Modern Human Physical Variation
Modern Human Physical Variation ANTHROP 301
Popular in Course
Popular in anthropology, evolution, sphr
This 58 page Class Notes was uploaded by Shad Lehner on Monday September 21, 2015. The Class Notes belongs to ANTHROP 301 at Ohio State University taught by Douglas Crews in Fall. Since its upload, it has received 59 views. For similar materials see /class/209973/anthrop-301-ohio-state-university in anthropology, evolution, sphr at Ohio State University.
Reviews for Modern Human Physical Variation
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 09/21/15
Ly 301 Notes Human Variation anything that differs Tanningvariation and plasticity ability to respond to an environment with variety of phenotypes short term acclimatization Darwin Perpetual change Common descent Multiplication of species Gradualism Natural Selection Perpetual Change Organisms undergo modi cations across generations thru time Documented by fossil record Common Descent All forms of life are descended from a common ancestor thru a branching of lineages Supported by ubiquity of DNA and genetic code biochemicalphysiological similarities and by comparative studies of cell structure and homologous morphologies e g vertebrate skeleton Multiplication of species Evolution proceeds by splitting and transforming older ones Do not interbreed Gradualism Large differences in traits that distinguish species by accumulation of many incremental changes Darwin didn t understand the genetics involved iPunctuated equilibrium Natural Selection Populations accumulate favorable characterizes over time to facilitate J 39 to 39 sur 39 J 39 struggle for existence Must be differential survive and reprod Generate new adaptations and new species IVU GeneUnit of heredity that governs a particular trait Epistasis2 or more genes controlling a phenotype CistronSmallest piece of DNA that codes HeretabilityDegree to which a quantitative phenotype is due to the additive effects of genes VNTRVariable number tandem report chromosomal regions in which a short DNA sequence motif is repeated a variablen umber of times at a single location RFLPRestriction fragment length polymorphisms new type of dna markers not coded HLNMHCHuman leukocyte antigen systemmajor histocompatibility complex Presents foreign antigens to leukocytes MultifactorialMany factors governing a single phenotype env culture genetics Genetic Polymorphismhaving more than 1 type of allele present in a population at a frequency greater than the mutation rate PolygenicA trait determined by more than one locus Postulatea rule accepted without proof Lawsequence of events in nature that has been observed under the same conditions gravity 301 Notes 10609 Simple Traits Mostly Genetic Are not generally in uenced by environment or culture All Mendelian traits are simple traits Complex Traits Typically involve an interaction between genetics environment and culture Pleiotropy one gene with multiple phenotypes sickle cell anemia PKU Epistasis gene to gene interaction one gene s effect will be masked and the other enhanced Proteiome gt geneome 30000 gt 23000 Mendelian Trats Hitchikers thumb Tongue roller free earlobes left thumb overlap albinism 301 Notes 101309 Complex Traits Human Intelligence and IQ Complex Traits In uenced by genes environment and culture Phenotypes are displayed in a continuous series that can be quantified whereas simple traits are qualitative this or that More than just genes contribute to a trait polygenic and Multifactorial Ex Of complex traits Male pattern baldness polygenic Not merely a simple trait carried on the xchromosome Human Eye color affected by multiple loci also effected by environment diet and culture ie contacts De nition of complex traits Multilocus polygenic traits Quantitative trait loci QTL Govern a single trait but may be located on different chromosomes Exhibit continuous distribution displayed by a bell shaped curve Range of phenotypesiplasticity ability of individual to adapt to environmental stressors by changing your phenotype norm of reaction The pattern of phenotypes produced by a given genotype under different environmental conditions Multifactorial In uenced by genes environment and culture Inherited as genetic potential propensity predisposition that can be modified ex Two twins who were separated at birth one lives in closet other normal conditions Closet one grows only to 4 ft normal one 6ft what is governing this Nature vs Nurture Heritability hAZ variation due to genes not inheritance does not apply to simple traits The ADDITIVE variation Doesn t account for epitasis pleitropy etcgene gene interaction Vartotal 7 VareVartotal Proportion of Vargen NEED TO MEMORIZE Non genetic real world example Total of points you can get in class lOOpoints missed20 80100 80 May have penetrance degree to which the genotype shows up in the phenotype Take home message Most human traits are complex traits being governed quantitatively by many genes along with environment and culture However not all complex traits are in uenced by the environment and or culture some genetic patterns that show very complex phenotypes but are really due to genes ex mental retardation Such examples are Number of vertebrae 24 avg Positioning of the eyes 4 chambered heart Human skin color and height Skin Color Four diallelic 2 alleleslocus and codominance each allele shows up loci equivalents to determine skin color by equivalent we mean there may be more loci involved but the results can be explained by only 4 Height 6 diallelic loci Cardiac Disease Hypercholesterolemia H ertension Glycemia Fer lity Normal Population Distribution Multivariate Normal Density mimy D I wrdinury exirnnrdinnry Inns and Inns nfvuies Meanmedianmode in a totally normal curve Meanaverage MedianNumber in the middle ofthe distribution Modernost frequent number in the distribution In a normal distribution Ifthe mean ofa second population is outside 2 standard deviations from the mean of the rst population the two groups represent distinct populations 1 std dev includes 68 ofpop 2 std dev includes 95 ofthe pop 3 std dev includes 99 ofthe pop Examples A systolic pressure of 160 Was said to be hypertension This value Was gt2 standard deviations from the mean of blood pressure A cholesterol value of 240 Was said to be too high because it exceed 2 standard deviations Scientisw initially moved this value to 200 Currently the value is 180 Anthropometry human measuremenw e nition a measurement ofhuman body form An ectomorph is slenderlinear A mesomoph is mediummuscular An endomorph is heavyobvious fat deposits Plasticity Changing your phenotype during your lifetime by modifying environmental andor cultural factors Plasticity allows a range of variation beyond the genes Plasticity may be adaptation Heritability H H02 h02 Definition Proportion of phenotypic variation that is due to additive genetic c factors Only applies to quantitative variation complex traits of the sample which is measured Represents the cumulative effect of all quantitative loci affecting a trait Is environmentally specific Is always a proportion Is most useful in animal and plant breeding Number of eggs laid per week by a chicken Weight of turkey breast Marbling ofa steak H02variation genes vartotal varenv Variation total vargenes varenv Some Heritabilities From MI Study Fingertip ridge counts90 Heritable IQ 70 Dizygotic twinning50 Female fertility 1020 Phenotypic variation caused by the environment can be estimated by studying monozygotic t wins raised together clones of inbred organisms can also be used any set of relatives if using siblings raised together the values have to be divided by half since siblings are only half related Concordance degree to which monozygotic twins show the same phenotype Vargenesvarsibs or dizygotic twins 7 Varmonozygotic twinsvar total Concordance for NIDDM type 2 diabetes Monozygotic 90 Dizygotic 45 Concordance for IDDM Monozygotic 40 Dizygotic 20 High genetic vs high environmental risks Lower concordancemore likely it is not genetic Equal concordancemore likely that is shared environmental effects Selection The greater the hA2 the less natural selection is controlling trait at a constant value eg birth weight or baby s head size Natural selection Process by which a species slowly becomes more t to a particular environment measured as reproductive success RS Arti cial selection Humans intervene in the selection process to speed it up and x certain traits Penetrance De nition Frequency with which a genotype manifests itself in a given phenotype more common