guān)聯(lián)研究。研究采用Affymetrix GeneChip Human Mapping SNP 6.0的芯片,并隨后在1728個美國白種人中對顯著的結(jié)果進(jìn)行了重復(fù)驗證。我們發(fā)現(xiàn)位于染色體4q21.1的CNP10744在中國和美國人群中都達(dá)到顯著水平,p值分別為0.017和0.010。在CNP10744區(qū)域有三個相關(guān)聯(lián)的基因,淋巴細(xì)胞趨化因子(CXCL13),細(xì)胞周期蛋白G2(CCNG2),細(xì)胞周期蛋白I(CCNI)。它們對女性健康均有重要作用,也均作為AAM的潛在影響因子。比如說,高度表達(dá)于乳腺癌組織中,作用于類胰島素生長因子結(jié)合蛋白的表達(dá),與發(fā)育有重大關(guān)聯(lián)的荷爾蒙相互作用,如雌激素、雄性激素、促性腺激素、下丘腦垂體激素和促腎上腺皮質(zhì)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.
【學(xué)位授予單位】：湖南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R394
本文編號：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.
【學(xué)位授予單位】：湖南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R394
【引證文獻(xiàn)】
相關(guān)碩士學(xué)位論文 前1條
1 周小丹;蒙、漢族圍絕經(jīng)期婦女健康狀況及生存質(zhì)量調(diào)查研究[D];吉林大學(xué);2012年
，本文編號：2497000
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