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The Meaning of Race in MedicineThe Meaning of Race in Medicine1212thth Annual Summer Public Health ResearchAnnual Summer Public Health Research

Videoconference on Minority HealthVideoconference on Minority HealthUniversity of North Carolina at Chapel HillUniversity of North Carolina at Chapel HillSchool of Public HealthSchool of Public HealthJune 26, 2006June 26, 2006

Dr. Joseph L. Graves, Jr.Dr. Joseph L. Graves, Jr.Dean, University Studies & Professor of Biological Sciences, Dean, University Studies & Professor of Biological Sciences, North Carolina A& T State University.North Carolina A& T State University.

Fellow, American Association for the Advancement of Science Fellow, American Association for the Advancement of Science

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For a fuller treatment For a fuller treatment see:see:

J.L. Graves, J.L. Graves, The EmperorThe Emperor’’s New Clothes: Biological Theories of Race s New Clothes: Biological Theories of Race at the Millenniumat the Millennium, Rutgers University Press, 2001, 2005; , Rutgers University Press, 2001, 2005; The Race The Race Myth: Why We Pretend Race Exists in AmericaMyth: Why We Pretend Race Exists in America, Dutton Press, author, Dutton Press, author’’s s preface to the soft cover edition, 2005.preface to the soft cover edition, 2005.

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Note on Definitions: Note on Definitions: Biological RaceBiological Race

morphology (phenotype)morphology (phenotype)Geographical locationGeographical locationPopulation based (frequency of genes)Population based (frequency of genes)

Socially Constructed Race: Arbitrarily utilizes aspects of morphology, geography, culture, language, religion, etc. in the service of asocial dominance hierarchy.

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CarolusCarolus Linnaeus Linnaeus -- 17351735Introduces binomial classification system for Introduces binomial classification system for organisms. He describes four suborganisms. He describes four sub--species of species of humans: humans: Homo sapiensHomo sapiens americanusamericanus,, the the Americas; Americas; Homo sapiensHomo sapiens europaeuseuropaeus,, Europeans; Europeans; Homo sapiensHomo sapiens asiaticusasiaticus,, Asians; and Asians; and Homo Homo sapienssapiens aferafer,, Africans. Africans. He did not explain how or why these groups are He did not explain how or why these groups are different. He also includes different. He also includes Homo sapiens Homo sapiens monstrosusmonstrosus, , which included people with which included people with deformities, mythological giants, and the deformities, mythological giants, and the KhoikhoiKhoikhoipeople of southern Africa; and people of southern Africa; and Homo sapiens Homo sapiens ferusferus,, which described wild children found which described wild children found abandoned in forests. abandoned in forests. Relies on morphological/behavioral features, Relies on morphological/behavioral features, Europeans are gentle, optimistic and inventive, Europeans are gentle, optimistic and inventive, while Asians are stiff and greedy.while Asians are stiff and greedy.

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Naturalists of the 19Naturalists of the 19thth century naturalists century naturalists used morphological traits to classify races:used morphological traits to classify races:

Darwin doubted whether Darwin doubted whether human races were real.human races were real.Describes the racial Describes the racial multiplication problem, 2 multiplication problem, 2 ––63 races named.63 races named.Calls human races, protean Calls human races, protean or polymorphic, in or polymorphic, in The The Descent of ManDescent of Man, 1871., 1871.Darwin pointed out that Darwin pointed out that most of the physical most of the physical differences noticed by differences noticed by naturalists could not have naturalists could not have any significance, if so they any significance, if so they would have been removed would have been removed by natural selection.by natural selection.

Charles DarwinCharles Darwin

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LinneausLinneaus and the 19and the 19thth century naturalists were wrong century naturalists were wrong because phenotypic characters are discordant.because phenotypic characters are discordant.

The physical features used to The physical features used to define Americadefine America’’s social races s social races do not reveal our do not reveal our evolutionary history, evolutionary history, CavalliCavalli--Sforza and Edwards 1964, Sforza and Edwards 1964, and Montagu 1974.and Montagu 1974.Genes that control skin color Genes that control skin color are not linked to those that are not linked to those that determine skull shape or determine skull shape or body proportions.body proportions.Fig 2.2.3, Cavalli-Sfroza, Menozzi,

and Piazza., 1994

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Populations have different Populations have different combinations of physical traits.combinations of physical traits.

