Quantitative GeneticsA loose distinctionGene for starting businessesSlide 4Gene for metaphorsThe God Gene“Nature vs. nurture”: the curse of “folk wisdom”In a population, phenotypes of individuals for a quantitative trait tend to be normally distributedCentral limit theorem Carl Friedrich Gauss Slide 10Slide 11Is trait X heritable?PellagraSlide 14Mapping of quantitative trait loci (QTLs)Slide 16QTL mapping, version 1“Mood disorders”: anxiety“Serotonin transporter genetic variation and the response of the human amygdala”Slide 20Slide 21Living With Our Genes D. Hamer and P. Copeland (1998)QTL mapping, version 2Mapping a qualitative trait by linkageSlide 25Slide 26Slide 27Slide 28Well-saidProblemSighA pernicious line of reasoningMisunderstanding a fundamental distinction between quantitative and qualitative traitsNorm of reactionSlide 35Slide 36Slide 37Risk of breast cancer and physical exercise in BRCA1/2 mutation carriers: an example of how the norm of reaction illuminates the modification of a “genetic tendency” by environmentSlide 39Nature vs. Nurture: Wrong Question!And therefore …Genetics of “intelligence”“The Bell Curve” (1994) R.J. Herrnstein and C. MurrayPublic vs. private dialogueCalling a spade a spadeFor the recordWhat do the data show?Point 1 – the reification of IQSlide 49SpeedPoint 2 – the heritability of the “trait” that IQ tests measureEnvironmental vs. genetic variance in quantitative traitsSlide 53Slide 54Two sources of varianceSlide 56… and thereforeWhat H2 does NOT meanSlide 59Narrow-sense heritability, h2A closer look at genetic varianceSlide 62Components of varianceThe useful part of genetic varianceA definition of narrow-sense heritabilityFact and problemEstimates of narrow-sense heritability from regression of offspring on parentsRegression of y on xSlide 69Gasp! Regression of offspring on midparents yields a line the slope of which is the elusive narrow-sense heritability!!!Resemblance between relatives (a simplification)Slide 72Slide 73The importance of the wombNature, July ’97: “The heritability of IQ”Slide 76Hmmmm….Dysgenesis, huh?A perspective on the allure of the “dream of blue blood”Further reading on this subject1MCB 140, 12-8-06Quantitative Genetics2MCB 140, 12-8-06A loose distinction“Qualitative” traits:• Blood groups (ABO)• Coat color in cats• Color visionDifference between phenotypes of two individuals can be explained by difference in genotype at a small number of loci (for example, 1 or 2).Mendelian ratios in F1Quantitative traits:• Height• Weight• Facial featuresThe phenotype is determined – to some extent – by genotype, but phenotypic difference between individuals is due to difference in genotype at a large number of loci.No Mendelian ratios in F13MCB 140, 12-8-06Gene for starting businesses“If you belong to a certain extended family in Seattle, you're probably an entrepreneur. It seems to be about the only career many of the members ever considered. ''It's in our blood'' said Brian Jacobsen, president of Madison Park Greetings, a stationery and gifts company. Mr. Jacobsen's brother, mother, grandfather, two uncles, two cousins and an aunt all started and ran their own companies and say they cannot imagine any other livelihood. Why are so many people in the same clan hooked? Some of them have a theory. They believe that somewhere in their chromosomes lurks an actual entrepreneurial gene -- that their bent for business really is in their blood.”New York Times, Nov. 20, 2003 – p. C84MCB 140, 12-8-06New York Times, Nov. 20, 2003 – p. C85MCB 140, 12-8-06Gene for metaphors“AG: Many of your songs include clear, visual images. Do these images come from dreams?Suzanne Vega: My mind works in a metaphorical way. It’s easier for me to say what I see than what I feel. The emotions are expressed in the images. I think it must be genetic, because my daughter, Ruby, thinks the same way. She’ll see smoke coming out of the back end of a car and say, "The smoke is tap-dancing." And if you look at it, you can see what she means. http://www.acousticguitar.com/issues/ag110/feature110.html6MCB 140, 12-8-06The God Gene“Modern science is turning up a possible reason why the religious right is flourishing and secular liberals aren’t: instinct. It turns out that our DNA may predispose humans towards religious faith. … Dean Hamer, a prominent American geneticist, even identifies a particular gene, VMAT2, that he says may be involved. People with one variant of this gene tend to be more spiritual, he found.”N. Kristof, New York Times, 2-12-057MCB 140, 12-8-06“Nature vs. nurture”:the curse of “folk wisdom”Is a given human trait in a given person the result of “genes or the environment”?•“She got her brains from her Dad”•“Crime runs in his family – it’s genetic…”•“All Klingons are bellicose” (“Blood tells”)•“… is genetically predisposed to …”8MCB 140, 12-8-06In a population, phenotypes of individuals for a quantitative trait tend to be normally distributed9MCB 140, 12-8-06Central limit theorem Carl Friedrich Gauss If a variable is the sum of many independent variables, then its distribution will be normal:ex210MCB 140, 12-8-06In this example, a trait (color) is controlled by three loci, A, B, and C, each of which occurs in only 2 alleles. The actions of the alleles is somewhat additive, in other words, an aabbcc organism is all white, whereas an AABBCC organism is dark red.The remarkable thing is, even with such a simple system (three loci with two alleles each!), we can get a remarkably “smooth” distribution of phenotypes!11MCB 140, 12-8-06Crisper distinction between Mendelian and quantitative traits:For a quantitative trait, the range of phenotypes exhibited by individuals in any given genotypic class is BROADER than the difference between two average individuals of two different genotypes. In contrast, for a Mendelian trait, two individuals of the same genotype will tend to be relatively similar, and all quite strikingly distinct from individuals of a different genotypic class.12MCB 140, 12-8-06Is trait X heritable?Height – yes.Language – no.Neuroticism – ?13MCB 140, 12-8-06PellagraDisorder caused in large part by ???, and characterized by skin lesions and by gastrointestinal and neurological disturbances--the so-called classical three Ds of pellagra: dermatitis, diarrhea, and dementia. Pellagra Commission
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