An Introduction to Quantitative Genetics I Heather a Lawson Advanced Genetics Spring2018 Outline
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Biology Incomplete Dominance 5E Model Lesson
BIOLOGY INCOMPLETE DOMINANCE 5E MODEL LESSON Teacher: Expected Length of Lesson Topic: Unit: Heather Lesson: Incomplete Genetics Yarbrough 1 - 90 minute class Dominance SB3. Obtain, evaluate, and communicate information to analyze how biological traits are passed on to successive generations. Targeted Content Standards/ b. Use mathematical models to predict and explain patterns of inheritance. Element: (Clarification statement: Students should be able to use Punnett squares (Include the entire standard) (monohybrid and dihybrid crosses) and/or rules of probability, to analyze the following inheritance patterns: dominance, codominance, incomplete dominance.) L9-10RST2: Determine the central ideas or conclusions of a text; trace the text’s explanation or depiction of a complex process, phenomenon, or concept; provide an accurate summary of the text. L9-10RST7: Translate quantitative or technical information expressed in words in a text into visual form (e.g., a table or chart) and translate information expressed visually or mathematically (e.g., in an equation) into words. L9-10RST9: Compare and contrast findings presented in a text to those Targeted Literacy Skills or Standards: (include as many as your from other sources (including their own experiments), noting when the lesson incorporates) findings support or contradict previous explanations or accounts. L9-10WHST2: Write informative/explanatory texts, including the narration of historical events, scientific procedures/ experiments, or technical processes. d. Use precise language and domain-specific vocabulary to manage the complexity of the topic and convey a style appropriate to the discipline and context as well as to the expertise of likely readers. L9-10WHST4: Produce clear and coherent writing in which the development, organization, and style are appropriate to task, purpose, and audience. -
A Comprehensive Study of Metabolite Genetics Reveals Strong Pleiotropy and Heterogeneity Across Time and Context
ARTICLE https://doi.org/10.1038/s41467-019-12703-7 OPEN A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context Apolline Gallois1,12, Joel Mefford2,12, Arthur Ko 3, Amaury Vaysse 1, Hanna Julienne1, Mika Ala-Korpela4,5,6,7,8,9, Markku Laakso 10, Noah Zaitlen2,12*, Päivi Pajukanta 3,12*& Hugues Aschard 1,11,12* 1234567890():,; Genetic studies of metabolites have identified thousands of variants, many of which are associated with downstream metabolic and obesogenic disorders. However, these studies have relied on univariate analyses, reducing power and limiting context-specific under- standing. Here we aim to provide an integrated perspective of the genetic basis of meta- bolites by leveraging the Finnish Metabolic Syndrome In Men (METSIM) cohort, a unique genetic resource which contains metabolic measurements, mostly lipids, across distinct time points as well as information on statin usage. We increase effective sample size by an average of two-fold by applying the Covariates for Multi-phenotype Studies (CMS) approach, identifying 588 significant SNP-metabolite associations, including 228 new associations. Our analysis pinpoints a small number of master metabolic regulator genes, balancing the relative proportion of dozens of metabolite levels. We further identify associations to changes in metabolic levels across time as well as genetic interactions with statin at both the master metabolic regulator and genome-wide level. 1 Department of Computational Biology - USR 3756 CNRS, Institut Pasteur, Paris, France. 2 Department of Medicine, University of California, San Francisco, CA, USA. 3 Department of Human Genetics, University of California, Los Angeles, CA, USA. -
Heritability in the Era of Molecular Genetics: Some Thoughts for Understanding Genetic Influences on Behavioural Traits
European Journal of Personality, Eur. J. Pers. 25: 254–266 (2011) Published online (wileyonlinelibrary.com) DOI: 10.1002/per.836 Heritability in the Era of Molecular Genetics: Some Thoughts for Understanding Genetic Influences on Behavioural Traits WENDY JOHNSON1,2*, LARS PENKE1 and FRANK M. SPINATH3 1Centre for Cognitive Ageing and Cognitive Epidemiology and Department of Psychology, University of Edinburgh, Edinburgh, UK 2Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA 3Department of Psychology, Saarland University, Saarbruecken, Germany Abstract: Genetic influences on behavioural traits are ubiquitous. When behaviourism was the dominant paradigm in psychology, demonstrations of heritability of behavioural and psychological constructs provided important evidence of its limitations. Now that genetic influences on behavioural traits are generally accepted, we need to recognise the limitations of heritability as an indicator of both the aetiology and likelihood of discovering molecular genetic associations with behavioural traits. We review those limitations and conclude that quantitative genetics and genetically informative research designs are still critical to understanding the roles of gene‐environment interplay in developmental processes, though not necessarily in the ways commonly discussed. Copyright © 2011 John Wiley & Sons, Ltd. Key words: genetic influences; twin study; heritability Much is often made of new findings of the presence of environmental influences but emphasised that these genetic influences -
Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B
Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B. M ü ller, G ü nter P. Wagner, and Werner Callebaut, editors The Evolution of Cognition , edited by Cecilia Heyes and Ludwig Huber, 2000 Origination of Organismal Form: Beyond the Gene in Development and Evolutionary Biology , edited by Gerd B. M ü ller and Stuart A. Newman, 2003 Environment, Development, and Evolution: Toward a Synthesis , edited by Brian K. Hall, Roy D. Pearson, and Gerd B. M ü ller, 2004 Evolution of Communication Systems: A Comparative Approach , edited by D. Kimbrough Oller and Ulrike Griebel, 2004 Modularity: Understanding the Development and Evolution of Natural Complex Systems , edited by Werner Callebaut and Diego Rasskin-Gutman, 2005 Compositional Evolution: The Impact of Sex, Symbiosis, and Modularity on the Gradualist Framework of Evolution , by Richard A. Watson, 2006 Biological Emergences: Evolution by Natural Experiment , by Robert G. B. Reid, 2007 Modeling Biology: Structure, Behaviors, Evolution , edited by Manfred D. Laubichler and Gerd B. M ü ller, 2007 Evolution of Communicative Flexibility: Complexity, Creativity, and Adaptability in Human and Animal Communication , edited by Kimbrough D. Oller and Ulrike Griebel, 2008 Functions in Biological and Artifi cial Worlds: Comparative Philosophical Perspectives , edited by Ulrich Krohs and Peter Kroes, 2009 Cognitive Biology: Evolutionary and Developmental Perspectives on Mind, Brain, and Behavior , edited by Luca Tommasi, Mary A. Peterson, and Lynn Nadel, 2009 Innovation in Cultural Systems: Contributions from Evolutionary Anthropology , edited by Michael J. O ’ Brien and Stephen J. Shennan, 2010 The Major Transitions in Evolution Revisited , edited by Brett Calcott and Kim Sterelny, 2011 Transformations of Lamarckism: From Subtle Fluids to Molecular Biology , edited by Snait B. -
Evolution by Natural Selection, Formulated Independently by Charles Darwin and Alfred Russel Wallace
UNIT 4 EVOLUTIONARY PATT EVOLUTIONARY E RNS AND PROC E SS E Evolution by Natural S 22 Selection Natural selection In this chapter you will learn that explains how Evolution is one of the most populations become important ideas in modern biology well suited to their environments over time. The shape and by reviewing by asking by applying coloration of leafy sea The rise of What is the evidence for evolution? Evolution in action: dragons (a fish closely evolutionary thought two case studies related to seahorses) 22.1 22.4 are heritable traits that with regard to help them to hide from predators. The pattern of evolution: The process of species have changed evolution by natural and are related 22.2 selection 22.3 keeping in mind Common myths about natural selection and adaptation 22.5 his chapter is about one of the great ideas in science: the theory of evolution by natural selection, formulated independently by Charles Darwin and Alfred Russel Wallace. The theory explains how T populations—individuals of the same species that live in the same area at the same time—have come to be adapted to environments ranging from arctic tundra to tropical wet forest. It revealed one of the five key attributes of life: Populations of organisms evolve. In other words, the heritable characteris- This chapter is part of the tics of populations change over time (Chapter 1). Big Picture. See how on Evolution by natural selection is one of the best supported and most important theories in the history pages 516–517. of scientific research. -
High Heritability of Telomere Length, but Low Evolvability, and No Significant
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.16.423128; this version posted December 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 High heritability of telomere length, but low evolvability, and no significant 2 heritability of telomere shortening in wild jackdaws 3 4 Christina Bauch1*, Jelle J. Boonekamp1,2, Peter Korsten3, Ellis Mulder1, Simon Verhulst1 5 6 Affiliations: 7 1 Groningen Institute for Evolutionary Life Sciences, University of Groningen, Nijenborgh 7, 8 9747AG Groningen, The Netherlands 9 2 present address: Institute of Biodiversity Animal Health & Comparative Medicine, College 10 of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United 11 Kingdom 12 3 Department of Animal Behaviour, Bielefeld University, Morgenbreede 45, 33615 Bielefeld, 13 Germany 14 15 16 * Correspondence to: 17 [email protected] 18 19 Running head: High heritability of telomere length bioRxiv preprint doi: https://doi.org/10.1101/2020.12.16.423128; this version posted December 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 20 Abstract 21 Telomere length (TL) and shortening rate predict survival in many organisms. Evolutionary 22 dynamics of TL in response to survival selection depend on the presence of genetic variation 23 that selection can act upon. However, the amount of standing genetic variation is poorly known 24 for both TL and TL shortening rate, and has not been studied for both traits in combination in 25 a wild vertebrate. -
