小鼠肠道肿瘤形成的Mom1修饰基因的候选基因的遗传评估。
Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice.
作者信息
Gould K A, Luongo C, Moser A R, McNeley M K, Borenstein N, Shedlovsky A, Dove W F, Hong K, Dietrich W F, Lander E S
机构信息
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.
出版信息
Genetics. 1996 Dec;144(4):1777-85. doi: 10.1093/genetics/144.4.1777.
Abstract
As genetic mapping of quantitative trait loci (QTL) becomes routine, the challenge is to identify the underlying genes. This paper develops rigorous genetic tests for evaluation of candidate genes for a QTL, involving determination of allelic status in inbred strains and fine-structure genetic mapping. For the Mom1 modifier of intestinal adenomas caused by ApcMin, these tests are used to evaluate two candidate genes: Pla2g2a, a secretory phospholipase, and Rap1GAP, a GTPase activating protein. Rap1GAP passes the first test but is excluded by a single fine-structure recombinant. Pla2g2a passes both tests and is a strong candidate for Mom1. Significantly, we also find that ApcMin-induced adenomas remain heterozygous for the Mom1 region, consistent with Mom1 acting outside the tumor lineage and encoding a secreted product.
摘要
随着数量性状基因座（QTL）的遗传定位变得常规化，面临的挑战是鉴定潜在基因。本文开发了严格的遗传学测试来评估QTL的候选基因，包括确定近交系中的等位基因状态和精细结构遗传定位。对于由ApcMin引起的肠道腺瘤的Mom1修饰基因，这些测试用于评估两个候选基因：分泌型磷脂酶Pla2g2a和GTP酶激活蛋白Rap1GAP。Rap1GAP通过了第一项测试，但被一个单一的精细结构重组体排除。Pla2g2a通过了两项测试，是Mom1的有力候选基因。值得注意的是，我们还发现ApcMin诱导的腺瘤在Mom1区域保持杂合状态，这与Mom1在肿瘤谱系外起作用并编码一种分泌产物一致。
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本文引用的文献
1
Mom1 is a semi-dominant modifier of intestinal adenoma size and multiplicity in Min/+ mice.Mom1是Min/+小鼠肠道腺瘤大小和数量的半显性修饰基因。
Genetics. 1996 Dec;144(4):1769-76. doi: 10.1093/genetics/144.4.1769.
2
Low-molecular-weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and human.
Genomics. 1996 Mar 15;32(3):328-33. doi: 10.1006/geno.1996.0126.
3
Taking stock of complex trait genetics in mice.评估小鼠复杂性状遗传学。
Trends Genet. 1995 Dec;11(12):471-7. doi: 10.1016/s0168-9525(00)89155-6.
4
Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia.探索肠道肿瘤发生多步骤假说的转基因小鼠模型。
J Cell Biol. 1993 Nov;123(4):877-93. doi: 10.1083/jcb.123.4.877.
5
Germline p16 mutations in familial melanoma.家族性黑色素瘤中的种系p16突变
Nat Genet. 1994 Sep;8(1):15-21. doi: 10.1038/ng0994-15.
6
Bactericidal properties of murine intestinal phospholipase A2.
J Clin Invest. 1995 Feb;95(2):603-10. doi: 10.1172/JCI117704.
7
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Cell. 1995 Jun 16;81(6):957-66. doi: 10.1016/0092-8674(95)90015-2.
8
A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer.结节性硬化症（Tsc2）基因中的种系插入导致了显性遗传癌症的埃克大鼠模型。
Nat Genet. 1995 Jan;9(1):70-4. doi: 10.1038/ng0195-70.
9
Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.结节性硬化症2蛋白产物结节蛋白的鉴定。结节蛋白具有特定的Rap1GAP活性。
J Biol Chem. 1995 Jul 7;270(27):16409-14. doi: 10.1074/jbc.270.27.16409.
10
Suppression of intestinal neoplasia by DNA hypomethylation.DNA低甲基化对肠道肿瘤的抑制作用。
Cell. 1995 Apr 21;81(2):197-205. doi: 10.1016/0092-8674(95)90329-1.
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