for simple traits Reduced Penetrance is associated with variable age of onset e g late onset of Huntington s disease our ability to recognize expression of the disease Non Penetrance Absence of phenotype in individual known to carry disease gene Traits may skip a generation Ex Red green colorblindness is an xlined trait that shows up in males but generally not in females Norm of Reaction For any genotype there is a range of possible phenotypes quantitative traits Dependent on environment and or culture A trait that is less set in the genes can have a wide norm of reaction The broader the norm of reaction the more natural selection can act on the trait Traits not closely tied to survival and reproductions are apt to be more variable such as adult height and weight Before modern medicine a baby s birth weight was critical too large and the baby could not pass Range of variation for complex traits increases up to a point with age The most variable people in the world are ages 5060 After that traits tend to drop back toward the mean as people closest to the mean survive the longest A form of regression to the mean SUMMARY Simple traits polymorphism pql Nature genes strong in uence Have or do not have Complex Traits Multiple loci involved Heritability plasticity Nature vs nurture Norm of reaction Forces of Evolution and Human Variation 301 23000 coding genes Forces of evolution De nition Upsets the genetic equilibrium to promote evolution 1 Recurring Mutation the ultimate source of genetic variation in populations by making changes in the DNA sequence 2 Genetic drift chance uctuation in allele frequency from one generation to the next due to sampling error eg bottleneck founder effect promoted by a small population size in which inbreeding endogamy occurs 3 Natural selection acts on whole organisms not on isolated traits in the whole population favors individuals whose traits allow them to survive and reproduce better in the current environment to yield viable offspring so that they pass more of their alleles to the next generation reduces the reproductive success of the whole population Directional stabilizing disruptive 4 Migration gene ow movement of alleles into and or out of a population introduction of genes already present in one population to another population ofthe same species prevents populations from diverging by introducing new genetic variation from gene pools outside of the population outcrossing exogamy can involve human movement such as wars colonization and exploration 5 Nonrandom mating assortative mating not technically a force for evolution Does not change allele frequencies but changes genotype and phenotype frequencies preferential mating can channel the genotypes along certain lines promote homozygosity after one gen of non random mating back to hardy Weinberg equilibrium deliberate outcrossing can promote heterozygosity 6 Recombination not among the four standard forces however it creates new variation but it is a mutation the formation of new combinations of linked genes by the occurrence of crossing over between homologous chromosomes during meiosis the shuf ing of genotypes between parents and offspring by independent assortment of alleles during meiosis associated with gamete formation and their pairing into new combinations upon fertilization 9 base pair deletion is a mutation in your mtDNA it is a marker for Asian ancestry Eastern AsiaPolynesiansnative American ancestry Mutation can involve changes at the DNA sequence level microevolution or at the chromosomal level macroevolution Only mutation produces totally new genetic variation Types of mutation 1 Point mutation GC 7 AT Substitution of a single base nucleotide for another Can change the codon to specify a different amino acid 2 Nonsense mutations code for a stop codon which can truncate the protein 3 Missense mutations code for a different amino acid EX Sickle cell Hb 4 Silent mutations code for the same amino acid ie no change in amino acid no change in codon due to mutation 2 Insertion GCAT 7 GCAAT Insertion of one or more base nucleotide into the DNA sequence Changes the reading frame forward of the mutation 3 Deletion GCAT 7GCT Deletion of one or more base nucleotides in the DNA sequence Changes the reading frame backward of the sequence Deletions are responsible for an array of genetic diseases including some cases of male infertility 23 of cases of Duchene muscular dystrophy and cry of the ca syndrome 4 Duplication GCAT 7 GCATGCAT Increases the copy number of stretch of DNA sequence a large insertion Facts Mutation and migration introduce genetic variation into a population whereas genetic drift and natural selection reduce the genetic variation the modern human population is thought to have gone through several genetic bottlenecks Founder s Effect De nition Effect of establishing a new population by a small number of individuals carrying only a small fraction of the original population s genetic variation As a result the new population may be distinctively different both genetically and phenotypically than the parent population from which it is derived type of human migration but random WRT with respect to genotype Migration of people is not random typically migration with family and friends Slaverycould have been fairly random Examples 1 polydactyly is common among Amish who descendants migrated to the US 2 Peopling of the Pitcairn island by the bounty mutineers Island off of Venezuela 7 the incident of Huntington s disease is 50 amp is traceable to a Portuguese sail deserter who mated with a native woman A model for nearsightedness supposes that the bestsighted males were recruited for the military which those with poor eyesight were left at home to mate with women and pass on the myopic trait War disease and environmental catastrophe can all produce bottlenecks that cause genetic drift Population Definition Often referred to as the breeding population Includes individuals who are in a local populations can be defined very narrowly or broadly In epidemiology defined as the denominator AKA in demography as the deme Deme Isolated breeding population EX Amish Basque Most evolution occurs in demes Effective Population Size A HW condition is that there is complete random mating within a population This is not accurate in the real world Ne4n22 sdA2 SdAZvariance in the number of offspring produced Standard deviation sd 7 the square root of the variance For HW to apply no forces of evolution are acting and everybody produces the same number of offspring in infinite breeding populations Important Know how to construct a genetic treeishowing parents offspring and multiple generations A male is represented by a square and a female by a circle Proband the first person in a family that has been indentified as having a condition usually a genetically determined disease Genetic markers have been identi ed along all human chromosomes Usually they do not code for anything and are in the spacer DNA 90 that doesn t code for proteins They frequently can be found to be associated with multiple loci that affect a quantitative trait called quantitative trait loci QTL QTLQuantitative Trait Loci used to find the polymorphisms in underlying traits Multifactorial genes environment culture and polygenicstrictly genetic Finding all the different loci that contribute to a quantitative trait EX Blood pressure 12 major genes Evolutionary force mutation genetic drift natural selection gene ow Variation within a population increases decreases decreases increases Variation between populations increases increases increases decreases Take home message Thus gene ow decreases the genetic variation between populations Balanced polymorphisms Selection where the heterozygote exhibits the greatest fitness in a particular environment Selection against the 2 homozygote s in a simple trait PKU northern Europe sickle cell anemia TaySachs When two or more alleles are occurring at a locus with high frequency and stay at a relatively high rate from generation to generation When any allele reaches 100 it s fixed in a population Transient Polymorphisms Opposed to balanced polymorphisms Frequency of allele 1 at 3 A2 at 3 and A3 at 4 Allele frequencies changing over time due mainly to drift Gives rise to the neutral theory of evolution if every allele were selected against we would never reproduce some believe that most polymorphisms are transient Infinite Alleles model Suggestion that all mutations are new mutations There are in nite numbers of states that an allele can mutate to Hence each mutation is Assumed to be