On the number of founding germ cells in humans.
Authors
Zheng-CJ; Luebeck-EG; Byers-B; Moolgavkar-SH
Source
Theor Biol Med Model 2005 Aug; 2:32
Abstract
Background: The number of founding germ cells (FGCs) in mammals is of fundamental significance to the fidelity of gene transmission between generations, but estimates from various methods vary widely. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women. Results: The germline-development model derives from the assumption that oogonial proliferation in the embryonic stage starts with a founding cells at t = 0 and that the subsequent proliferation can be defined as a simple stochastic birth process. It follows that the population size X(t) at the end of germline expansion (around the 5th month of pregnancy in humans; t = 0.42 years) is a random variable with a negative binomial distribution. A formula based on the expectation and variance of this random variable yields a moment-based estimate of a that is insensitive to the progressive reduction in oocyte numbers due to their utilization and apoptosis at later stages of life. In addition, we describe an algorithm for computing the maximum likelihood estimation of the FGC population size (a), as well as the rates of oogonial division and loss to apoptosis. Utilizing both of these approaches to evaluate available oocyte-counting data, we have obtained an estimate of a = 2 - 3 for Homo sapiens. Conclusion: The estimated number of founding germ cells in humans corresponds well with values previously derived from chimerical or mosaic mouse data. These findings suggest that the large variation in oocyte numbers between individual women is consistent with a smaller founding germ cell population size than has been estimated by cytological analyses.
Keywords
Biological-function; Biological-systems; Cell-biology; Cell-function; Cell-morphology; Cell-transformation; Cellular-function; Cellular-transport-mechanism; Cytology; Genes; Genetic-engineering; Genetic-factors; Genetics; Germ-cells; Mathematical-models; Statistical-analysis
Contact
Chang-Jiang Zheng, Department of Occupational and Environmental Medicine, Regions Hospital, University of Minnesota, 640 Jackson Street, Saint Paul, MN 55101
Document Type
Journal Article
Email Address
zhen0075@umn.edu
Identifying No.
Grant-Number-T42-OH-008434
Source Name
Theoretical Biology and Medical Modelling
Performing Organization
University of Minnesota Twin Cities
