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Analyzing observed or hidden heterogeneity on survival and mortality in an isogenic C. elegans cohort

View Article: PubMed Central - PubMed

ABSTRACT

It is generally difficult to understand the rates of human mortality from biological and biophysical standpoints because there are no cohorts or genetic homogeneity; in addition, information is limited regarding the various causes of death, such as the types of accidents and diseases. Despite such complexity, Gompertz’s rule is useful in humans. Thus, to characterize the rates of mortality from a demographic viewpoint, it would be interesting to research a single disease in one of the simplest organisms, the nematode C. elegans, which dies naturally under identically controlled circumstances without predators. Here, we report an example of the fact that heterogeneity on survival and mortality is observed through a single disease in a cohort of 100% genetically identical (isogenic) nematodes. Under the observed heterogeneity, we show that the diffusion theory, as a biophysical model, can precisely analyze the heterogeneity and conveniently estimate the degree of penetrance of a lifespan gene from the biodemographic data. In addition, we indicate that heterogeneity models are effective for the present heterogeneous data.

No MeSH data available.


Related in: MedlinePlus

Biodemographic data of the ife-2 mutant cohort. (A) Survival in a single trial, 97 animals at 25°C. This strain was transferred from 20°C to 25°C after L1 larvae. The fitting parameters of the 1st mode (blue curve) were l01 =30.9, t01 =7.0, and z1 =4.46, while those of the 2nd mode (red curve) were l02 =69.1, t02 =14.0, and z2 =3.49. (B) Mortality rates of (A). qx indicates the experimental values (open circles); qx′, the predicted mortality rates (filled circles); μx, the force of mortality (—). (C) Analysis by the Vaupel-Yashin model. The fitting parameters in Eq. 7 were chosen as π0 =0.15, A1 =0.00001, A2 =0.00110, G1 =1.20, and G2 =0.33.
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f3-5_59: Biodemographic data of the ife-2 mutant cohort. (A) Survival in a single trial, 97 animals at 25°C. This strain was transferred from 20°C to 25°C after L1 larvae. The fitting parameters of the 1st mode (blue curve) were l01 =30.9, t01 =7.0, and z1 =4.46, while those of the 2nd mode (red curve) were l02 =69.1, t02 =14.0, and z2 =3.49. (B) Mortality rates of (A). qx indicates the experimental values (open circles); qx′, the predicted mortality rates (filled circles); μx, the force of mortality (—). (C) Analysis by the Vaupel-Yashin model. The fitting parameters in Eq. 7 were chosen as π0 =0.15, A1 =0.00001, A2 =0.00110, G1 =1.20, and G2 =0.33.

Mentions: As shown in Fig. 3, similar data to those of egl-1 mutants were obtained with another mutant of the ife-2 gene. Differently from the case of the egl-1 mutant, however, in this mutant, the reason for the two phases is unclear; in other words, it is a case of hidden heterogeneity, probably due to the low penetrance of the ife-2 gene. The frequency of the first mode from our model was estimated to be 0.309.


Analyzing observed or hidden heterogeneity on survival and mortality in an isogenic C. elegans cohort
Biodemographic data of the ife-2 mutant cohort. (A) Survival in a single trial, 97 animals at 25°C. This strain was transferred from 20°C to 25°C after L1 larvae. The fitting parameters of the 1st mode (blue curve) were l01 =30.9, t01 =7.0, and z1 =4.46, while those of the 2nd mode (red curve) were l02 =69.1, t02 =14.0, and z2 =3.49. (B) Mortality rates of (A). qx indicates the experimental values (open circles); qx′, the predicted mortality rates (filled circles); μx, the force of mortality (—). (C) Analysis by the Vaupel-Yashin model. The fitting parameters in Eq. 7 were chosen as π0 =0.15, A1 =0.00001, A2 =0.00110, G1 =1.20, and G2 =0.33.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036638&req=5

f3-5_59: Biodemographic data of the ife-2 mutant cohort. (A) Survival in a single trial, 97 animals at 25°C. This strain was transferred from 20°C to 25°C after L1 larvae. The fitting parameters of the 1st mode (blue curve) were l01 =30.9, t01 =7.0, and z1 =4.46, while those of the 2nd mode (red curve) were l02 =69.1, t02 =14.0, and z2 =3.49. (B) Mortality rates of (A). qx indicates the experimental values (open circles); qx′, the predicted mortality rates (filled circles); μx, the force of mortality (—). (C) Analysis by the Vaupel-Yashin model. The fitting parameters in Eq. 7 were chosen as π0 =0.15, A1 =0.00001, A2 =0.00110, G1 =1.20, and G2 =0.33.
Mentions: As shown in Fig. 3, similar data to those of egl-1 mutants were obtained with another mutant of the ife-2 gene. Differently from the case of the egl-1 mutant, however, in this mutant, the reason for the two phases is unclear; in other words, it is a case of hidden heterogeneity, probably due to the low penetrance of the ife-2 gene. The frequency of the first mode from our model was estimated to be 0.309.

View Article: PubMed Central - PubMed

ABSTRACT

It is generally difficult to understand the rates of human mortality from biological and biophysical standpoints because there are no cohorts or genetic homogeneity; in addition, information is limited regarding the various causes of death, such as the types of accidents and diseases. Despite such complexity, Gompertz’s rule is useful in humans. Thus, to characterize the rates of mortality from a demographic viewpoint, it would be interesting to research a single disease in one of the simplest organisms, the nematode C. elegans, which dies naturally under identically controlled circumstances without predators. Here, we report an example of the fact that heterogeneity on survival and mortality is observed through a single disease in a cohort of 100% genetically identical (isogenic) nematodes. Under the observed heterogeneity, we show that the diffusion theory, as a biophysical model, can precisely analyze the heterogeneity and conveniently estimate the degree of penetrance of a lifespan gene from the biodemographic data. In addition, we indicate that heterogeneity models are effective for the present heterogeneous data.

No MeSH data available.


Related in: MedlinePlus