The failure of physical variation to The failure of physical variation to define races occurs because different define races occurs because different portions of the genome are selected portions of the genome are selected by different factors in any given by different factors in any given environment.environment.For example, solar intensity may For example, solar intensity may change consistently along a N change consistently along a N –– S S gradient, this may impact some gradient, this may impact some genetic systems, but not others.genetic systems, but not others.Meanwhile, other portions of the Meanwhile, other portions of the genome may be impacted by the genome may be impacted by the presence of a specific parasitic presence of a specific parasitic disease, different diets, different rain disease, different diets, different rain fall, or altitude.fall, or altitude.

8UNESCO Statement of 1950UNESCO Statement of 1950

Racial doctrine is the outcome of a Racial doctrine is the outcome of a fundamentally irrational system of fundamentally irrational system of thought and is in glaring conflict thought and is in glaring conflict with the whole humanist tradition with the whole humanist tradition of our civilization. It sets at of our civilization. It sets at noughtnought everything that UNESCO everything that UNESCO stands for and endeavors to stands for and endeavors to defend. By virtue of its very defend. By virtue of its very Constitution, UNESCO must face Constitution, UNESCO must face the racial problemthe racial problem……

In the body:In the body: From the From the biological standpoint, the species biological standpoint, the species Homo sapiensHomo sapiens is made up of a is made up of a number of populations, each of number of populations, each of which differs from the others in which differs from the others in the frequency of one or more the frequency of one or more genesgenes……New York Times, July 17, 1950

From the Preamble

By 1950 serious doubt existed concerning both morphological and geographical conceptions of race.

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Population subdivision is weak in humans.Population subdivision is weak in humans.Compared to other large Compared to other large bodied mammals, bodied mammals, humans have little humans have little genetic differentiation genetic differentiation between their between their populations.populations.Humans have Humans have considerable genetic considerable genetic overlap across the overlap across the genome genome ---- We have also We have also maintained relatively high maintained relatively high levels of gene flow levels of gene flow throughout our history, throughout our history, WrightWright’’s Fs FSTST = 0.156.= 0.156.

Black bar represents humans compared to other mammals, such as white tailed deer, gray wolves, or Grant’s gazelle; data from Templeton (1998, 2002.)

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Estimate of gene flow between human Estimate of gene flow between human subpopulationssubpopulations WrightWright’’s s FFstst for human data = for human data =

0.1560.156We can calculate the effective We can calculate the effective population size and the population size and the migration rate for humans by migration rate for humans by the equation: the equation: FFstst = 1/(4Nm + 1)= 1/(4Nm + 1)Thus Nm = 1.35Thus Nm = 1.35Thus modern human genetic Thus modern human genetic diversity can be explained by diversity can be explained by the long term average of 1.35 the long term average of 1.35 individuals per 25 years, or individuals per 25 years, or 13.5 per 250 years, or 135 per 13.5 per 250 years, or 135 per 2,500 years.2,500 years.Thus sporadic movements that Thus sporadic movements that over long periods of time that over long periods of time that average out to these values average out to these values could easily explain human could easily explain human genetic diversity.genetic diversity.

Fig. 2.15.1, Fig. 2.15.1, CavalliCavalli--SfrozaSfroza, , MenozziMenozzi, and Piazza 1994., and Piazza 1994.

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Isolation by distanceIsolation by distanceHumans best fit a gene

flow, isolation by distance model, Templeton, 2002.

This means that human populations that live closest to each other, share the most genetic variation in common.

Figure 2.3 Templeton 2002

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Human migration 101Human migration 101Anatomically modern humans Anatomically modern humans evolve in Africa > 160,000 evolve in Africa > 160,000 ybpybp..Some leave Africa sometime Some leave Africa sometime around 75,000 around 75,000 -- 55,000 55,000 ybpybp..Replace Neanderthals in Replace Neanderthals in Europe and archaic humans Europe and archaic humans around the world.around the world.Arrive in Western hemisphere Arrive in Western hemisphere between 34,000 and 18,000 between 34,000 and 18,000 ybpybp..Multiple migrations in different Multiple migrations in different prepre--historic periods, followed historic periods, followed by different migrations in by different migrations in historical periods.historical periods.

