Cytognetic and Molecular Genetic Study of Transient Abnormal Myelopoiesis

短暂异常骨髓细胞生成的细胞遗传学和分子遗传学研究

• 批准号: 06454609
• 负责人: NIKAWA Norio
• 金额: $ 4.54万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454609/
• 关键词: Transient leukemia; Down syndrome; Breakpoint analysis; Positional cloning; Gene isolation; Chromosome inversion; Cosmid contig; Tumor-related gene; 遺伝子; 位置的単離; 染色体転座; 転座切断点; YAC; コンティグ; 一過性骨髄異常増殖症; 切断点クローン; STS

Transient abnormal myclopoiesis (TAM) is a leukemoid reaction occurring occasionally in Down syndrome (DS) newborn infants. It has been hypothesized that "disomic homozygosity" in 21-trisomic cells plays an important-role in the genesis of TAM,and the putative TAM gene was suggested to be mapped at a 21q11 region. We encountered a DS-associated TAM infant with a 47, XY,inv (21) (q11.1q22.13), +inv (21) (q11.1q22.13) karyotype. Based on another presumption that in this patient, the putative TAM gene is disrupted by the break, we tried to isolate a breakpoint DNA.FISH analysis with cosmid clones corresponding to various STS markers mapped at around 21q11.1-q11.2, we confirmed that the proximal breakpoint of the inv (21) was located between two STSs, G51E07 and D21S215, the latter locus being consistent to the previous tentative mapping. After construction of a cosmid contig encompassing between the 2 markers, we have isolated a cosmid clone corresponding to the proximal breakpoint of the inversion. This breakpoint was located nearby a previously identified duplicated-region that is homologous to the sequence at 21q22.1. The isolated cosmid clone is useful for analysis of other TAM patients and for a search for a transcript at or flanking the breakpoint.

短暂性异常骨髓生成（TAM）是一种类白血病反应，偶尔发生在唐氏综合征（DS）新生儿。21-三体细胞中的“二体纯合性”在TAM的发生中起重要作用，推测TAM基因定位于21 q11区域。我们遇到了一个DS相关的TAM婴儿，核型为47，XY，inv（21）（q11.1q22.13），+inv（21）（q11.1q22.13）。基于另一个假设，即在该患者中，假定的TAM基因被断裂破坏，我们试图分离断裂点DNA。用对应于定位在21q11.1-q11.2附近的各种STS标记的粘粒克隆进行FISH分析，我们证实inv（21）的近端断裂点位于两个STS，G51 E07和D21 S215之间，后一个位点与先前的试验性作图一致。在构建包含2个标记之间的粘粒重叠群之后，我们分离了对应于倒位的近端断点的粘粒克隆。该断裂点位于先前鉴定的与21q22.1序列同源的重复区域附近。分离的粘粒克隆可用于其他TAM患者的分析和用于在断点处或断点侧翼的转录本的搜索。

项目成果

Ohta T,Nakano M,Tsujita T,Abe K,Osoegawa K,Yamagata T,Yoshiura K,Jinno Y,Soeda E,Niikawa N: "Isolation of a cosmid clone corrsponding to a region of the inv (21) breakpoint in a patient with transient abnormal myelopoicsis." Am J Hum Genet. 58. 544-550 (1

Ohta T、Nakano M、Tsujita T、Abe K、Osoekawa K、Yamagata T、Yoshiura K、Jinno Y、Soeda E、Niikawa N：“在患者体内分离与 inv (21) 断点区域相对应的粘粒克隆

新川詔夫: "特殊な腫瘍関連遺伝子のポジショナルクローニング:一過性骨髄異常増殖症と多発性外骨腫遺伝子" 臨床病理. 44. 13-18 (1996)

Akio Shinkawa：“特殊肿瘤相关基因的位置克隆：短暂性骨髓发育不良和多发性外生骨疣基因”《临床病理学》44. 13-18 (1996)。

Ohta T, Nakano M, Tsujita T, Abe K, Osoegawa K,Yamagata T, Yoshiura K, Jinno Y, Soeda E, Niikawa N: "Isolation of a cosmid clone corresponding to a region of thr inv(21)breakpoint in a patient with transient abnormal myelopoiesis." American Journal of Hum

Ohta T、Nakano M、Tsujita T、Abe K、Osoekawa K、Yamagata T、Yoshiura K、Jinno Y、Soeda E、Niikawa N：“分离与患者体内 thr inv(21) 断点区域相对应的粘粒克隆

OHTA,T.,NAKANO,M.,ET AL.: "ISOLATION OF A COSMID CLONE CORRESPONDING TO A REGION OF THE INV (21) BREAKPOINT IN A PATIENT WITH TRANSIET ABNORMAL MYELOPOIESIS" AMERICAN JOURNAL OF HUMAN GENETICS. IN PRESS. (1996)

OHTA,T.,NAKANO,M.,等人：“在患有短暂性异常骨髓生成​​的患者中分离与 INV (21) 断点区域相对应的粘粒克隆”美国人类遗传学杂志。