New experimental support for long standing concepts of polygenic genetics implies that the Mendelian genetic paradigm needs to be revised

The New (Old) Genetics, Version 1.0

Abstract

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The field of Genetics started flourishing after the rediscovery of the Mendelian laws of inheritance at the beginning of the 20th century. These laws are based on a discrete classification of phenotypes and their causative genes. Such a Mendelian way of thinking forms the foundation of modern molecular biology, with its experimental paradigm that a gene function is inferred from the knock-out of the gene. However, most phenotypes are not discrete. Human height, for example, is a continuous phenotype and height measures approximate a Gaussian distribution. The statistical foundation for the genetics of human height was worked out by GALTON at the end of the 19th century. He established the basis of quantitative genetics, a field that has driven the agricultural and breeding programs in the past century. It is not until very recently that the technical developments behind the human genome project have paved the way to reconcile the two contrasting ways of genetic thinking – Mendelian genetics and statistical genetics – through genome-wide analyses. It has now become clear that most phenotypes are rarely determined by single Mendelian genes, but instead, many genes contribute to their determination and variation. It has even been suggested in the omnigenic model that all genes that are expressed at the appropriate time contribute to any given phenotype. These insights are stimulating a major rethinking of how the linear genetic information laid down in the deoxyribonucleic acid (DNA) is converted into the threedimensional structure of an individual. The new conceptual and experimental paradigms have already revolutionized animal and plant breeding. In the field of human genetics, the realization that common diseases also have a polygenic basis is raising new challenges for treatment. And finally, in basic sciences like molecular and evolutionary biology, researchers are starting to revisit traditional, but oversimplified concepts on how genes act and how evolutionary adaptation works.

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