@article{21841,
  abstract     = {The long-standing notion that genotypes map to phenotypes through simple one gene–one trait relationships continues to shape both research in the life sciences and public understanding, with implications for policy and funding priorities. Yet this paradigm is increasingly recognized as inadequate for explaining continuous phenotypic variation and the complex genetic architectures of the genotype–phenotype map. Modern genetics emerged from the early 20th-century synthesis of Mendelian and biometric schools of heredity, with R.A. Fisher demonstrating early on how multiple discrete loci could collectively produce continuous variation. Despite this fundamental insight, Mendelism—with its focus on single genes and standardized genetic backgrounds—became the dominant framework, shaping current genetics research and molecular biology as well as science education. The advent of large-scale genomic data has revealed yet again the limitations of this reductionist approach. Evidence from quantitative genetics now shows that most phenotypes arise from complex networks of many interdependent genes and their dynamic responses to environmental perturbations. Here we trace the historical roots of how Mendelian classical genetics departed from the biometric school to create the current predominant paradigm in genetics, despite fundamentally unresolved issues. Moving on from this one-sided paradigm will require systematic development of integrative, evolutionarily grounded experimental approaches that better capture the multigenic and context-dependent nature of inheritance. Achieving such an extended perspective will require methodological innovation, including advances in large-scale (e.g. automated) phenotyping. Dedicated research programs will be necessary to advance a new era of genetic research into the complex mechanisms underlying phenotypic variation.},
  author       = {Tautz, Diethard and Pallares, Luisa F and Andersson, Leif and Barghi, Neda and Barton, Nicholas H and Bay, Rachael and Chan, Yingguang Frank and Hancock, Angela and Kaiser, Tobias S and Koenig, Daniel and Kontarakis, Zacharias and Liedvogel, Miriam and de Meaux, Juliette and Nordborg, Magnus and Palmer, Abraham A and Purugganan, Michael and Schlötterer, Christian and Schmid, Karl and Stainier, Didier Y R and Weigel, Detlef and Wolf, Jochen B W and Ebert, Dieter and Gibson, Greg},
  issn         = {1943-2631},
  journal      = {Genetics},
  keywords     = {classic genetics, quantitative genetics, genotype–phenotype map},
  number       = {4},
  publisher    = {Oxford University Press},
  title        = {{Beyond Mendel: A call to revisit the genotype–phenotype map through new experimental paradigms}},
  doi          = {10.1093/genetics/iyag024},
  volume       = {232},
  year         = {2026},
}

@misc{12949,
  abstract     = {The classical infinitesimal model is a simple and robust model for the inheritance of quantitative traits. In this model, a quantitative trait is expressed as the sum of a genetic and a non-genetic (environmental) component and the genetic component of offspring traits within a family follows a normal distribution around the average of the parents’ trait values, and has a variance that is independent of the trait values of the parents. Although the trait distribution across the whole population can be far from normal, the trait distributions within families are normally distributed with a variance-covariance matrix that is determined entirely by that in  the ancestral population and the probabilities of identity determined by the pedigree. Moreover, conditioning on some of the trait values within the pedigree has predictable effects on the mean and variance within and between families. In previous work, Barton et al. (2017), we showed that when trait values are determined by the sum of a large number of Mendelian factors, each  of small effect, one can justify the infinitesimal model as limit of Mendelian inheritance. It was also shown that under some forms of epistasis, trait values within a family are still normally distributed.},
  author       = {Barton, Nicholas H},
  keywords     = {Quantitative genetics, infinitesimal model},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{The infinitesimal model with dominance}},
  doi          = {10.15479/AT:ISTA:12949},
  year         = {2023},
}