unique The 9bp mtDNA deletion on mitochondrial DNA is a marker for Asian ancestryiit is said to have occurred only once Albinism and PKU 7 have multiple mutations DMD Duchene Muscular Dystrophy fall appear to be newly arisen mutations Discontinuous Variation The variation between populations abruptly changes Example the frequency of 0 allele in ABO in South American Native Americans is about 100 Clinal variation The variation between populations abruptly changes De nition Gradual change over space Changes slowly from place to place Example ABO Going north in North America 0 frequencies decreases Europe 7 it is only about 20 Sickle cell allele is also considered to be Clinal variation Sexual selection De nition type of NS that acts differently on males and females Females choose males Originally suggested by Darwin as cause for racial variation Rare male phenoment iselective mating with the oddrare type Increases RS of rare type Humans use mating for cultural and social purposes not just for producing offspring What is a species Leopard Frogs Range from Maine to Florida Would mate with adjacent groups but when they are mixed regionally they do not produce fertile offspring Evolutionary Stable Strategy ESS John Smith Maynard The most successful reproductive strategy over the longrun in an environment Mating system that assures greatest relative reproductive success for the majority of players or individuals Sociobiology De nition the scienti c study that examines evolutionary explanations for social behaviors within species 1 Sel sh Strategy Species in which the players will never see eachother again non social species 2 Game Theory prisoner s dilemma inmate a and inmate b are both caught if they are both nice they will both bene t if one is mean and the other is nice one will bene t and one will lose if they are both mean to each other they will both lose Also referred to as reciprocal altruism Hypoxia Heat Cold Modern Life November 17 2009 Levels of Adaptation 1 Re ex 7 breathing pull away from fire eye blinking 2 Accommodation 7 a When first encountered a mild stress bothers you b Eventually stress is ignored 7 get used to it c Heat noise smells 3 Acclimatization 7 a Short term responses to stressors i Change in physiology ii Body adjusts ii Hours 7 days 7 weeks V Responses to hypoxia and cold b Long term responses to stressors i Same as short ii Increased blood ow and RBCs in hypoxic setting 4 Developmental Acclimatization 7 a During growth and development b Raised in stressful environment c Conception to completion of growth 5 Genetic adaptation 7 change in allele frequencies 6 Culture a Clothes re etc b Main Form of Adaptation way to adapt without a physiological change c Genetic adaptation is always our FINAL response Basal Metabolic Rate BMR Energy required to maintain basic physiological function while at rest BMR is the highest when you are young and growing BMR is higher in winter than in spring Body Proportions Physi010gy anatomy and body proportions are related to heat and cold tress B0dy proportions vary clinally in humans and animals in relation to environmental temperatures Bergmann s Rule B0dy mass increases with decreasing temperature thus reducing the surface to volume ratio and conserving heat 1 g 2 1 1 2 mm 1 mass a su acu ma 5 su aoe ma 2A nurlm Innmun s suvnca urnmu a lllusralnn maemmanns Rule from anuaamiy Allen s Rule Body extremities decrease With deceasing temperatures further reducing the surface to volume ratio and conserving heat From le to right 7 Heat loss increases Body Size and Environments ln cold environments animals have squat round bodies With short extremities ln warm environments animals have long cylindrical bodies With long extremities Even pygmies have this body form Surface area of the body increases as the square volume increases as the cube Sitting height ways to measure Eliminates le len Measures heatproducing body core Greater in cold environments short squat bodies have a shorter leg length more total body in torso Body measuremean of military recruits compared from the North and South Conf1rmed Bergmann s and Allen s rules Demonstrated developmental responses to environment rather than genetic Pigs in Minnesota Half liter outside in cold weather Other half inside warm Outside fatter and shorter legs lnside leaner and longer legs Pigs in cold more fat and bigger hams Ridding the Body ofHeat reducing core 1 Radiation a Give off body heat to another object in line of sight b Not touching c Bodies naturally radiate heat 2 Evaporation a Excess body heat converts to liquid sweat to gas b Releases latent heat of vaporization 3 Convection a Transfers heat to something moving b Air breeze or a fan or to moving water c Blood moves heat from region to region by convection 4 Conduction a Transfer heat to objects that are touching b Sitting against a cold wall c Heat moves from inside to outside body by conduction Sweat is the major means of human thermoregulation works poorly in a humid environment Can lose 2 liters of water per hour under hot conditions Humans insensitive to water and electrolyte loss Def1cit made up at night and during sleep Hydromeiosis 7 back pressure on sweat glands from sweat not evaporating from skin Stops your production of sweat Occurs in hothumid environment toColdu quotquot thecore l l Shivering a Muscle contractions generate heat 2 Goose Bumps a Contracting erector pili muscles of hair follicles b Constricting the skin c Retains heat 3 Lewis Waves a Reduce heat loss by convection Cultural a Without culture without shelter without fire etc humans not well accepted to living in cold environments 4 Thermal Stress Response 7 Heat 1 Detection a Cognitive Response b People lt 60 years old can detect a temperature change of 1 C c People gt70 years old can detect a temperature change of 23 7 25C 2 Peripheral dilation a Blood ows to capillaries at skin surface allowing heat exchange to environment 3 Cardiovascular activity a Increased heart activity delivers more bloodheat to extremities i Related to deaths of very young and old in hot weather 4 Sweat and evaporative cooling a Number of sweat glands varies from person to person and population to population b of sweat glands working at any time also varies c Heat adapted persons produce thinner sweat little water few electrolytes and have reduced heart rates d Thinner blood due to more liquid in blood Adaptations to Hot Environments Thin torsos long extremities larger surface to volume ratio Enhanced heat loss by radiation evaporation and convection Adaptations to Cold Environments Rounder torsos Shorter extremities Lower surface to volume ratio Vasoconstriction 7 decreased blood ow to extremities and skin Lewis Waves Increased BMR Higher amounts of brown fat 7 generates more heat Heat and Cold Adaptation Women not best subjects for heat stress studies Often anemic due to menstrual cycle Body temperatures uctuate during menstrual cycle Have higher heat conservation due to more body fat Natural Experiment Set of circumstances in natural environment that closely mimic controlled laboratory experiment Best in small groups with same cultural background Best with simple socioeconomic structure and technology Complex groups with modern technology alter the environment 7 difficult to interpret Ecological model for studying human variation Cannot ethically experiment on people or tell them who to breed with Find a group living with a stressor and compare them to a similar group without the stressor high altitude vs low altitude Find a stressor and try to determine how it affects variability in one population Natural Experiments Related to High Altitude Hypoxia l HAN7 High Altitude Natives sedantes haven t migrated vs HAN who have migrated to lowlands 2 LAN 7 Low Altitude Natives sedantes vs LAN migrants to the highlands 3 Nonnative Europeans who settled in both highlands and lowlands Other Natural Experiments 1 People who settled in a malarial environment a Sickle cell anemia and hemoglobin C disease 2 People in the New guinea highlands with and without Kuru a prion disease 3 People on Guam 50 die of ALS Lou Gering Disease a ALS related to high Al Cr and Mg diets b Heavy metals deposited in brain Vocabula Stressor anything that takes body out of homeostasis u Homeostasis maintenance of body at a dynamic equilibrium Attempt by the body to maintain a steady state via feedback mechanisms Hypoxia low oxygen content or availabilit Common at high altitudes high altitude gt8000 feet Before modern technology no way to alleviate hypoxia Leadville CO is the highest