Identification of genes involved in genomic imprinting and intrauterine growth

鉴定参与基因组印记和子宫内生长的基因

基本信息

批准号：
11470507
负责人：
NIIKAWA Norio
金额：
$ 9.22万
依托单位：
Department of Human Genetics, Nagasaki 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：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Identification of Silver-Russell syndrome (SRS) responsible region and candidate gene analysis : Allelotype analysis of one SRS patient with abnormal karyotype using microsatellite markers revealed that a 7p13-q11 segment showed biallelism while the remaining region of chromosome 7 showed only maternal alleles. The results indicated that the putative SRS region is confined to 7q11-qter. Although two genes on chromosohie 7, GRB10 and MEST, have become a candidate gene for SRS, results of an imprinting analysis of the gents using hybrid cell panels and methylation analysis did not support the hypothesis.Construction of a 1.2-Mb PAC contig (physical and transcription map) : To confirm an imprinted gene cluster on 7q32, such a contig between D7S530 wAD7S649 including MEST was constructed. It contains 70 novel STSs, 9 novel genes, and 6 known genes.Identification of imprinted genes at 7q32 : Among the genes mapped at the contig, the gene^ to be or not to be imprinted included MEST, COPG2, COPG2TT1 (CfTl), KIAA0265, CPA3, CPA1, mdTSGA14. Both MEST and COPG2IT1 are paternally expressed, while CPA3 is maternally expressed Although COPG2 was thought to be paternally expressed, it is actually biallelically expressed. However, a novel EST (COPG2IT1), the antisense transcript from COPG2-intron 20, showed paternally monoallelic expression in fetal tissues. CPA3 showed partially imprinted in the fetal heart, kidney and lung, and the adult prostate, whereas it loses imprinting partially or completely in lymphoblastoid cells. The findings that COPG2, KIAA 0265, CPA 1 and TSGA14 all showed biallelic expression did not support that their imprinting. These findings, especially the absence of imprinting of COPG2 and TSGA14 which are located nearby MEST suggest that the 7q32 region is not strictly controlled as an imprinting domain but controlled by independent imprinting signals.

使用微卫星标记物对一名SRS异常核型患者的过度型分析鉴定银 - 鲁塞尔综合征（SRS）负责区域和候选基因分析：7p13-Q11段表明，7p13-Q11段显示双重链球菌，而7P13-Q11则显示了染色体的其余区域，而染色体的其余区域仅显示出母亲的其他等位基因。结果表明，假定的SRS区域仅限于7q11-Qter。尽管铬糖7，GRB10和MEST上的两个基因已成为SRS的候选基因，但使用杂交细胞板和甲基化分析对Gent进行了烙印的结果并不支持假设。构建1.2-Mb Pac PAC COTIG（物理和转录图）：确认在7q32上的Indrign 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 cont 7 contrance contig and 7 cont 7 contrancy n contruds w。 Mest构建了。它包含70个新颖的STS，9个新基因和6个已知基因。在第7季度识别印迹基因：在重叠群映射的基因中，基因^是或不被刻印的基因包括Mest，COPG2，COPG2，COPG2TT1（CFTL），CFTL），KIAA0265，CPA3，CPA3，CPA3，CPA3，CPAGA，cpa11，MDDSGA14。 MEST和COPG2IT1均以亲子态表达，而CPA3则表达了母体表达，尽管认为COPG2被认为是亲子表达的，但实际上是双向表达的。然而，来自COPG2-IntRON 20的反义转录本的新型EST（COPG2IT1）在胎儿组织中显示了单相关的亲核表达。 CPA3在胎儿心脏，肾脏和肺部以及成年前列腺中部分印象深刻，而在淋巴母细胞细胞中部分或完全失去印迹。 COPG2，KIAA 0265，CPA 1和TSGA14的发现均显示出双重表达，这不支持它们的烙印。这些发现，尤其是位于附近的COPG2和TSGA14的印迹，这表明7q32区域并非严格控制为烙印域，而是由独立的印记信号控制。