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Mom1基因座候选基因的人类同源物,即分泌型II型磷脂酶A2(PLA2S-II),定位于1p35 - 36.1/D1S199。

Human homologue of a candidate for the Mom1 locus, the secretory type II phospholipase A2 (PLA2S-II), maps to 1p35-36.1/D1S199.

作者信息

Praml C, Savelyeva L, Le Paslier D, Siracusa L D, Buchberg A M, Schwab M, Amler L C

机构信息

Department of Cytogenetics-0130, German Cancer Research Center, Heidelberg, Germany.

出版信息

Cancer Res. 1995 Dec 1;55(23):5504-6.

PMID:7585622
Abstract

Mice heterozygous for the dominant Min mutation in their Apc gene develop multiple intestinal neoplasia. Analogously, family members from familial adenomatous polyposis kindreds inheriting mutations in their human APC homologue develop a similar phenotype. Quantitative trait loci studies have identified the Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic variability in polyp number found among inbred mouse strains. The secretory type II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carrying the Min mutation has been proposed to account for an increased polyp number compared to mice without the Pla2s-II mutation. In this study, we have mapped the chromosomal position of the human homologue of Pla2s-II. We have identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized one of them by fluorescence in situ hybridization to the border between 1p35 and 1p36.1. The presence of the microsatellite marker D1S199 in all three clones integrates PLA2S-II into different genetic maps. This highly polymorphic CA repeat D1S199 has previously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of the Pla2s-II/Mom1 locus might be related to human colorectal cancer.

摘要

携带Apc基因显性Min突变的杂合子小鼠会发生多发性肠道肿瘤。类似地,家族性腺瘤性息肉病家族中继承人类APC同源基因突变的家庭成员也会出现类似的表型。数量性状基因座研究确定了Mom1基因座(Min-1修饰基因),它负责近交系小鼠品系中息肉数量的部分遗传变异性。分泌型II型磷脂酶[非胰腺磷脂酶A2(II型磷脂酶A2或磷脂酶A2-II)]已被证明是Mom1的候选基因,并且有人提出,携带Min突变的小鼠中磷脂酶A2-II的突变可解释与无磷脂酶A2-II突变的小鼠相比息肉数量增加的原因。在本研究中,我们绘制了磷脂酶A2-II人类同源基因的染色体位置。我们鉴定出3个携带PLA2S-II的大型酵母人工染色体,并通过荧光原位杂交将其中一个定位于1p35和1p36.1之间的边界。所有3个克隆中均存在微卫星标记D1S199,这将PLA2S-II整合到了不同的遗传图谱中。我们之前已证明,这种高度多态的CA重复序列D1S199可在48%的散发性结直肠癌肿瘤中鉴定出杂合性缺失,这表明磷脂酶A2-II/Mom1基因座的人类同源基因可能与人类结直肠癌有关。

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