residential community in the US Allostasis and Allostatic Load Body s response to stressors promote physiological responses 7 allostasis Continual responses to stressors over time has somatic costs 9 allostatic load AL Allostasis body has different set points every minute hour month year examples range of pH compatible with life is narrow 7 range of body temperature broad People Living at High Altitudes 1 Rocky Mountains 7 Occupied since 30000 BP 2 Andes Mountains 7 Occupied since 30000 BP 3 Himalayan Mountains amp Tibetan Plateau 7 Occupied since 500000 BP 4 Ethiopian Highlands 7 Occupied since 800000 BP Stressors at High Altitude l Hypoxia 7 12 the partial pressure of oxygen at sea level Cold Poor nutrition base High UV radiation less atmosphere to block Dry environment Difficult terrain a Have to move up and down 9959 Adaptations to High Altitudes l Andes a Barrelshaped chest b Bigger lungs allow for greater oxygen uptake and saturation 2 Himalayas a Genetic adaptation mutation or founder s effect b RBCs have greater affinity of oxygen Responses to Hypoxia l Re exes a Increase in breathing rate b Decrease in activity rate c Slow down due to lack of oxygen 2 Short Term Acclimatization a Increased production of RBCs 7 increases hematocrit thick solids in blood b Increased ability to transport oxygen c Increased blood plasma 3 Long Term Acclimatization a Further increase in RBCs Increase in capillary system especially around muscles Increase in mitochondria in body cells especially muscle cells Young person increases ability to carry oxygen increases blood thickness Old person increased plasma thins the blood therefore under more stress i Thicker blood more susceptible to heart attack oaoc BarrelChest Both genetic and environmental causes 1 HAN born at high altitude with grandparents there have maximum barrelchest 2 HAN born at low altitude have less of a barrelchest 3 LAN born at low altitude with LAN grandparents have normal chest 4 LAN born at high altitude have a somewhat barrelchest environmental component 5 If born of European migrants at high altitude have a very slight barrelchest Genetic predisposition developmental acclimatization and environmental in uences Migration From Low to High Altitude Chronological age is inversely correlated with maximum ability to consume oxygen Aerobic capacity Total lung capacity Barrelchest increase with time and exposure to high altitude hypoxia The younger one arrives at a high altitude the better aerobic capacity they will develop Aerobic Capacity at High Altitudes 25 is due to developmental changes 25 is due to genetics 50 due to environment 46 months in advance Other Adaptations to Hypoxia A proxy for genetics is skin color differences at low and high altitudes In Nepal a genetic basis for RBCs carrying more oxygen Reduced in hematocrit 48 of blood is hematocrit in Nepal 30 to 35 here Whereas 522 hematocrit in the Andes Other Human Stressors 1 Nutrition 2 Temperature hot cold 3 Pollution 4 Environmental toxinsheavy metals 5 Radiation 6 Infectious genetic diseases 7 Other people 8 Culture Variation in Human Disease Patterns November 19 2009 Infectious Diseases Affected by Genes Environment Culture Va Across Groups of People SeX age socioeconomic status nutrition behaviors ethnicity geography climate genetics multifactorial interactions among causes Infectious Diseases Measles Fenner Culture change and population size Population of 300000 needed to maintain Provides 40005000 new casesyear Measles is a disease of modern civilization Viral infection 7 10 days 7 contagiousimmune Infectious Diseases Tuberculosis Airbome spores survive in environment Remain infectious for long periods Very young and old most susceptible Survive TB decades 7 large population not needed Infectious Diseases Worms Parasitic worms survive long without host symptoms Lymphatic filariasis Humans have genetic defenses 7 HLA haplotypes Enter body through oralfecal exposure Found in human corpolites May encapsulate in muscles as dormant cysts for decades Cyclical transmission from pigs to humans in some cultures Generation Def1ned as about 20 years today Length of time from a woman s birth to birth of her middle daughter Women determine generation length May have many children in their lifetime Men not aware of which children they sire Infectious Diseases today claimed 25 years ago 7 infectious diseases defeated by antibiotics 20 years ago 7multidrug resistant forms Venereal diseases Staphylococcal and streptococcal diseases MRSA HIV and ebola Viruses emerged from hot wet tropics PreViously likely controlled by local ecological relationships PreVious ecological relationships disrupted Began attacking humans as new host Fenner s Research Certain diseases need athreshold human population for maintenance DiVided cultures and populations into disease periods Each experienced a different spectrum of diseases Hunting and gathering 7 wormsbacterial Slash and burn agriculture 7 parasite Agriculture 7 dietary deficiencies Irrigated cities 7 infectious Viruses waterborne Industrial cities 7 human madepollution and wastes Introduction of sanitary reforms 7 chronic Measles needs 45000 cases per year to be endemic Hence idea population size for measles 300000 TB long term chronic airbome illness hence needs smaller population Typhoid also needs a small population Parasitic infections needs exposure to excrement occurred in settled population Missing Nutrients Vitamin A Beta carotene 7 arctic Vitamin D 7 dark crowded early industrial revolution 7 London Paris Vitamin C Scurvy 7 British Niacin corn niacin deficiency 7 pellagra Americas Folate spinal bifida Calcium osteoporosis Iron red meat Selenium rashes psoriasis comes from crops in high selenium soil linked to osteoporosis in African American women Stresses in modern world Traffic smoke air pollution Pace of life Water pollution Bovine growth hormones estrogen progesterone caffeine etc Leach into the water EG Male sh around some factories in London developed female coloring and internal organs Low sperm count in males today attributed to estrogen pollution in water Secular trends in humans Height Menarche Age appears to be decreasing in westemized populations from 1617 years to 11 12 years More proteinfat in diet More hormones in food Chronic adult degenerative diseases Senescence Epiphen0mena of reproduction After attaining maximal reproductive potential Characteristic of modern society Increasing organismal complexity immune and endocrine system culture etc senescence becomes an inherited property of system Reserve capacity of organs diminishes with age wear and tear and degeneration Reserve capacity used by the age of 50 determines length of life after 50 Aging Evolutionary model Ger0nt010gy scientific study of senescence and problems related to aging Senescence biological process leading to increased susceptibility to internal and external stresses leading to increased risk of death Ge139iat139ics medical field dealing with care of elders Ecological relationships Animal populations under stress seek new mates Lions and tigers mate produce ligers and tigons All baboon species seem capable of interbreeding Common and pygmy chimpanzees interbreed Population size and processes in Human evolution Mortality 7 people die 7 deaths Fertility 7 people are born 7 births Population change deaths 7 births New population pop deaths 7 births Rate of natural increase in population r births 7 deathspopulation r Life table 7 model of population based upon mortality rates by age Rate events population at risk for the event over a speci c time Ratio rate 1 rate 2 unitless Malthus An essay on the principles ofpopulation 1798 If unchecked increases at a geometric rate ie 2 4 8 16 whereas the food supply grows at an arithmetic rate Pt por t Malthus Predictions Subsistence severely limits population level When the means of subsistence increases population increases Population pressures stimulate increases in productivity Increases in productivity stimulate further population growth Since this productivity cannot keep up with the potential of population growth for long population requires strong checks to keep it in line with carryingcapacity Individual costbene t decisions regarding sex work and children determine the expansion or quot ofr r 39 quot and r J quot Checks will come into operation as population exceeds subsistence level The nature of these checks will have signi cant effect on the rest of the sociocultural system 7 Malthus points speci cally to misery vice and poverty Ecological fallacy assumes that because 2 