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Most genetic variation is shared between Most genetic variation is shared between geographically separated populationsgeographically separated populations

Figure 1. Apportionment of Human Genetic Diversity

86

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4

Polymorphic alleles found in all world populations, 86%

Polymorphic alleles unique to a given continent, 10%

Polymorphic alleles unique to a specific local population, 4%

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Nucleotide similaritiesNucleotide similarities

Identical twins: 10,000/10,000Identical twins: 10,000/10,000Siblings 9,995/10,000Siblings 9,995/10,000Unrelated individuals: 9,990/10,000Unrelated individuals: 9,990/10,000Human/Chimp: 9,900/10,000Human/Chimp: 9,900/10,000Human/Flowering plant: 6,700/10,000Human/Flowering plant: 6,700/10,000

However, with a genome estimated at 3 billion base pairs,unrelated humans can be different at 3,000,000 base pairs.

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Methods that examine DNA directly reveal more variation than can be seen at the protein level, particularly if portions of the genome that are not coded are included.

Coding sequences produce transfer RNA’s, ribosomal RNA’s, or proteins, while non-coding sequences include introns, regions that flank coding regions, regulatory sites, and pseudogenes.

In Eukaryotes most of the genome is non-coding. For example, it has been estimated that as much as 95% of human DNA is non-coding.

Estimates of genetic distance are dependent upon how they are calculated.

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Genetic changes in introns and pseudogenes (often called “junk DNA”), do not face selection and therefore accumulate mutations freely. Thus, non-coding segments are exceedingly useful for establishing ancestry. This is because due to chance historicalevents, populations can differ in allele frequencies at these loci.

Non-coding DNA and ancestry

82.882.884.684.6139.5139.5migration migration per 2500 per 2500 yrs.yrs.

0.8280.8280.8460.8461.3951.395NNmm

0.2320.2320.2280.2280.1520.152FFstst

AfAf./Am../Am.AfAf./As../As.Af./EuAf./Eu..369 SNP369 SNP

Fst data from Tischkoff and Kidd, 2004

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Non-coding DNA and ancestry II

Rosenberg et al. Science 298, 2002 utilized an algorithm called structure.They examined the sequences of individuals from various populations andShowed they could be clustered in a variety of ways.

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Non-coding DNA and ancestry IIITischkoff and Kidd 2004, Least Squared tree for 37 populations, using 80 loci with ~ 620 alleles. The populations used are described in Allele Frequency Database(ALFRED). However, ALFRED is still very incomplete, missing suitable data on many regions of the world, including North Africa. In addition, the populations had different characteristics, some were indigenous, while others had greater amounts of admixture.

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Within Population Distribution in the Genetically Defined Clusters of Wilson et al. 2001.

3%73%

3%21%Afro-Caribbean

2%1%95%

2%Papua, NG

84%1%5%9%Chinese

5%2%4%90%Armenian

1%1%2%96%Norwegian

6%24%

8%62%Ethiopian

2%1%1%96%Ashkenazi

2%93%

2%4%Bantu

DCBAPopulation Wilson et. al. in Nature Genetics, 29: 265-69, 2001 using a panel of 39 microsatellite markers showed that genetic variants of drug metabolizing enzymes can be clustered into four groups.

However the four groups did not match the common social definitions of race.

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Actual membership in B ClusterActual membership in B Cluster

1.01.0AfroAfro--CaribbeanCaribbean6.06.0Papua, NGPapua, NG83.083.0ChineseChinese< 1.0< 1.0ArmenianArmenian< 1.0< 1.0NorwegianNorwegian7.07.0EthiopianEthiopian< 1.0< 1.0AshkenaziAshkenazi2.02.0BantuBantuPercentPercentPopulationPopulation This is true because the

population sizes are different. Thus every genetically defined cluster will have significant numbers of Chinese, simply due to China’s size.If other populations are included, such as India, these figures would shift again.

Thus, we should expect all suitably large populations to have people from all drug metabolizing clusters.

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Greater numbers of Greater numbers of microsatellitemicrosatellite markers (326) were able markers (326) were able to correlate selfto correlate self--identification with genetic clustering.identification with genetic clustering.

9021Other

001600Jap.

004070Chin. Am. & Taiwanese

411001Mex. Am.

01,30503Af. Am.

1001,348Eu. Am.

DCBASIRE

Tang, et al. 2005 used Structure with K = 2, 3, 4 or more clusters. When K = 2, Chinese/Japanese emerged as a group from all others, K = 3, gives African Am., Eu. Am. & Mex. Am., & Chinese/Japanese; and K = 4 is shown above.

