Relationship of genetic diversity of hypothalamo-pituitary-gonadal axis and puberatal onset

下丘脑-垂体-性腺轴遗传多样性与青春期发病的关系

• 批准号: 15591077
• 负责人: ITO Yoshiya
• 金额: $ 1.73万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591077/
• 关键词: Pubertal onset; genetic control; SNP; Haplotype; steroidogenesis

In order to investigate the association of genetic background of hypothalamo-pituitary-gonadal axis to pubertal onset, we selected appropriate single nucleotide polymorphisms (SNPs) in gonadotropin releasing hormone (GnRH), luteinizing hormone, (LH), follicle stimulating hormone (FSH), HSD17B3, CYP3A4, CYP17, CYP1B1, and CYP1A2 genes. Information on SNPs of those genes are collected from two SNP databases (JSNP : http://snp.ims.u-tokyo.ac.jp/ and Ensemble Project : http://www.ensembl.org/Homo_sapiens/). There are 10 SNPs in the GNRH1 gene, 4 SNPs in the LHB gene, 6 SNPs in the FSHB gene, 12 SNPs in the HSD17B3 gene, 7 SNPs in the CYP1A2 gene, 8 SNPs in the CYP3A4 gene, 6 SNPs in the CYP1B1 gene, 8 SNPs in the CYP3A4 gene, and 12 SNPs in the CYP17A1 gene. We constructed forward and backward primer to amplify the SNPs and analyze alleies using Primer 3 (http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi). Then, we calculated r2 and D' in each SNPs in the gene to select candidate SNPs for haplotype analysis. We decided to select 3 SNPs in the GnRH gene, 3 SNPs in the LHB gene, 4 SNPs in the FSHB gene, 9 SNPs in the HSD17B3 gene, 8 SNPS in the CYP17gene, 5 SNPs in the CYP1B1 gene, and 5 SNPS in the CYP1A2 gene. We could not select any SNPs in the CYP 3A4 gene because of high correlation between each SNPs.Using these SNPs in the genes, we have to construct haplotype to clarify genetic control of pubertal onset.

为了探讨下丘脑-垂体-性腺轴遗传背景与青春期开始的关系，我们选择了促性腺激素释放激素（GnRH）、促黄体生成激素（LH）、促卵泡激素（FSH）、HSD 17 B3、CYP 3A 4、CYP 17、CYP 1B 1和CYP 1A 2基因的单核苷酸多态性（SNP）。从两个SNP数据库（JSNP：http://snp.ims.u-tokyo.ac.jp/和Ensemble Project：http：//www.ensembl.org/Homo_sapiens/）收集关于这些基因的SNP的信息。GNRH 1基因中有10个SNP，LHB基因中有4个SNP，FSHB基因中有6个SNP，HSD 17 B3基因中有12个SNP，CYP 1A 2基因中有7个SNP，CYP 3A 4基因中有8个SNP，CYP 1B 1基因中有6个SNP，CYP 3A 4基因中有8个SNP，CYP 17 A1基因中有12个SNP。我们构建了正向和反向引物来扩增SNP，并使用引物3（http：//www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi）分析等位基因。然后，我们计算基因中每个SNP的r2和D'，以选择用于单倍型分析的候选SNP。我们决定在GnRH基因中选择3个SNP，在LHB基因中选择3个SNP，在FSHB基因中选择4个SNP，在HSD 17 B3基因中选择9个SNP，在CYP 17基因中选择8个SNP，在CYP 1B 1基因中选择5个SNP，在CYP 1A 2基因中选择5个SNP。我们无法在该基因中选择任何SNPs，因为每个SNPs之间的高度相关性，我们必须利用这些基因中的SNPs构建单倍型，以阐明青春期开始的遗传控制。