| Project/Area Number |
07457184
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Keio University School of Medicine |
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Principal Investigator |
MATSUO Nobutake Keio University, Pediatrics, Professor, 医学部, 教授 (50173802)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAMI Maki Keio University, Pediatrics, Assistant, 医学部, 助手 (40265872)
MUROYA Koji Keio University, Pediatrics, Assistant, 医学部, 助手 (60239556)
ANZO Makoto Keio University, Pediatrics, Assistant, 医学部, 助手 (80193100)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Sex chromosome / Growth gene / Pseudoautosomal region / Y-specific region / Gene cloning / Yeast artificial chromosome / Cosmid / Short stature |
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| Research Abstract |
<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.
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