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Structuring nonStructuring non--coding genetic variation weakly revealed coding genetic variation weakly revealed candidate markers for hypertension.candidate markers for hypertension.

Mean0.05075961309Total

11730.04855164Maywood, IL

17530.04238961Jackson, MS

10550.05814949Forsyth, NC

17990.05536835Birmingham, AL

TestedProp.

Sig.Afr. Hyp.Afr.

Norm

Approximately 5% of the markers tested showed any significant difference between normatensive and hypertensive individuals. For the Chinese sample itWas about 4.4%, Mexican American 5.7%, and European American about 4.3%.

The paper did not report whether the significant markers were similar for all Populations tested.

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Gene Flow & AdmixtureGene Flow & AdmixtureThere is a wide variety of admixture There is a wide variety of admixture percentages in North Americans with percentages in North Americans with African descent.African descent.Recent measures suggest that the average Recent measures suggest that the average African Americans has on average 17 African Americans has on average 17 --20% European admixture.20% European admixture.Also there could be as much as 10% Also there could be as much as 10% American Indian admixture.American Indian admixture.Therefore, could be as much as a 30% Therefore, could be as much as a 30% probability of African American genetic probability of African American genetic predisposition actually originated in Asians predisposition actually originated in Asians and Europeans.and Europeans.Remember also that Asians and Europeans Remember also that Asians and Europeans began their genetic odyssey in Africa, began their genetic odyssey in Africa, hence at any specific locus, a European or hence at any specific locus, a European or Asian may have an allele that was Asian may have an allele that was originally African, as opposed to one that originally African, as opposed to one that originated outside of Africa.originated outside of Africa.

Only 6% of the individualsin this study who self-identifiedas African American had a majorityof their genetic markers indicatingAfrican Origin – this would differ by region.However, 93% of self-identified European Americans had the majorityof their genetic markers originating inEurope.Self identified American Indians wouldshow the African American pattern and at present, self-identified Asian Americans would show the European pattern, Sinha et al. 2006, NEJM, 354(4): 421-22.

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However, populations differ in specific coding gene However, populations differ in specific coding gene frequencies:frequencies: phenylketonuriaphenylketonuria –– mechanism, mechanism, mutation/selection balance or genetic drift.mutation/selection balance or genetic drift.

1/10,0001/10,000USA (total)USA (total)

1/10,0001/10,000USA (EuroUSA (Euro--Americans)Americans)

1/2,6001/2,600TurksTurks

1/30,0001/30,000SwedesSwedes

1/119,0001/119,000JapaneseJapanese

1/5,0001/5,000Irish, Scottish, Yemenite JewsIrish, Scottish, Yemenite Jews

1/16,0001/16,000ChineseChinese

Note, that while the Chinese and Japanese belong to the same genetic clusteras determined by SNP’s, they differ in orders of magnitude in phenylketonuriafrequency and while Nigerians and Icelanders are in different clusters they have near identical frequencies of blood group O.

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Attenuated responses to multiple vasodilators commonly observed in AA’s. Mechanism not understood.

Consistent difference but no physiological basis shown.

27 AA, 27 EU, 18AA, 18 EU, 9 AA, 13 EU and 16

Beta-adrenoceptorgonist

Increased predisposition in AA to salt-sensitive form of essential hypertension.

Reasonable physiological basis

1,105Calcium-channel blocker

Related to lower bioactivity of nitric oxideReasonable physiological basis

225 AA, 280 EUThiazide(diuretic)

No mechanism, and study not replicated.Possibly false positive1,105Beta-adrenoreceptorblocker (β1-selective)

R389G polymorphism in β1 adrenergic receptor.

Genetic causation indicated

365 AA&EU, 2708Beta-adrenoreceptorblocker

Attenuated responses commonly seen in AA, but mechanism not understood.

Consistent difference but no physiological basis shown.

11 AA, 9Eu, 21AA, 19 Eu

Vasodilator antihypertensive

Related to lower bioactivity of nitric oxideReasonable physiological basis

180AA, 450 Eu, 215 AA, 574 Eu

BiDil

Related to lower bioactivity of nitric oxideReasonable physiological basis

1,196 Eu, 800 AA, 124 Eu, 207 Eu, 91 AA

Ace Inhibiters

EvidenceIs it real?NDrug Class

Summarized from Table 1, Tate and Goldstein, Nature Genetics 2004

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Sampling scheme alone is enough to doubt any “racial” interpretation of this data.

