控制对γ射线诱导的胸腺淋巴瘤易感性的基因位点。

Genetic loci controlling susceptibility to gamma-ray-induced thymic lymphoma.

作者信息

Saito Y, Ochiai Y, Kodama Y, Tamura Y, Togashi T, Kosugi-Okano H, Miyazawa T, Wakabayashi Y, Hatakeyama K, Wakana S, Niwa O, Kominami R

机构信息

First Department of Biochemistry, Niigata University School of Medicine, Asahimachi 1-757, Niigata 951-8122, Japan.

出版信息

Oncogene. 2001 Aug 23;20(37):5243-7. doi: 10.1038/sj.onc.1204675.

DOI:10.1038/sj.onc.1204675

PMID:11526516

Abstract

BALB/c is a susceptible strain for the development of gamma-ray induced mouse thymic lymphoma whereas MSM shows resistance. Association analysis of 220 backcross mice between the two strains using 67 markers was carried out to identify loci involved in the control of susceptibility. The genotype of mice with lymphoma showed excess heterozygosity relative to MSM homozygosity at D2Mit15 and D4Mit12 and was skewed toward MSM-derived alleles at D5Mit5. The P values in Mantel-Cox test were 0.0048 (D2Mit15), 0.0034 (D4Mit12) and 0.0048 (D5Mit5), suggesting association at the three loci in the susceptibility. Cooperative effect on lymphomagenesis was also observed among the three loci. To obtain independent evidence for linkage at D4Mit12, we made partially congenic mice in which a D4Mit12 region in BALB/c was replaced by MSM-derived homolog. Examination for the lymphoma susceptibility in 78 progeny of the congenic mice confirmed the effect of the locus near D4Mit12 (P=0.0037). The result, together with the linkage analysis, shows that the locus near D4Mit12 is regarded as a confirmed linkage but the other two loci as marginally suggestive.

摘要

BALB/c是对γ射线诱导的小鼠胸腺淋巴瘤发展敏感的品系，而MSM表现出抗性。使用67个标记对两个品系之间的220只回交小鼠进行关联分析，以确定参与易感性控制的基因座。患有淋巴瘤的小鼠的基因型在D2Mit15和D4Mit12处相对于MSM纯合子显示出过量的杂合性，并且在D5Mit5处偏向于MSM衍生的等位基因。Mantel-Cox检验中的P值分别为0.0048（D2Mit15）、0.0034（D4Mit12）和0.0048（D5Mit5），表明这三个基因座与易感性相关。在这三个基因座之间也观察到对淋巴瘤发生的协同作用。为了获得D4Mit12处连锁的独立证据，我们制作了部分同源基因小鼠，其中BALB/c中的D4Mit12区域被MSM衍生的同源物取代。对78只同源基因小鼠后代的淋巴瘤易感性检查证实了D4Mit12附近基因座的作用（P=0.0037）。该结果与连锁分析一起表明，D4Mit12附近的基因座被视为已确认的连锁，但其他两个基因座仅具有微弱的提示性。