ANGELMAN SYNDROME, GENOMIC IMPRINTING AND GABAA RECEPTOR

γ-氨基丁酸（GABAA）受体α 5、β 3和γ 3 亚基基因在染色体15 q11-q13中组织成簇。这 染色体区域包含Angelman和Prader-Willi综合征基因座 这两种基因都受到父母的影响该区域还显示 异步DNA复制，这是印记的特征， 地区GABAA受体簇区域的噬菌体重叠群，其跨越 超过500 kb的DNA，几乎是完整的。这里建议隔离 来自50- 150 kb亚区的另外的基因，所述亚区位于β 3和 α 5亚基基因。在这个亚区，DNA复制发生在 在母体染色体上S期的开始，但延迟到 在父本染色体上的S末端。等位基因特异性模式 在这个相对较小的区域内的复制不同于 侧翼区显示与父本相反的模式， 在母体复制之前。从母体早期分离的基因 复制结构域的特征在于等位基因特异性 表达，并检查作为潜在的候选基因的天使 综合征本文还提出了一个鉴定DNA结构的研究方案 以及在建立添加/或维护中涉及的修改 母体早期复制区该域名将被筛选 DNA酶1超敏性位点，对于支架附着区（SAR）， 和等位基因特异性DNA甲基化。所有这些都很重要 染色质组织的特征可能是至关重要的机制， 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.