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

为了研究下丘脑-垂体-性腺轴遗传背景与青春期发病的关系，我们选择了合适的促性腺激素释放激素（GnRH）、促黄体生成素（LH）、促卵泡激素（FSH）、HSD17B3、CYP3A4、CYP17、CYP1B1和CYP1A2基因的单核苷酸多态性（snp）。这些基因的SNP信息来自两个SNP数据库（JSNP: http://snp.ims.u-tokyo.ac.jp/和Ensemble Project: 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snp。我们构建了正向引物和反向引物来扩增snp，并使用引物3 （http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi）进行分析。然后，我们计算基因中每个snp的r2和D'，以选择候选snp进行单倍型分析。我们决定选择GnRH基因中的3个snp、LHB基因中的3个snp、FSHB基因中的4个snp、HSD17B3基因中的9个snp、cyp17基因中的8个snp、CYP1B1基因中的5个snp和CYP1A2基因中的5个snp。我们无法在CYP 3A4基因中选择任何snp，因为每个snp之间具有很高的相关性。利用基因中的这些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.