variables covary across populations they are causally related Example Cardiovascular disease today cultural phenomena associated with low caloric intake during gestation due to world war and depression Example of intrauterine fetal programming Epidemiological transition 3 stages 1 High infectious mortality short life expectancy 2 Declining infectious mortality increasing life expectancies 3 High chronic disease mortality high life expectancy Demographic transition 7 3 stages 1 High mortality all ageshigh birth rates lots of kids 2 declining mortality at all ages declining birth rates still lots of kids 3 Low mortalitymost deaths after reproductive ageslow birth ratesstable populations Life Table systematic way of illustrating the demography of a population usually by age or sex based on current mortality in a population everything is equated to a population of 100000 original population is the cohort size radix Sociobiology 112409 The study of modern human variation and how genes affect behavior Nature vs nurture debate 7 cannot truly be separated environment beings in the womb EO Wilson systematic study of the biological basis of human social behavior Premise Social cultural systems came into being to improve enhance reproductive success of individuals in that system Basic idea is that social systems evolve because of ongoing interactions among and between individuals there is a biological basis for some aspects of social behavior Female choice malemale competition altruism etc I II I I 1 It is extreme to say that all 39 are 39 J by genes How do behaviors in uence evolution Behavior form of adaptation Behaviors may act as Reproductive Isolating mechanism between populationsspecies Behavior may alter the form of an organ 7 thereby directing its biological evolution easy to see in animals what about humans Humans do not mate randomly Culture often determines who is a desirable or permissible mate Culture system of learned behaviors that are shared among members of a group and passed on to the next generation by teaching Female choice Sexual selection Incest taboos Malemale competition Hidden estrus in females pregnant Infanticide Social Strategies acted on by NS Altruism behavior that lowers individual fitness but raises fitness of another andor overall fitness of a population Ultimate selfsacrifice for the team Lowers individual fitness iraises inclusiveness Not to be confused with parental investment PI Not group selection Selfishness Individual raises own tness at other s expense Raises tness of ego lowers tness of group Selects against others and not against ego Long Term NS might favor some altruism since it bene ts the greatest of people Reciprocal altruism tit for tat perform an altruistic act today expecting that to receive an altruistic act now or later Only strategy that does not allow cheaters evolutionary stable strategy ESS Applications widespread existence of purposeful behaviors in animal world indicates a link to NS Primates are highly social as are humans Altruism could be based on natural selection which focuses on competition Dif cult to imagine how it could give rise to an instinct that leas one organism to sacri ce itself for another Reciprocal altruism Cost to you bene t to someone else 9 bene t to you cost to someone else Sel shness bene t to you cost to someone else Spite Cost to you cost to someone else WC WynneEdwards suggested group selection however sociobiologists saw no empirical support Even when genuinely altruistic behavior occurs eg a warning cry could be individual selection anyone could be cheating nonreciprocal Kin Selection Favor relativeskin over others Related by descent Improve their tness since they carry genes identicalbydescent Individuals invest more in relatives than nonrelatives To the degree they are related to you bene t to siblingsinvesting in own genes maximize individual representation in next generation improve reproductive success cultural phenomenon e g cross cousin marriage parallel mating if wife dies marry her sister All of this leads to inclusive tness IF total contribution of genes through offspring and other relatives all of the alleles identical by descent passed on to next generation but devalued by own contribution to relative s total tness Hamilton de ned Total Fitness RS IF All alleles identical to you by descent that are passed on to the next generation Consanguinity biological term for mating with relatives Inbreeding offspring share alleles identicalby descent Incest a sociocultural term 7 de ned differently in different social settings Since people are usually in close contact with kin it pays to be altruistic and sel sh with them They are partially related to you Self interest arises when we are both sel sh and altruistic at the same time Studies of HYMENOPTERAN insects By EO Wilson in his book Sociobiology Males are haploid drones and all females worker or queen are diploid Queens being the only maternal contributor are equally related to both the drones and the workers the queen s best interest is to invest equally in both brother male and female offspring the workers have an interest in investing twice as much in sisters as brother sex ratio of Hymenoptera the queen produces 55 the workers selectively neglect the haploids ends up being more diploids in the next generation about 21 easy to show competition in insects humans are more complex nepotism in humans primate relatives have multimale consorting by females may be an attempt by females to confuse paternity prevent male infanticide of the infants primates tend to be matrilocalmatrilineal John Maynard Smith s Game Theory Sel sh acts 7 e g cuckoo birds cuckoo birds lay eggs in another s nest ends up raising the coocoo s offspring wo a cost to the offspring or parent ZeroSum game Also called prisoner s dilemma In real social situations the question is whether or not you will have to interact with the individual again in the future evolutionary stable strategy ESS strategy between individuals that over time results in the best outcome for majority of individuals ESS Most genetic success in the end will be titfortat always be altruistic until something bad happens then change strategy reciprocal altruism social relationship social systems could be in uenced and genetically based in biology best strategy of partnership Competition for scarce resources Different levels of investment that females and males put into the growth and development of offspring reproductive behavior is different so that each can maximize their genetic contribution to later generations rewards are different so behaviors are different E O Wilson female choice high energy in reproduction must make a careful choice about the most fit male chooses males best on quality Malemale competition low energy investment in growth and development of offspring invest in copulation to improve reproductive success quantity invest little in offspring bc do not really know own offspring Parental Investment Low in many mammalian offspring High in gibbons monkeys and humans absolutely essential for success Homosexuality Do not reproduce but may invest in people carrying their genes auntinguncling behavior societies with crosscousin mating males do not know that females offspring are related to them if sister then at least 1A related to them Evolution amp Human Variation in the Modern World December 1 2009 Infectious Disease Infectious Diseases Caused by pathogenic microorganisms Diseases can be spread directly or indirectly What type of information do infectious diseases tell a human biologist QQ Centu 7 Infectious diseases Sequence of childhood diseases Rubella German measles Birth Defects Childhood disease Rubeola measles MMR vaccinated against Contagious spread easily Contact with ENT of infected Scarlet fever Severe childhood disease Caused by a group of bacteria also causes strep Roseola Acute disease high fever rash Fifth disease Information Artic populations lack Vitamin A Industrial cities lack Vitamin D Oldtime sailors lacked Vitamin C Rice diet lacks thiamin Brown rice does contain thiamin Traditional huntergatherer societieshave not had endemics of measles or other infectious diseases What about now HlNl What else contributes to one s diet Liquid Why would liquid be an important component to one s diet Water essential nutrient consumed from exogenous sources to satisfy metabolic demand Humans may have first settled down in one place to brew beer connected to development of cereal agriculture Beer was an important food source why Contains grain proteins and vitamins Takes 4 