Investigation of the imprinted domain located at the chromosomal deletion associated with Prader-Willi syndrome

位于与普瑞德-威利综合征相关的染色体缺失处的印记结构域的研究

• 批准号: 13670858
• 负责人: KUBOTA Takeo
• 金额: $ 2.43万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670858/
• 关键词: imprinting; domain; methylation; Prader-Willi Syndrome; methylation-specific PCR; translocation; deletion; mono allelic; 染色体; 欠失; DNA; 遺伝子

Prader-Willi syndrome (PWS) is one of the famous diseases that are characterized by obesity and mental retardation. Most of the patients share the same chromosome deletion at 15q11-q13. The deletion always occurs on the paternal chromosome, suggesting involvement of the genomic imprinting. Although several imprinted genes has been discovered within this deletion, it has yet not known whether some additional imprinted genes exist outside of the deletion, "an imprinted domain".We found a severe PWS patient with a large chromosome 15 deletion and found that its distal breakpoint was located approximately 20kb more telomeric from the common breakpoint of that of the usual PWS patient. Using the cultured cells from this severe patient, we investigated genes (ESTs) mapped in the extra deleted whether some of these are imprinted. As a result, we found that none of these genes was imprinted at least in the lymphoblast cells. Therefore, we could not obtain the proof that indicates the imprinted domain was larger than thought. These above data have recently been published in Clinical Genetics.

普瑞德威利综合征（PWS）是一种以肥胖和智力低下为特征的著名疾病。大多数患者在 15q11-q13 处有相同的染色体缺失。缺失总是发生在父本染色体上，表明涉及基因组印记。虽然在这个缺失中发现了几个印记基因，但目前还不知道在该缺失之外是否还存在一些额外的印记基因，即“印记域”。我们发现了一名严重的PWS患者，其15号染色体存在大面积缺失，并发现其远端断点位于比普通 PWS 患者的常见断点多约 20kb 的端粒处。使用来自该重症患者的培养细胞，我们研究了额外删除中映射的基因（EST）是否其中一些被印记。结果，我们发现这些基因至少没有被印记在淋巴母细胞中。因此，我们无法获得印迹域比想象的更大的证据。上述数据最近发表在《临床遗传学》杂志上。

项目成果

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Inoue K 等人：“与 Pelizaeus-Merzbacher 病相关的 PLP1 重复的产前间期 FISH 诊断”Prenat Diagn。

Wakui K, Kubota T, et al.: "Familial 14-Mb interstitial deletion at 21q11.2-q21.3 and..."J Hum Genet. 47. 511-516 (2001)

Wakui K、Kubota T 等人：“21q11.2-q21.3 处的家族性 14-Mb 间质缺失和……”J Hum Genet。

Akahoshi K, et al.: "Hyperpigmentation is related to excess copy of P genes a patient with duplication of 15q11.2-q14"Am J Med Genet. 104. 299-302 (2001)

Akahoshi K 等人：“色素沉着过度与 15q11.2-q14 重复患者的 P 基因拷贝过多有关”Am J Med Genet。

Matsumura M, Kubota T, et al.: "Severe Prader-Willi syndrome"Clinical Genet. 63. 79-81 (2003)

Matsumura M、Kubota T 等：“严重 Prader-Willi 综合征”临床基因。

Kanegane H, et al.: "Clinical and mutational characteristics of X-linked agammaglobulinemia"J Allerg Clin Immunol. 108. 1012-1020 (2001)

Kanegane H 等人：“X 连锁无丙种球蛋白血症的临床和突变特征”J Allerg Clin Immunol。