1 genetic, 5 reasonable physiological, 5 consistent no, 4 false positives.

> 22,000 Eu, ~6,000 AA, 22 Am. Ind., 72 As., & 28 His.

Totals

Conflicting results.Possibly false positive8 As, 40 Eu, 22 Am. Ind.Analgesic

Drug polymorphism has not been reliably associated with Eu & As; different prescribing practices for populations.

Consistent difference but no physiological basis shown & false positive

~288 Eu, 800 AA, 65 AsAntipsychotic

Differences remain after adjusting for body fat, mechanism unknown.

Consistent difference but no physiological basis shown.

14 Eu, 15 AA, 28 HisInsulin

Probably due to differences in health care, some experiments not replicated.

Possibly false positive~14,000 Eu, 1500 His, 167 As, 1000 AA

Cytotoxic agents

Not replicated and no supporting evidence.Possibly false positive1381Prostaglandin analog

May be due to different immune abilities, AA produce more cytokine than Eu.

Reasonable physiological basis

100AA, 100 Eu, 4031 AA, 62 Eu

Hepatitis Antiviral Treatment

Altered pharmocogenetics between AA and EUConsistent difference but no physiological basis shown.

9 Eu, 9 AAGlucocorticoid

EvidenceIs it real?NDrug Class

Summarized from Table 1, Tate and Goldstein, Nature Genetics 2004

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End NotesEnd Notes

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The intellectual program of social The intellectual program of social dominancedominance

The history of all hitherto existing society, is the history of The history of all hitherto existing society, is the history of individual individual and groups of males attempting to suband groups of males attempting to sub--ordinate other males and ordinate other males and females (social dominance.)females (social dominance.)Hierarchical society may have been fixed in our primate lineage:Hierarchical society may have been fixed in our primate lineage:Orangutans, Gorillas, Chimpanzees, and humans.Orangutans, Gorillas, Chimpanzees, and humans.Found in all societies that produced a social surplus, such as Found in all societies that produced a social surplus, such as Egyptian, Greek, Roman, Aztec, Chinese, Japanese, etc.Egyptian, Greek, Roman, Aztec, Chinese, Japanese, etc.Intellectual programs were developed to justify some groups Intellectual programs were developed to justify some groups garnering more of the societygarnering more of the society’’s production than others. This s production than others. This ultimately translated into that groupultimately translated into that group’’s greater material wells greater material well--being, being, such as health, emotional satisfaction, and reproductive advantasuch as health, emotional satisfaction, and reproductive advantage.ge.

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Any genetic explanation of intelligence Any genetic explanation of intelligence would require that environments were would require that environments were equalized.equalized.

No such equality of environments No such equality of environments exists or has ever existed for exists or has ever existed for minorities in America.minorities in America.

Furthermore, this is impossible Furthermore, this is impossible since by definition the social since by definition the social environment of minorities must environment of minorities must be different from that of be different from that of majorities.majorities.

The environments are made even The environments are made even more disparatemore disparate by the social by the social dominance of the European dominance of the European population.population.

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Affirmative action for the dominant Affirmative action for the dominant populationpopulation

The vast majority of federal and The vast majority of federal and state government actions have state government actions have differentially benefited people of differentially benefited people of European descent.European descent.Consider the Indian Removal Act Consider the Indian Removal Act of 1830, the five civilized tribes of 1830, the five civilized tribes were forced to give up the land were forced to give up the land that now comprises most of that now comprises most of Tennessee, Georgia, Kentucky, and Tennessee, Georgia, Kentucky, and Mississippi.Mississippi.They were forcibly moved west of They were forcibly moved west of the Mississippi River, 4,000 of the Mississippi River, 4,000 of 18,000 died during the 18,000 died during the ““trail of trail of tears.tears.””They were promised this land, They were promised this land, ““as as long as the waters run and the long as the waters run and the grasses grow.grasses grow.”” Well we know Well we know what happened to that promise. what happened to that promise.

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Give me your huddled masses: so long Give me your huddled masses: so long as they are as they are ““white.white.””