Special Issues on Advances in Quantitative Genetics: Introduction
Heredity (2014) 112, 1–3 & 2014 Macmillan Publishers Limited All rights reserved 0018-067X/14 www.nature.com/hdy EDITORIAL Special issues on advances in quantitative genetics: introduction Heredity (2014) 112, 1–3; doi:10.1038/hdy.2013.115 Fisher’s (1918) classic paper on the inheritance of complex traits not While much of the focus was on standard biometrical applications only founded the field of quantitative genetics, but also coined the (for example, variance components), hints of things to come were term variance and introduced the powerful statistical method of foreshadowed by papers on the relevance of molecular biology to analysis of variance. This was a watershed paper, reconciling the breeding and applications of mixed models (models including both Mendelian’s discrete and saltatorial view of trait evolution with the fixed and random effects, for example, BLUP and REML). Much of gradual and continuous view of Darwin’s followers, the biometricians the emphasis was on breeding or laboratory populations. A decade (Provine, 1971). This fusion of Mendelian genetics with Darwinian later, the second ICQG held at Raleigh, North Carolina in 1987 natural selection was the start of the modern evolutionary synthesis. (Weir et al., 1988), reflected explosive growth in new tools (low- Fisher’s paper also marked a critical point in modern statistics, and density molecular markers for early quantitative trait locus (QTL) this synergism between the development of new statistical methods mapping), a continued expansion of the importance of mixed-model and the ever-increasing complexity of genetic/genomic data sets methodology for complex estimation issues, and a growing fusion of continues to this day. -
Genetics in Harry Potter's World: Lesson 2
Genetics in Harry Potter’s World Lesson 2 • Beyond Mendelian Inheritance • Genetics of Magical Ability 1 Rules of Inheritance • Some traits follow the simple rules of Mendelian inheritance of dominant and recessive genes. • Complex traits follow different patterns of inheritance that may involve multiples genes and other factors. For example, – Incomplete or blended dominance – Codominance – Multiple alleles – Regulatory genes Any guesses on what these terms may mean? 2 Incomplete Dominance • Incomplete dominance results in a phenotype that is a blend of a heterozygous allele pair. Ex., Red flower + Blue flower => Purple flower • If the dragons in Harry Potter have fire-power alleles F (strong fire) and F’ (no fire) that follow incomplete dominance, what are the phenotypes for the following dragon-fire genotypes? – FF – FF’ – F’F’ 3 Incomplete Dominance • Incomplete dominance results in a phenotype that is a blend of the two traits in an allele pair. Ex., Red flower + Blue flower => Purple flower • If the Dragons in Harry Potter have fire-power alleles F (strong fire) and F’ (no fire) that follow incomplete dominance, what are the phenotypes for the following dragon-fire genotypes: Genotypes Phenotypes FF strong fire FF’ moderate fire (blended trait) F’F’ no fire 4 Codominance • Codominance results in a phenotype that shows both traits of an allele pair. Ex., Red flower + White flower => Red & White spotted flower • If merpeople have tail color alleles B (blue) and G (green) that follow the codominance inheritance rule, what are possible genotypes and phenotypes? Genotypes Phenotypes 5 Codominance • Codominance results in a phenotype that shows both traits of an allele pair. -
Roadmap • Optimal Mutation Rate • Dominance and Its Implications
Roadmap • Optimal mutation rate • Dominance and its implications { Why is an allele dominant or recessive? { Overdominance (heterozygote advantage) { Underdominance (heterozygote inferiority) One minute responses • Q: I don't understand degrees of freedom! (About six of these....) • Q: Show the calculation of µ and ν Degrees of freedom revisited Thanks to Patrick Runkel: http://blog.minitab.com/blog/statistics-and-quality-data-analysis/ what-are-degrees-of-freedom-in-statistics A a Total A 20 a 10 Total 15 15 One more look at degrees of freedom Fictional data for sickle-cell hemoglobin (alleles A and S) in African-American adults Normal AA 400 Carrier AS 90 Affected SS 10 • Suppose I told you: { How many people I sampled { How many of each allele I found { How many AS carriers I found • Are there any possible surprises left in the data? (AA? SS?) • This is why there is only 1 df Mu and nu • µ (mu, forward mutation rate) { mutation rate per site is observed { rate per significant site in gene is: { rate per site x number of significant sites • ν (nu, back mutation rate) { mutation rate per site is observed { need the right nucleotide (1/3 chance) { rate per site x 1/3 Is mutation good or bad? • Most mutations have no fitness effect • Of those that do, most are bad • Most organisms expend significant energy trying to avoid mutations (DNA proofreading, etc) • Are organisms trying (and failing) to reach a mutation rate of zero? • Could there be selection in favor of a non-zero rate? Transposons as mutagens • Transposons are genetic elements that -
