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

为了探讨下丘脑-垂体-性腺轴的遗传背景与青春期发病的关系，我们选择了促性腺激素释放激素(GnRH)、黄体生成素(LH)、卵泡刺激素(FSH)、Hsd17b3、CYP3A4、CYP17、CYP1B1和CYP1A2基因的适当单核苷酸多态性(SNPs)。关于这些基因的SNP的信息来自两个SNP数据库(JSNP：http://snp.ims.u-tokyo.ac.jp/和集合项目：http://www.ensembl.org/Homo_sapiens/).GNRH1基因有10个SNPs，LHb基因有4个SNPs，Fshb基因有6个SNPs，Hsd17b3基因有12个SNPs，CYP1A2基因有7个SNPs，CYP3A4基因有8个SNPs，CYP1B1基因有6个SNPs，CYP3A4基因有8个SNPs，CYP17A1基因有12个SNPs。我们构建了正向和反向引物来扩增SNPs，并用Primer 3(http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi).进行了小巷分析然后，我们计算基因中每个SNPs的R2和D‘，以选择用于单倍型分析的候选SNPs。我们决定选择GnRH基因中的3个SNPs、LHb基因中的3个SNPs、Fshb基因中的4个SNPs、Hsd17b3基因中的9个SNPs、CYP17基因中的8个SNPs、CYP1B1基因中的5个SNPs和CYP1A2基因中的5个SNPs。由于CYP 3A4基因中每个SNP之间的高度相关性，我们不能选择任何一个SNP，利用这些SNP，我们必须构建单倍型来阐明青春期发病的遗传控制。

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.