ANGELMAN SYNDROME, GENOMIC IMPRINTING AND GABAA RECEPTOR

γ-氨基丁酸受体α5、β3和γ3 亚单位基因在染色体15q11-q13上以簇的形式组织。这 染色体区域包含Angelman和Prader-Willi综合征基因座 它们都受到父母印记的影响。此区域还会显示 非同步DNA复制，这是印记的特征 地区。GABAA受体簇区的一个噬菌体重叠群，它跨越 超过500kb的DNA，已经接近完成。这里建议分离出 位于Beta3和Beta3之间的50-150kb亚区的其他基因 α5亚基基因。在这一次区域，DNA复制发生在 在母体染色体上的S阶段的开始，但被推迟到 S在父亲染色体上的末端。等位基因特异性的模式 在这个相对较小的域中的复制与 与父系呈现相反图案的侧翼区域 在母体复制之前。从母体早期分离的基因 复制结构域将根据特定的等位基因来表征 表达并被检测为安吉曼的潜在候选基因 综合症。还提出了一项鉴定dna结构的研究计划。 以及在建立添加/或维护过程中涉及的修改 母体早期复制结构域。将对该域进行筛选 脱氧核糖核酸酶L过敏部位，支架附着区， 以及等位基因特异的DNA甲基化。所有这些都很重要 染色质组织的特征可能对这一机制至关重要 父母的印记。

The gamma-aminobutyric acid (GABAA) receptor alpha5, beta3 and gamma3 subunit genes are organized as a cluster in chromosome 15q11-q13. This chromosomal region contains the Angelman and Prader-Willi syndrome loci which are both subject to parental imprinting. This region also displays asynchronous DNA replication which is a characteristic of imprinted regions. A phage contig of the GABAA receptor cluster region, which spans more than 500kb of DNA, is nearly complete. It is proposed here to isolate additional genes from a 50-150kb subregion located between the beta3 and alpha5 subunit genes. In this subregion, DNA replication occurs at the beginning of S phase on the maternal chromosome but is delayed until the end of S on the paternal chromosome. The pattern of allele-specific replication within this relatively small domain is distinct from that of the flanking regions which display the opposite pattern with paternal before maternal replication. The genes isolated from the maternal early replicating domain will be characterized with respect to allele-specific expression and examined as potential candidate genes for the Angelman syndrome. A program of study is also proposed to identify DNA structures and modifications which are involved in establishing add/or maintaining the maternal early replication domain. The domain will be screened for sites of DNase l hypersensitivity, for scaffold attachment regions (SARs), and for allele-specific DNA methylation. All of these are important features of chromatin organization which could be crucial to the mechanism of parental imprinting.