Environment-Sensitive Epigenetics and the Heritability of Complex Diseases
INVESTIGATION Environment-Sensitive Epigenetics and the Heritability of Complex Diseases Robert E. Furrow,*,1 Freddy B. Christiansen,† and Marcus W. Feldman* *Department of Biology, Stanford University, Stanford, California 94305, and †Department of Bioscience and Bioinformatics Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark ABSTRACT Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the “missing heritability” problem. However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases. We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation. We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance. These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance and similar to those expected from genetic effects. The results suggest that epigenetic variation, inherited both directly and through shared environmental effects, may make a key contribution to the missing heritability. HE challenges of identifying the common or rare genes a change in DNA sequence. Such modifications include Tthat contribute to the transmission of heritable human methylation of cytosine nucleotides at CpG sites and histone diseases and other complex phenotypes have been discussed protein modification. Such epigenetic modifications may be for some time (Moran 1973; Layzer 1974; Feldman and transmissible across generations or arise de novo each gen- Lewontin 1975; Kamin and Goldberger 2002). -
New Strategies and Tools in Quantitative Genetics: How to Go from the Phenotype to the Genotype
PP68CH16-Loudet ARI 6 April 2017 9:43 ANNUAL REVIEWS Further Click here to view this article's online features: • Download figures as PPT slides • Navigate linked references • Download citations New Strategies and Tools in • Explore related articles • Search keywords Quantitative Genetics: How to Go from the Phenotype to the Genotype Christos Bazakos, Mathieu Hanemian, Charlotte Trontin, JoseM.Jim´ enez-G´ omez,´ and Olivier Loudet Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Universite´ Paris-Saclay, 78026 Versailles Cedex, France; email: [email protected] Annu. Rev. Plant Biol. 2017. 68:435–55 Keywords First published online as a Review in Advance on genetic architecture, QTL, RIL, GWAS, phenotype February 6, 2017 The Annual Review of Plant Biology is online at Abstract plant.annualreviews.org Quantitative genetics has a long history in plants: It has been used to study https://doi.org/10.1146/annurev-arplant-042916- specific biological processes, identify the factors important for trait evolu- 040820 Annu. Rev. Plant Biol. 2017.68:435-455. Downloaded from www.annualreviews.org tion, and breed new crop varieties. These classical approaches to quantitative Copyright c 2017 by Annual Reviews. trait locus mapping have naturally improved with technology. In this review, All rights reserved we show how quantitative genetics has evolved recently in plants and how new developments in phenotyping, population generation, sequencing, gene Access provided by INRA Institut National de la Recherche Agronomique on 05/05/17. For personal use only. manipulation, and statistics are rejuvenating both the classical linkage map- ping approaches (for example, through nested association mapping) as well as the more recently developed genome-wide association studies. -
Investigations Into Roles for Endocytosis in LIN-12/Notch
Investigations into roles for endocytosis in LIN-12/Notch signaling and its regulation Jessica Chan Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2020 © 2020 Jessica Chan All Rights Reserved Abstract The LIN-12/Notch signaling pathway is highly conserved in all animals, and is crucial for proper development. It is a key pathway in specifying cell fate in many cellular contexts, and dysregulation of the pathway can have deleterious consequences. Therefore, understanding how LIN-12/Notch signaling is regulated in different contexts has been a main area of interest in the field. Previous studies in different model organisms have identified many modes of regulation of the signaling pathway, one of which is endocytosis of the ligand and receptor. Here, I further investigated the role of endocytosis in LIN-12/Notch signaling in multiple developmental contexts in Caenorhabditis elegans. Work in Drosophila and vertebrates had previously established that ligand-mediated activation of Notch requires ubiquitination of the intracellular domain of the transmembrane ligand and the activity of the endocytic adaptor Epsin in the signaling cell. The consensus in the field is that Epsin-mediated endocytosis of mono-ubiquitinated ligand generates a pulling force that exposes a cleavage site in Notch for an ADAM protease, a critical step in signal transduction. In contrast, in this thesis, I examined two different transmembrane ligands in several different cell contexts and found that activation of LIN-12/Notch and the paralogous GLP-1/Notch in C.