11MCB 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, 2-12-0527MCB 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:ex−210MCB 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 – ?313MCB 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 (1910s): simple Mendelian inheritance of pellagra in the US South. “Controversy over the origins of pellagra continued until the mid-1930's…”Pellagra is caused by a dietary deficiency ofniacin (nicotinamide and nicotinic acid) –precursor to NAD and NADPPellagra ran in families because poverty ran in families, and poor families in the South subsisted on corn, which is low in niacin.14MCB 140, 12-8-06Is a trait heritable?Well, let’s mate individuals from the two extremes of the distribution, place their progeny into a common, controlled environment, and look.If the progeny follow a distribution that is skewed from the parental one towards the end of the curve their parents came from, the trait is heritable.If the progeny follow the same distribution as the original one, the trait is not heritable.15MCB 140, 12-8-06Mapping of quantitative trait loci (QTLs)“Search for genes responsible for variance in quantitative traits”16MCB 140, 12-8-06Ulrike Heberlein:the inebriometer →Moore et al. (1998)Cell 93: 997.17MCB 140, 12-8-06QTL mapping, version 1Testing alleles of candidate genes (forward genetics): pick a gene (serotonin receptor) that may have something to do with the trait under study (neuroticism) and look for allelic forms thereof that may occur more frequently in individuals who are neurotic.How do you measure someone’s level of neuroticism?http://cac.psu.edu/~j5j/test/ipipneo1.htm18MCB 140, 12-8-06“Mood disorders”: anxiety• Serotonin (5-HT) – neurotransmitter (motor activity, food intake, sleep, reproductive activity, cognition, emotional states, including mood and anxiety).• Serotonin transporter (5-HT uptake) – two alleles (long and short) – former transcribed more efficiently• “NEO personality inventory” – people with short allele have greater anxiety- related personality characteristics• Polymorphism explains 7-9%of genetic varianceLesch et al. (1996) Science 274: 1527.419MCB 140, 12-8-06“Serotonin transporter genetic variation and the response of the human amygdala”“Individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression
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