Quantitative Genetics MCB 140 12 8 06 1 A loose distinction Qualitative traits Blood groups ABO Coat color in cats Color vision Quantitative traits Height Weight Facial features Difference 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 F1 The 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 F1 MCB 140 12 8 06 2 Gene 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 C8 MCB 140 12 8 06 3 New York Times Nov 20 2003 p C8 MCB 140 12 8 06 4 Gene 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 tapdancing And if you look at it you can see what she means http www acousticguitar com issues ag110 feature110 html MCB 140 12 8 06 5 The 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 05 MCB 140 12 8 06 6 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 MCB 140 12 8 06 7 In a population phenotypes of individuals for a quantitative trait tend to be normally distributed MCB 140 12 8 06 8 Central limit theorem Carl Friedrich Gauss If a variable is the sum of many independent variables then its distribution will be normal e x 2 MCB 140 12 8 06 9 In 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 MCB 140 12 8 06 10 Crisper 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 MCB 140 12 8 06 11 Is trait X heritable Height yes Language no Neuroticism MCB 140 12 8 06 12 Pellagra Disorder 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 of niacin nicotinamide and nicotinic acid precursor to NAD and NADP Pellagra ran in families because poverty ran in families and poor families in the South subsisted on corn which is low in niacin MCB 140 12 8 06 13 Is 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 MCB 140 12 8 06 14 Mapping of quantitative trait loci QTLs Search for genes responsible for variance in quantitative traits MCB 140 12 8 06 15 Ulrike Heberlein the inebriometer Moore et al 1998 Cell 93 997 MCB 140 12 8 06 16 QTL mapping version 1 Testing 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 htm MCB 140 12 8 06 17 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 variance Lesch et al 1996 Science 274 1527 MCB 140 12 8 06 18 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 and function and increased fear and anxietyrelated behaviors exhibit greater amygdala neuronal activity as assessed by BOLD functional magnetic resonance imaging in response to fearful stimuli compared with individuals homozygous for the long allele These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and
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