months to brew beer Also takes time to ferment wine Metabolism Set of chemical reactions that occur in living organism to maintain life Metabolism Syndrome Combination of medical disorders Result increased risk of Cardiovascular Disease amp diabetes The Metabolic Syndrome Combines a number of agerelated factors into a syndrome obesity Insulin resistance Hyperinsulinemia atherosclerosis Metabolic dysregulation can result in Increases in Leptin and TNFalpha Hypertension Death can occur from Diabetes Myocardial infarcation Heart attack Body Habitus quot quot 39 somatic 139 r and J 39 that r J39 r to illnesses and chronic degenerative conditions CDCs Aspects of body shape size or proportion associated with diseaseearly mortality BMIbody mass index 7 poorly associated with fatness Adiposity and subcutaneous fat deposits Somatotypes Relative fat pattern indices Body Habitus Risllts for high BMI and obesity 9 common and varied Hyperinsulinemia and insulin mutations Hyperglycemia Hyperlipidemia leptin levels and mutations High calorie fat protein CHO diets Number of adipocytes Gene gene and geneenvironment interactions Metabolic efficiency Low calorieslow fat stores gt 85 high calories sufficient fat stores lt50 Cardiovascular Disease CVD Death from CVD increased after WW1 and WWII Now decreasing worldwide Every year of survival after age 20 7BP raises about 20 to 25 mmHg 40 year old has a 56 mmHg higher BP than a 20 year old in the US Mortality Trends in the US First two are infectious diseases IDs Reduced in modern settings last two are chronic degenerative diseases CDDs Increased in modern settings Diabetes is metabolic disease Today part of metabolic syndrome Mortality Transitions Total cancer mortality currently is rising Why Rate has not changed substantially Infectious disease mortality is decreasing CVD disease mortality is decreasing Public health measuresculture reduce deaths caused by IDs Atkins Diet low carbohydrates leads to ketosis Ketones 7 byproducts of fatty acid metabolism Low carbohydrates 7 ketones build up Increase risk of gall stones by 20 By following this diet one places themselves in a state of low ketoacidosis Maintaining the Soma Homeostasis Body s attempt to maintain a steady state within its metabolic milieu defined as a dynamic equilibrium older concept of setpoints and return to baseline Stressor Anything that pushes soma out of homeostasis can be environmental Allostasis Body s constant metabolic response to stressors that alters physiological set points Allostasis Physiological range of somatic responses Rather than set points body responds to environmental stressors with constant change Different set points advantageous at different times Sleepawake activenonactive Blood pressure mode 24hr pattern of highs and lows as environmental response Normal Allostatic Response Initiated by a stressor Sustained for an appropriate interval tumed off Allostatic Load can not halt all ill effects of stress on soma responses to stress may themselves harm soma may be detrimental to longterm health but promote short term survival cortisone stress response hormone damages cells measure of somatic stress high bp damages heart and arteries Evolutionary Pressures in Modern Settings Other people 7 war homicide political systems sociocultural systems Environment 7 pollution toxic chemicals radiation parasites infections Life Style 7 surfeit of calories fat protein exerciselack thereof smoking alcohol etc Heather Hampel Genetic Counseling HNPCC amp The American Founder Mutation October 27 2009 Health professionals with degrees and experience in medical genetics and counseling GCs provide supportive counseling to families serve as patient advocates and refer individuals and families to community or state support services GCs serve as educators and resource people for other health care professionals and for the general public Some counselors also work in administrative capacities Many engage in research activities related to the field of medical genetics and genetic counseling Breakdown of Primary Roles Clinical 83 Teaching Educational 54 Research 32 CoordinationAdministration 29 Careers in Clinical Genetic Prenatal 55 Cancer 39 Pediatrics 36 Adult noncancer 24 Specialty disease 14 Prenatal Patients Pregnant woman has a brother with cystic fibrosis CF and wants to know the chance that her baby will have CF too A pregnant woman with no family history of genetic conditions has just had an ultrasound that showed her baby has a birth defect Cancer Genetics Patients A 30 year old woman has a family history of breast cancer and wants to know her risk of also developing breast cancer A 22 year old man with thyroid cancer was recently diagnosed with Multiple Endocrine Neoplasia Type 2A He wants to know more about the condition and what it means for his future and his family Pediatric Patients A baby is born with multiple congenital anomalieslow birthweight heart defect and clubfeet among others and is referred to genetics for diagnosis A 2 year old child has been diagnosed with a metabolic disorder in the ICU after suffering an acute crisis Adult Patients A 35 year old woman whose mother had Huntington disease HD wants to know the chance that she will develop HD A 40 year old man has had high cholesterol since age 25 and a family history of early onset coronary artery disease ypical patient routine The basics Obtain detailed personal and family medical history ReView available medical records Propose differential diagnosis Discuss features of possible hereditary syndromes EXplain genetics of syndrome Discuss testing process and risks ys benefits Outline management options Follow up with letterreferrals etc Other careers for genetic 5 Research clinical epidemiological laboratory Education Politics Salary UniVersity medical center mean salary is 51111 Starting median salary in our region is 42500 Colorectal cancer Microsatellite Instability Pathway and Chromosome Instability pathway CIN is 85 Why determine which CRC cases are MSI and which have LS All MSI CRC patients have a better prognosis MSI CRC patients MAY need different treatment in future LS patients at high risks for second primary cancers CRC and others LS patients have at risk relatives who could benefit from genetic testing Autosomal Dominant50 chance that if you have lynch smdrome that you will pass it on MSI is caused by a failure of mismatch repair MMR genes What is the American Founder Deletion A large gene deletion causing HNPCC ldentif1ed in at least 22 distinct families who thru genetic studies have been shown to be distantly related Through geneaology three families have been linked to the Clapp family The American Found Mutation is formed from the Founder Effect Which is where new people travel to an island etc and start a family The genes from those two individuals are passed on and only those genes Genetic Polymorphisms and Health Anthro 301 October 29 2009 Midterm ZNovember 12th Lynch Syndrome could be a single mutation that happened in one person HLAMHC Responsible for self recognition and antibody defenses Human Leukocyte antigen systemmajor histocompatibility compleX HLA in humans MHC in other mammals Present foreign antigens to Tlymphocytes to stimulate an immune response HLA System 6p21 Responsible for histocompatibility Tissue rejection typing All cells in the body have tissue antigens Every cell is marked with HLA proteins D markers are not on every cell On leukocytes Codes for glycoproteins In mice HLA is spread out over the genome 1419 chromosomes most on number 17 Concentrated on chromosome 6 in humans D antigens mark white cells the helper T cells are modified to be immune competent Autoimmune diseases are associated with the HLA system All the D loci have a subset of loci within them with their own alleles Some have over 100 known alleles 9 highly polymorphic 6p21 inclues about 100 transcribed units plus a lot of psedo genes Linear sequence HLA system is inherited as a haplotype One haplotype comes from each parent 6 major HLA loci More loci in this 115 million bp segment of DNA than any other place in the human genome class I HLA genes are AB and C Self markers A B and C genes code for glycoproteins Found on all body cels except erythrocytes rbcells This is why blood transfusions are possible Class H HLA genes are DP DQz and DR At least 4 loci for each serotype Each of these 6 major loci has 50200 known alleles DP DQz DR genes code for glycoproteins that are on Blymphocytes and macrophages Present antigens to Tlymphocytes to generate antibody manufacture Group I A thru G except