US immigration policy was biased US immigration policy was biased toward toward ““racesraces”” that could be that could be assimilated into America.assimilated into America.This meant in practice that 19This meant in practice that 19thth

century immigration was to match century immigration was to match the composition of the country in the composition of the country in the 1824 census (mainly Anglothe 1824 census (mainly Anglo--Saxons, Irish, Swedes, Germans, Saxons, Irish, Swedes, Germans, and other northern Europeans.and other northern Europeans.After slave importation stopped, After slave importation stopped, there was virtually no legal there was virtually no legal immigration of Africans or Afroimmigration of Africans or Afro--CaribbeansCaribbeans..Congress passed the Chinese Congress passed the Chinese Exclusion Act in 1880.Exclusion Act in 1880.Japanese immigration to the US Japanese immigration to the US

begins in earnest in the early 20begins in earnest in the early 20thth

century.century. 11.23,300,000Russian

7.82,300,000Scandanavians

14.34,200,000Austria-

Hungary

14.34,200,000England

16.24,750,000Italian

15.34,500,000Irish

20.56,000,000German

PercentNumbersPopulation

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Governmental action creates modern Governmental action creates modern America, leaves out nonAmerica, leaves out non--whiteswhites

Housing act of 1949 Housing act of 1949 makes homes affordable makes homes affordable for the first time.for the first time.Between 1934 Between 1934 –– 1962, 1962, FHA guarantees 120 FHA guarantees 120 billion dollars of home billion dollars of home loans.loans.Less than 2% are made Less than 2% are made to nonto non--whites.whites.The suburbs are born, The suburbs are born, housing values are housing values are determined by how determined by how ““whitewhite”” your your neighborhood is.neighborhood is.

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Social dominance can increase risk of toxic Social dominance can increase risk of toxic exposure.exposure.

3.573.572.032.033.043.04Superfund sites/per sq. mileSuperfund sites/per sq. mile

5.005.002.382.383.683.68Facilities emitting criteria air Facilities emitting criteria air pollutantspollutants

1.471.471.311.311.501.50Cancer risk from hazardous air Cancer risk from hazardous air pollutantspollutants

1.561.561.541.541.431.43Releases of toxic chemicalsReleases of toxic chemicals

RatioRatioby by ownershipownership

RatioRatioby by IncomeIncome

RatioRatioby raceby race

Source: Source: www.scorecard.orgwww.scorecard.orgIncome = high v. lowIncome = high v. lowOwnership = owners and nonOwnership = owners and non--ownersowners

Race/ethnicity, income, and home ownership (NJ, 2003.)Race/ethnicity, income, and home ownership (NJ, 2003.)

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Social hierarchy harms those who Social hierarchy harms those who are dominatedare dominated

Neuroscience has begun to look at many Neuroscience has begun to look at many genetic variants between individuals that genetic variants between individuals that correlate to behavior, such as addiction.correlate to behavior, such as addiction.Cocaine addiction is linked to dopamine Cocaine addiction is linked to dopamine transporters, genetic variation exists in transporters, genetic variation exists in humans at these loci.humans at these loci.

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One type of such harm has been shown One type of such harm has been shown experimentally in other primatesexperimentally in other primates

Social subordinate Macaques Social subordinate Macaques were more likely to selfwere more likely to self--administer cocaine administer cocaine (addiction.)(addiction.)This was lower in monkeys This was lower in monkeys housed alone or who were housed alone or who were socially dominant.socially dominant.African American college African American college students who reported students who reported suffering racist harassment suffering racist harassment were twice as likely to use were twice as likely to use tobacco daily, Bennett et al. tobacco daily, Bennett et al. 2005, AJPH.2005, AJPH. Morgan et. al. Nature Neuroscience,

Vol. 5 No. 2, February 2002.

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The impact of environmental differences The impact of environmental differences is complexis complex

Studies of malnutrition in rats Studies of malnutrition in rats showed that maternal effects on showed that maternal effects on adult health extended over several adult health extended over several generations.generations.We have already seen that We have already seen that differential stress exposure plays a differential stress exposure plays a role in predisposing some African role in predisposing some African Americans to hypertension.Americans to hypertension.Offspring of alcoholic mothers Offspring of alcoholic mothers show FA in their teeth, FA has show FA in their teeth, FA has been linked to lower IQ in college been linked to lower IQ in college students.students.

