| Project/Area Number |
09470185
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
MATSUO Nobutake Keio University, Pediatrics, Professor, 医学部, 教授 (50173802)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Seiji Keio University, Pediatrics, Assistant Professor, 医学部, 講師 (80146638)
深見 真紀 慶應義塾大学, 医学部, 助手 (40265872)
室谷 浩二 慶應義塾大学, 医学部, 助手 (60239556)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥7,900,000 (Direct Cost: ¥7,900,000)
|
|---|
| Keywords | X chromosome / Mental retardation gene / Non-specific MR / Syndromic MR / X-inactivation / Positional cloning / Exon trapping / Homologous genes |
|---|
| Research Abstract |
<MRX gene at Xp22.3>
We localized this gene for mental retardation (MRX) to a roughly 200 kb region, on the basis of genotype-phenotype correlations in 15 male patients with various types of nullisomy for Xp22.3. Then, we constructed a cosmiod/PAC contig covering the critical region, and identified a novel gene by means of the positional cloning method. This gene is widely expressed including the central nervous system, and is associated with a pseudogene on the Y chromosome. Furthermore, we found random X-inactivation pattern in four mentally normal females with a cryptic deletion at Xp22.3 encompassing the critical region, thereby obtaining genetic evidence for the MRX gene escaping X-incativation.
<MRX gene at Xp2l.3>
We assigned this gene to an approximately 2 Mb region between DXS7182 and DXS7188, on the basis of genotype-phenotype correlations in four families with mental retardation. In addition, we found random X-inactivation pattern in four mentally impaired females with a small deletion at Xp2l.3 encompassing the critical region, providing genetic evidence for the MRX gene being subject to X-incativation.
<MLS gene at Xp22>
We identified random X-inactivation pattern in a female infant with microphthalmia with linear skin defects (MLS) and 45, X/46, X.r(X)(p22q21)/46, X,del(X)(p22). This suggests that functional nullisomy for the MLS gene in cells with inactive normal X chromosomes is responsible for the development of MLS phenotype including mental retardation.
|