DP DQz and DR Histocompatibilty markers on all cells SELECTION AGAINST HOMOZYGOSITY Group 2 macrophages WBC s carry D markers needed to reject foreign tissues and organisms Minimum of 6 million indiVidual haplotypes perhaps 33 million for AG alone Number of combinations would be this number squared or 36 million haplotypes for the human populations 1 in 167 people would have one of the same haplotypes by random assortment But different haplotypes segregate in different populations Forensic Applications of HLA Paternity ldentif1cation of the dead DNA fingerprinting of criminals Evolutionary biology Applications of HLA Relatedness of individuals Bottlenecks in prehistory Population affinities Uniqueness of inbred groups Disease susceptibilities and longevity Viral inserts 8 of the human genome DNA from human endogenous retroviruses HERVs 1000s Oldest 550 MY ago during vertebrate evolution Most recent HERVK113 about 200000 years BP Viruses were defeated by survivors but some were integrated into genome Because they infected gametes and were passed on to future generations Most are in noncoding regions Many are used as templates within the HLA system retroviruses are not like measlesinfluenza mumps Evolutionary biology Some are remolded into active proteins HERVs may provide defenses against exogenous Retroviruses May occupy docking sites on receptors used by ERV HLA Alleles and Diseases HLA associations with autoimmune diseases B27 increases the risk of ankylosing spondylitis Bone disease causes bone to turn to mush Arthritis bowl diseases Most carriers of B27 mutation show no disease Dr3 increases risk of type I diabetes Pancreatic beta cells are attacked by antibodies Prior viral infection with sequence similarity to proteins on pancreatic cells Dw2 multiple sclerosis Apolipoproteins Four types ABCll E and more Short proteins about 300 amino acids long avg length Transport synthesis and breakdown of lipids Three major alleles for apolipoprotein E E2 E3 E4 chromosome 19 locus E2 low cholesterol E3 moderate cholesterol E4 high cholesterol 9 late onset Alzheimers Mediterranean allele very low cholesterol High density Lipoprotein HDL Mainly apolipoprotein A A1 A11 HDL Good cholesterol Carries bound cholesterol to liver to be metabolized Collected excess cholesterol from cellsvessel walls for return to liver and disposal Delivers cholesterol to gonads for steroid hormones lnhibits monocyte adhesion to vascular walls lnhibits thrombin induced binding of fibrinogen to platelets lnhibits formation of foam cells Low Density Lipoprotein LDL not the worst cholesterol but a bad one lnteracts with LDL receptors on the liver no innate system to dispose of excess cholesterol the environment of evolutionary adaptation the environment that hominids evolved in had a low cholesterol Mainly contains apo B and E E IS IMPORTANTSS LDL BAD CHOLESTEROL DUDES Very low density Lipoprotein LDL contains mainly apo CH also found in HDL LDL Acts similar to LDL except even more atherogenic Chilomicrons low density fats transported from intestines to liver for metabolism Apoliprotein E4 Has only 1 cystine no disulfide bond lnteracts poorly with liver LDL receptors Favors plaque formation and atherogenesis Binds poorly with microtubules in the brain Associated with late onset alzheimers ages 70 Apolipoprotein E table 0 E2 in Yanomami have low fat diets in Amazon and high apo E4 E4 associated with heart disease and strokes in modern settings In tradiational setting E4 an advantage maintinas higher LDL in blood in low dietary fat setting High fat intake in modern settings high body fat Apolipoprotein E EM found only in one village near Milan Italy Allele associated with low cholesterol and CAD in a high fat intake setting Low LDL bad cholesterol Apolipoproteins are involed in cell surface interactions Associated with neurotransmitters lnteract with brain cells May promote lateonset Alzheimers Mutant LDL receptor on liver does not interact with apo E early death and heart disease E4 decreased in centenarians E2 higher Long lived people tend to have more E2 than E4 Familial Hypercholesterolemia High cholesterol in the blood due to mutant LDL receptor Liver receptors do not recognize protein cholesterol is not eXtracted from blood Stored as lipid plaques in eyelids kneeds hands Simple trait intermediate heterozygote CO DOMINANT Homozygous dominant for the mutinent cholesterol 700 mgdl fatty blood Heterozygous 350 mgdl treatment for high cholesterol thru lifetime Wild type homozygote recessive normal 20 to 30 years old 240 gdl now 170 mg dl nerve sheaths are made out of cholesterol November 3 2009 Familial Hypercholesterolemia Homozygous Dominant cholesterol 700 mg fatty blood Heterozygous 350 mgdl treatment for high cholesterol through lifetime Wild type homozygote recessive normal 20 to 30 year old 240 gdl Now 170 mgdl Example South Africa High frequency mutant LDL receptor in some groups Boers Dutch colonizers religious enclaves branching pattern from coast to interior for specific churches founder effect two brothers were church leaders passed gene on to many descendents Plasmaphoresis Cleans fat out of blood l o of all people in US carry mutant LDL receptor 50 of people treated at lipid clinics carry mutants P53 the antioncogene gene Discovered when searching for oncogenes in mice 1970s 53 Kilodalton protein Oncogenes genetic loci that lead to cancer BRCA 1amp2 RAS usually house keeping loci P53 was never observed to cause cancer Reexamined in 1989 found to associated with tumor suppression P53 Transcription factor that controls cell cycle and thereby halts development of cancer lnitiates DNA repair and apoptosis halts cell cycle cancer initiation multihit model Apoptosis of cells exhibiting abnormal growth 9 normal p53 knocked out 9 cancer neoplasm development series of 300 cancer patients 320 mutant p53 observed About 50 of all lung colon and bladder carcinomas have mutations in p53 ournal of NIH Research and Science named p53 the molecule of the year in 1993 Tumor suppressor protein Guardian of the Genome 17p131 about 393 aa length cellular tumor antigen with 3 domains transcription activation dna binding homooligomerization eXtension of dna Specif1c mutations yield specific cancers aa 249 bladder cancer hot spot for mutation highly conserved molecule in its functional domains humans 17 rats 10 mice 11 Observed in most sexual reproducing species Wild type p53 halts cell division at the point of DNA replication Wild type maintained no cancer develops mutation cancer develops Marks cells for apoptosis by initiating transcription of DNA cistrons coding for other proteins Apoptosis nontraumatic cell death Nucleus dissolves cellular DNA is cut into pieces of about 700 base pairs Macrophages ingest the DNA chunks and cellular debris Short halflife 9 20 min Mutant forms longer halflives 9 greater than 20 min half lives vary for proteins collagen structural 9 lifetime digestive enzymes 9 30 mins Neurotransmitters 9 instantaneously or immediately LiFurmani Syndrome children born heterozygous for mutant p53 tumor suppression is reduced develop tumors in early adulthood or earlier p53 also mutates Within somatic cells Porphyria Vampire s Disease Mutation in enzymes needed for heme production porphyrins are the main precursors of heme characteristics skin with little to no color aVoid sun to avoid severe risk of skin cancer gums retreat iron deficient mental disorders Garlic stimulates production of hemoglobin but makes prophyria painful Drinking blood as remedy in middle ages MedieVal Transylvania nobles lived in castles Peasants did not constant sun eXposure any porphyria patients would die young Nobles were protected by being able to stay indoors and live longer Legend of Count Dracula Alcohol Dehydrogenase Enzymes secreted by stomach lining and liver that catalyze the oxidation of alcohol ethanol to acetaldehydes Two major phenotypes fast or slow codominant polymorphism Heterozygotes are intermediate US and Europe 6 are slowslow Asia 90 are slow slow Alcohol consumption anerse curvilinear association with CHD coronary heart disease risk Alcohol raises blood HDL Homozygotes for ADH3 allele slower alcohol metabolism greatest risk reduction Significant decrease in risk for CHD 1 drinksday Moderate consumption lowers CHD risk Xeroderma Pigmentosum Australia and South Africa highest frequencies Xeroderma Pigmentosum Genetic disorder of DNA repair in which the body s normal ability to fiX mutations caused by UV light is disabled Skin malignancies basaliomas skin cancers in endothelial cells Nucleotide