Numerous studies show that Numerous studies show that lasting adult pathology can lasting adult pathology can result from stress in the result from stress in the maternal environment: Desai maternal environment: Desai et al. 1995; Hales et al. 1996; et al. 1995; Hales et al. 1996; Napoli et al. 1997; Napoli et al. 1997; WaterlandWaterlandand Garza 1999; and Garza 1999; MustilloMustillo, S. , S. et al. 2004; Collins et al., et al. 2004; Collins et al., 2004.2004.Another recent study showed Another recent study showed parental exposure to racial parental exposure to racial discrimination had negative discrimination had negative impacts on the mental health impacts on the mental health of their preof their pre--school aged school aged children, children, CaughyCaughy et al. 2004.et al. 2004.

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Distribution of Sickle Cell Anemia Allele is Distribution of Sickle Cell Anemia Allele is discordant with discordant with ““race.race.””

Distributed at high Distributed at high frequency in frequency in ““NegroidsNegroidsand and CaucasoidsCaucasoids..””Seen as Seen as ““BlackBlack”” disease disease in U.S. due to importation in U.S. due to importation of slaves derived from W. of slaves derived from W. Africa.Africa.

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Malaria in the USAMalaria in the USADid the presence of the allele help Did the presence of the allele help ““BlacksBlacks””fight off malaria relative to fight off malaria relative to ““WhitesWhites”” in North in North America?America?In the early 20In the early 20thth century, an estimate of Blacks century, an estimate of Blacks heterozygous for the sickle cell trait was about heterozygous for the sickle cell trait was about 8%.8%.Yet, in 10 southern states, Blacks suffered Yet, in 10 southern states, Blacks suffered 25/100,000 death rate v. only 7/100,000 for 25/100,000 death rate v. only 7/100,000 for whites in 1921 whites in 1921 –– 1923 (who supposedly did 1923 (who supposedly did not have the allele.)not have the allele.)Grover 1937, J. Negro Education (6), 281.Grover 1937, J. Negro Education (6), 281.

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Genetic variation & hypertensionGenetic variation & hypertension

A number of gene loci A number of gene loci have been associated have been associated with increased risk of with increased risk of hypertension.hypertension.AGT AGT ---- which codes for which codes for angiotensinogenangiotensinogen a protein a protein made by the liver and made by the liver and circulates in excesscirculates in excessACE ACE –– angiotensinangiotensinconverting enzyme converting enzyme

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Genetic variation & hypertension IIGenetic variation & hypertension IIAt the At the angiotensinogenangiotensinogen locus locus the 235T mutant has tyrosine the 235T mutant has tyrosine switched for switched for methioninemethionine..In EuroIn Euro--Americans, 235T is Americans, 235T is associated with an increased associated with an increased risk of hypertension.risk of hypertension.The 235T allele is found at a The 235T allele is found at a frequency of 85% in African frequency of 85% in African Americans.Americans.However, 235T is not However, 235T is not associated with increased associated with increased hypertension risk in Nigerians. hypertension risk in Nigerians. Cooper, Rotimi, Ward 1999, pg. 42.

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Genetic variation & hypertension IIIGenetic variation & hypertension IIIAt the ACE locus there is a common At the ACE locus there is a common alualuinsertion polymorphism that affects the insertion polymorphism that affects the activity of this enzyme.activity of this enzyme.The D allele is characterized by an absence of The D allele is characterized by an absence of these these alualu insertions, and thus have higher insertions, and thus have higher enzymatic activity.enzymatic activity.The available evidence shows that the The available evidence shows that the enzymatic activity of II, ID, and DD enzymatic activity of II, ID, and DD genotypes are similar in Nigerians, genotypes are similar in Nigerians, Jamaicans, and in the United States (all Jamaicans, and in the United States (all populations.)populations.)Hence the deletion genotypic doesnHence the deletion genotypic doesn’’t seem to t seem to be influenced by be influenced by ““racialracial”” background.background.Source: R.S. Cooper (1997).Source: R.S. Cooper (1997).

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Genetic variation and hypertensionGenetic variation and hypertension

There are at least 33 genetic systems with > There are at least 33 genetic systems with > 63 loci involved in hypertension predisposition.63 loci involved in hypertension predisposition.In studies on hypertension published between In studies on hypertension published between 1997 1997 –– 2003, only 2/10 found frequency 2003, only 2/10 found frequency differences in genetic variants in the direction differences in genetic variants in the direction of the proposed health differential.of the proposed health differential.In 8/10 studies, genetic variation In 8/10 studies, genetic variation existed, but it was not in the direction of existed, but it was not in the direction of the hypertension rates seen in America!the hypertension rates seen in America!

