权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular and clinical research of the growth genes on the sex chromosomes

性染色体生长基因的分子和临床研究

基本信息

批准号：
07457184
负责人：
MATSUO Nobutake
金额：
$ 4.1万
依托单位：
Keio University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457184/
关键词：
Sex chromosome Growth gene Pseudoautosomal region Y-specific region Gene cloning Yeast artificial chromosome Cosmid Short stature

项目摘要

<Pseudoautosomal growth gene>We have localized a pseudoautosomal growth gene (P-growth gene) to a roughly 350kb region between DXYS60 and DXYS15 on the basis of genotype-phenotype correlations in 16 patients with partial monosomy of the pseudoautosomal region, and constructed a cosmid contig spanning the critical region. Positional cloning was carried out with c-DNA selection and exon trapping, successfully isolating a novel gene. This gene, termed SHOX,contained a homeobox domain and consisted of five exons. Mutational analysis of the SHOX gene was performed for a total of 91 patients with idiopathic short stature, and identified a nonsense mutation that was co-segregated with short stature in a particular family. Thus, we have cloned a novel homeobox gene, SHOX,that is an excellent candidate for the P-growth gene. This study was carried out as a collaboration work with Dr.Gudrum Rappold's group, Heidelberg University.<Y-specific growth gene>We have assigned a Y-specific growth gene (Y-growth gene) to a roughly 1 Mb region between DYS11 and DYS246 by genotype-phenotype correlations in 13 patients with partial deletion of the Y chromosome long arm, and constructed a yeast artificial chromosome contig which almost spans the critical region. We have also clarified that a novel gene UTY controlling mitosis is present on the critical region, suggesting that DUTY is a candidate for the Y-growth gene. Furthermore, we have proposed that the Y-growth gene controls the sex steroid-independent childhood growth pattern and increases the male final height by 7-10cm independently of the effect of sex steroids. In support of this notion, we have identified eight male patients whose growth pattern is consistent with the Y-growth gene being mutated. This study was carried out as a collaboration work with Dr.Yutaka Nakahori's group, Tokyo University.

<假常染色体生长基因>我们在16例假常染色体部分单体患者的基因型-表型相关性的基础上，将一个假常染色体生长基因（p -生长基因）定位在DXYS60和DXYS15之间约350kb的区域，并构建了跨越该关键区域的cosmid contig。利用c-DNA选择和外显子捕获技术进行定位克隆，成功分离到一个新基因。这个基因被称为SHOX，包含一个同源盒结构域，由五个外显子组成。对91例特发性身材矮小的患者进行了SHOX基因的突变分析，并在一个特定的家庭中发现了一个与身材矮小共分离的无义突变。因此，我们克隆了一个新的同源盒基因SHOX，这是p生长基因的一个很好的候选者。这项研究是与海德堡大学古德鲁姆·拉波尔德博士的小组合作进行的。我们在13例Y染色体长臂部分缺失的患者中，通过基因型-表型相关性将一个Y特异性生长基因（Y生长基因）定位在DYS11和DYS246之间约1 Mb的区域，构建了一个几乎跨越该关键区域的酵母人工染色体组群。我们还澄清了一个控制有丝分裂的新基因UTY存在于关键区域，这表明DUTY是y生长基因的候选基因。此外，我们提出y生长基因控制着不依赖于性类固醇的童年生长模式，并使男性最终身高增加7-10cm，而不依赖于性类固醇的影响。为了支持这一观点，我们已经确定了8名男性患者，他们的生长模式与y型生长基因突变一致。这项研究是与东京大学yutaka Nakahori博士的团队合作进行的。