Murine chromosomal regions correlated with longevity.
Murine chromosomal regions correlated with longevity.
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DOI：
10.1093/genetics/118.4.693
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发表时间：
1988-04
期刊：
影响因子：
3.3
通讯作者：
Rebecca Gelman;Ada Watson;Roderick Bronson;Edmond J. Yunis
中科院分区：
文献类型：
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作者：
Rebecca Gelman;Ada Watson;Roderick Bronson;Edmond J. Yunis
在对360只BXD重组近交系雌性小鼠（20个不同品系）进行的寿命分析中，2个品系的生存期非常显著地短于其他17个品系，1个品系的生存期非常显著地长于其他17个品系;在生存的比例风险模型中，与其他13个品系相比，其他4个品系的生存期延长不太显著。最短寿命菌株的平均存活期为479天;最长寿命菌株的平均存活期几乎是其两倍（904天）。应变内的生存范围是非常大的（平均642天），应变占生存的变化只有29%，表明有重要的环境和/或特殊的发展影响寿命，即使在这个殖民地住在一个房间。每个菌株已分型的15条染色体上的141个区域的标记，这些标记中的101个具有可区分的分布在20株。两个寿命最短的菌株有63%的标记具有相同的等位基因。与存活率最显著相关的单个区域（由7号染色体上的P450、Coh、Xmmv-35标记）将小鼠分成两组，存活中值相差153天（B基因型小鼠为755天; D基因型小鼠为602天）。单独评估，发现44%的遗传标记（包括15条染色体中的11条上的一些标记，其中任何标记都是分型的）与存活率显著相关（P小于0.05），尽管人们仅期望5%的标记偶然具有显著性。虽然许多标志物的研究应该调整多重比较问题，这些粗P值的一种解释是，任何实验只有一个这些“显着”标志物类型将可能得出结论，标志物是一个显着的预测生存。两种类型的多元回归模型被用来检查与基因组的生存的相关性。当根据基因型区域进行生存比例风险模型时，六个遗传区域模型与生存最相关：在7号染色体上以P450、Coh、Xmmv-35为标记（B等位基因寿命更长），2号染色体上的Ly-24（B等位基因寿命更长）、2号染色体上的β 2 M和H-3（D等位基因寿命更长）1号染色体上的Lamb-2（D等位基因寿命更长），1号染色体上的Ltw-4（B等位基因寿命更长）和12号染色体的Igh区域（Igh-Sa 4、Igh-Sa 2、Igh-Bgl、Igh-Nbp、Igh-Npid、Igh-Gte、Odc-8和Ox-1; D等位基因寿命更长）。（400字处截断摘要）
In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room. Each strain had been typed for markers of 141 regions on 15 chromosomes; 101 of these markers had distinguishable distributions on the 20 strains. The two shortest lived strains had the same alleles for 63% of the markers. The single region most significantly correlated with survival (marked by P450, Coh, Xmmv-35 on chromosome 7) divided the mice into two groups with survival medians which differed by 153 days (755 days for mice with a B genotype; 602 days for mice with a D genotype). Evaluated individually, 44% of the genetic markers (including some markers on 11 of 15 chromosomes with any markers typed) were found to be significantly correlated with survival (P less than 0.05) although one would only expect 5% of the markers to be significant by chance. While studies of many markers should adjust for the multiple comparisons problem, one interpretation of these crude P values is that any experiment with only one of these "significant" markers typed would be likely to conclude that the marker was a significant predictor of survival. Two types of multiple regression models were used to examine the correlation with survival of groups of genes. When a proportional hazards model for survival was done in terms of genotype regions, a six genetic region model best correlated with survival: that marked by P450, Coh, Xmmv-35 on chromosome 7 (B allele lives longer), Ly-24 on chromosome 2 (B allele lives longer), beta 2M and H-3 on chromosome 2 (D allele lives longer) Lamb-2 on chromosome 1 (D allele lives longer), Ltw-4 on chromosome 1 (B allele lives longer), and the Igh area of chromosome 12 (Igh-Sa4, Igh-Sa2, Igh-Bgl, Igh-Nbp, Igh-Npid, Igh-Gte, Odc-8, and Ox-1; D allele lives longer).(ABSTRACT TRUNCATED AT 400 WORDS)