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Hypertension IIIHypertension III

Genetic variation in doesnGenetic variation in doesn’’t explain t explain hypertension differentials:hypertension differentials:angiotensinangiotensin converting enzymeconverting enzymeAngiotensinogenAngiotensinogen I and III and IIαα-- and and ββ-- adrenergic receptorsadrenergic receptorsPlasma Plasma kallikreinkallikreinG proteinG protein--b3b3

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b2b2--adrenergic polymorphismsadrenergic polymorphisms The gly16 variant has been associated with hypertension in Afro-Caribbean’s and Norwegians, but not African or European Americans. The frequency of the gly16 variant was slightly higher in European Americans it was not significantly different between the normal and hypertensive in either group.

0.40

0.358

0.379

0.51

0.184

0.347

Hypertensives study 1

Hypertensives study 2

Avg. freq.

0.470.3520.411

0.500.1800.34

Normal study 1Normal study 2Avg. freq.

Eu. Am.frequency

Af. Am.frequency

Gly16 genetic variant

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Hypertension?Hypertension?Actually, when hypertension rates are stratified Actually, when hypertension rates are stratified by socioeconomic status, the differential is by socioeconomic status, the differential is located amongst African Americans in the higher located amongst African Americans in the higher categories.categories.This is means that the hypertension difference This is means that the hypertension difference results from a biological response to results from a biological response to social/cultural factors (e.g. control racism, social/cultural factors (e.g. control racism, reduce hypertension differential.)reduce hypertension differential.)NeserNeser et al. 1986; Broman 1989; Calhoun 1992; et al. 1986; Broman 1989; Calhoun 1992; Light 1995. Light 1995.

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Irrational resuscitation of raceIrrational resuscitation of raceActually Wilson et al. examined population samples from Actually Wilson et al. examined population samples from around the world including: Norwegians; Ashkenazi Jews; around the world including: Norwegians; Ashkenazi Jews; Armenians; South China; Papua, NG; East and West Africa; Armenians; South China; Papua, NG; East and West Africa; and Afroand Afro--CarribeansCarribeans..They found that 4/6 genetic variants they examined could They found that 4/6 genetic variants they examined could be formed into four clusters.be formed into four clusters.This, of course means that 2/6 could not be clustered! (a This, of course means that 2/6 could not be clustered! (a fact not mentioned by fact not mentioned by RischRisch.).)Most importantly, Wilson et al. concluded that the Most importantly, Wilson et al. concluded that the four genetic clusters they discovered, did not match, four genetic clusters they discovered, did not match, socially constructed race or ethnicity (again a fact socially constructed race or ethnicity (again a fact not mentioned by either not mentioned by either RischRisch or Wade.)or Wade.)Goldstein and Goldstein and ChkhiChkhi 2002 interpret Wilson et al.: 2002 interpret Wilson et al.: ““races in any meaningful sense of the term do not races in any meaningful sense of the term do not exist in the human speciesexist in the human species…”…”, An. Rev. Genomics , An. Rev. Genomics and Human Genetics, vol. 3and Human Genetics, vol. 3

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Distribution of Sickle Cell Anemia Allele is Distribution of Sickle Cell Anemia Allele is discordant with discordant with ““race.race.””

The origin of the allele is The origin of the allele is uncertain.uncertain.However it is distributed However it is distributed at high frequency in at high frequency in ““NegroidsNegroids and and CaucasoidsCaucasoids..””High altitude Kenyans High altitude Kenyans dondon’’t have any sickle cell.t have any sickle cell.Seen as Seen as ““BlackBlack”” disease disease in U.S. due to importation in U.S. due to importation of slaves derived from W. of slaves derived from W. Africa were malaria was Africa were malaria was prevalent.prevalent.

Fig. 5.8, Ridley 1996

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Polymorphic loci vary in frequencyPolymorphic loci vary in frequencyPolymorphic loci have Polymorphic loci have numerous alleles, with no numerous alleles, with no single allele at a single allele at a frequency > 99%.frequency > 99%.PhenylketonuriaPhenylketonuria, q = 0.01, q = 0.01TayTay Sachs A, q = 0.017Sachs A, q = 0.017Cystic Fibrosis, q =0.022Cystic Fibrosis, q =0.022Sickle Cell Anemia, q = Sickle Cell Anemia, q = 0.0500.050

Distribution of CF Δ F-508 allele, Fig. 2.14.10, Cavalli-Sforza, Menozzi,and Piazza, 1994.

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