Year: 2022

TRAIT-CENTRIC GENETICS. "As an aside, such observations imply that we need to be careful in not being too ‘trait-centric’ when considering the role of genes or gene variants in biological processes. Another example is that the most common cause of cystic fibrosis (a disease mainly of the lung) also causes male infertility." https://lnkd.in/dw8tEKD View in LinkedIn

RAMPANT POLYGENICITY. "The research community first had to come to grips with the rampant polygenicity of complex traits (despite a few remaining sceptics, the empirical evidence that quantitative traits and common disease are highly polygenic is overwhelming), so that it was natural to start with individual traits and then move to the study of multiple traits." https://lnkd.in/dw8tEKD View in LinkedIn

COMPLEX TRAIT POLYGENICITY. "Genome-wide association studies have identified many variants that each affects multiple traits, particularly across autoimmune diseases, cancers and neuropsychiatric disorders, suggesting that pleiotropic effects on human complex traits may be widespread." https://lnkd.in/duCFppG View in LinkedIn

PROBLEMS WITH STATISTICS. "The standard reductionist approach to biology, the prevalence of population‐based molecular assays, and the relative abundance of mean‐centric statistical tests have directed the vast majority of biological inquiry toward understanding the factors that influence phenotype means. Meanwhile, the dispersions of values around the mean and the shapes of the distributions have remained largely invisible or ignored." https://lnkd.in/dmHThkS View in LinkedIn

LIMITATIONS OF POPULATION MEANS. "Although the traditional approach of studying population means has proven fruitful in many situations, a growing body of evidence suggests that our understanding of many basic biological processes looks very different at the level of individuals and the phenomena that contribute to, or are contingent upon, differences between individuals have not received adequate attention." https://lnkd.in/dmHThkS View in LinkedIn

THREE SOURCES. "Phenotypic differences between individuals are derived from three sources: genetic variation, differences in environments, and stochastic processes." https://lnkd.in/dmHThkS View in LinkedIn

VARIANCE THINKING PARADIGM SHIFT. "Whereas genetic and environmental factors can have easily observable effects on phenotype mean values, the primary impact of stochastic events is on the variance associated with a given phenotype. Thinking about variances is still somewhat foreign to many biologists and requires new intellectual frameworks.” https://lnkd.in/dmHThkS View in LinkedIn

VARIATION AND DIFFERENTIATION. "It has long been appreciated that there is a need to limit fluctuations within a cell, but phenotypic heterogeneity can play a beneficial role. In order to produce tissues that comprise a mixture of cell types, many developmental processes have harnessed stochastic processes to facilitate differentiation." https://lnkd.in/dmHThkS View in LinkedIn

VISION EXAMPLE. "Color vision requires multiple types of photoreceptor cells that express different pigments. During development, chance interactions between enhancers and promoters can cause photoreceptor cells to express a single pigment gene. Heterogeneity in olfactory receptors seems to be established by similar mechanisms." https://lnkd.in/dmHThkS View in LinkedIn

MICROBIAL HETEROGENEITY. "Within microbial populations, epigenetic switching provides a constant source of phenotypic heterogeneity that can help a subset of cells to survive stressful conditions and take advantage of chance opportunities in an unpredictable environment." https://lnkd.in/dmHThkS View in LinkedIn