excision repair enzymes are faulty Homeobox Genes A stretch of DNA that regulates development and determines the body plan in animals Plants have homeobox genes but different H0meobox genes are linearly arranged and sequentially turned on and off during development to make body parts Homeobox genes are inherited as a haplotype humans have 4 clusters chromosome 2 7 12 17 About 180 base pairs HOX cluster of genes determine the placements of segments of the body Sickle cell Anemia and Other hemoglobinopathis November 3 2009 Hemoglobin Hb Protein found in RBC contains Fe iron binds oxygen and transports to body tissues binds carbon dioxide for return to the lungs consists of 4 polypeptide chains 3 alpha 2 beta and 4 Fe molecules heme is the Fe molecules and the proteins Anemia low oxygen delivered to tissues abnormal Hb reduction in the RBC numbers Hb of 98 of human adults 2 alpa chains 141 amino acids long 2 beta chains 146 amino acids long different hemoglobins are made at different points in the human lifespan Fetal Hb 2 alphachains 2 gammachains 146 amino acids long Less than 1 of adults have fetal Hb Child Hb 2 alpha chains 2 deltachains 146 amino acids long Nearly 2 of adults have child hb In adults fetal Hb and child Hb do not transport oxygen as efficiency as adult Hb Alpha chain in Hb More highly conserved Presumably important in sustaining life 2 Loci 4 alleles code for the alpha chain Likely basis for all other chains Beta gamma and Delta chains 1 locus 2 alleles for each chain Arranged linearly on chromosome lnherited as a haplotype Slightly different base pair sequences likely arose by gene duplication followed by mutation Scattered along this haplotype are multiple pseudogenes short noncoding duplications Turned on off sequentially during normal development gamma chain gene turned on then off delta chain turned on then off f1nally beta chain gene is turned on Thalassemias Hereditary form of hemolytic anemia Reductions in Hb chain synthesis Alpha ad beta thalassemias Alphathalassemias too few achains betachain tetramers carry oxygen poorly common in malaria regions mediterraniean and Africa deletions but also have extensionsframe shift mutations over 80 known mutations Major both alleles at 1 or 2 loci deleted homozygous clinical symptoms Minor normal gene and a deleted gene at 1 or both loci heterozygous clinical symptoms may not be penetrant degree to which the genotype shows in the phenotype Betathalassemias too few beta chains tetramers of the alpha chains common in malaria areas of the Mediterranean most are point mutations nonsensedeletions duplications also about 150 mutations are known Thalassemias beta thalassemias often fetal type of anemia RBCs abnormally large macrocytic anemia low Hb content per cell Poor transport of oxygen facial and skull bones are thick Most mutations are not polymorphic ie occur at lt10o frequency Still have significant variation in Hb Coolers Anemia fetal thalassemia mutations that cause cooley s Anemia are polymorphic about 10 frequency seVere betathalassemia most thalassemia alleles are thought to be neutral or transitional neutral mutations may build at high frequencies in isolated inbreeding demes Associatinos with Malaria Sickle cell allele Glucose6phosphate dehydrogenase g6PD deficiency Xlinked Hemoglobin c allele thalassemias Sickle Cell Anemia First disease identified by electrophoresis Heterozygotes had 2 spots of betachain Hb Dominant and recessive homozygotes had only one Three genotypes SS normal prone to malaria Ss carrier anemia susceptible to malaria but not as bad as SS fair poor altitude hypoxia ss sickle cell disease die from ss disease before reproducing Sickle Cell Hb Substitution mutation at the 6th amino acid in the betachain Glu glutamic acid no charge 9 yal valine charge Hemoglobin C Disease Substitution mutation at the 6th amino acid in the betachain Glu 9 Lys lysine charge causes a milder form of anemia than sickle cell trait S and C hemoglobins Both make RBC sickle reduce their ability to carry oxygen Reduce K potassium content in RBC malarial parasite reproduces less efficiently reducing malaria load on body Malarial Parasites Different parasites all protozoans Transmitted by different species of mosquitoes Different Hb variants are more effective against different kinds of malarial parasites Plasmodium falciparum most common malaria in the world Annual death toll 69 million people does not kill immediately years to decades long term survival that becomes more and more debilitative multiple opportunities for transmission 80 of modern human infections 7 90 deaths Plasmodium vivaX most frequent and Widely distributed in the past both Hbs and Hbc protect against both P falciparum and P vivaX malaria Duf blood group Null allele Fyquot Monomorphic in Plasmodium vivaX areas RBC lacks Duffy antigens attack sites for Plasmodium vivaX duffy null allele not found in Europeans 100 in W Africa and malarial environments Frequency of Fy85 in African Americans 15 admixture with Europeans Fact Heterozygote carrying both an allele for sickle cell anemia and an allele for hemoglobin C disease has a better fitness than a heterzygote for either alone Ecology of MalariaCarrying Fly between 47 feet altitude Common by bodies of still water most active at dawn dusk Cultural protections away from water live on a hill house on stilts work in midday or at night SS individuals High malaria parasite load parasite is reproducing rapidly in them Die younger and more frequently from malaria More debilitation from chills fever and sweats have decreased energywork capacity copulate less frequently Malaria fever increased miscarriages kills sperm lrregular ovulationmenstrual cycling Fewer people live to adulthood to help in child rearing Ss Low parasite loads parasite is reproducing more slowly die older and less frequently from malaria because of less debilitation from chills fever and sweats more work capacity copulate more frequently Decreased malaria fever fewer miscarriages higher sperm counts more regular ovulation Ss Least afflicted by malaria shortest lifespan f1tness is 0 selection is 1 Do not surive to reproduce Sickle cell mutation probably occurred multiple times before malaria environment No selective pressure no increase in frequency mutations do not respond to environment Vocabulary Isoproteins Different forms of the same protein in different individuals eg isoenzymes Zoonosis disease that has gone from being in animals to being in humans malaria hiv avian flu swine flu chicken pox Vector transmits from one host to another mosquitoes for malaria Pandemic everyone is eXposed because the disease is so prevalent in a particular geographical area eg malaria in subSaharan Africa Epidemic disease comes in a wave infects all susceptible people then leaves eg in uenza Episodic Disease occurs in episodes over time eg black plague Ecology of Malaria Pre6000 BPE November 5 2009 Malaysian Agricultural Complex was being practiced in SE Asia Swidden agriculture of root crops and pulses Yams taro cassava sorgum and millet Africa lush rain forests many animals People were huntergatherers with very low population densities mainly lived in scattered groups along waterways Ecology of Malaria 6000 BPE Millet cultivation appeared in Africa Forests were cleared for planting Stagnant pools of water accumulated in cleared fields Human population density increased Settlements became larger and more stable Mosquitoes new host By 5000 4000 BP malaria was widespread among people in Africa Sickle cell and hemoglobin C mutants advantaged in now malarial areas lncreased in frequency of these alleles due to protection against malaria FavismG6Pd Deficiency glucose6phosphate dehydrogenase on pathway of glucose metabolisms G6PD is X Linked def1ciency in G6PD RBCs carry less oxygen Malarial parasites need oxygen potassium and phosphate G6PD deficiency protects against malaria Favism found in malarial areas of the Mediterranean especially common in Sardinia and Sicily Mutation Founder Effect People with favism react negatively to quinine A drug for treating malaria People with favism aren t able to metabolize fava beans Staple in the Mediterranean diet Hemolytic crisis when beans are eaten RBCs stop carrying oxygen aggregate and being dying Malaria Major selective agent for Sickle cell anemia probably the oldest mutation Hemoglobin C disease seems to be replacing sickle cell anemia now alphathalassemia and betathalassemia favism G6PD deficiency Strongest Facts Sickle RBCs will aggregate around a cholesterol plaque in blood vessels Under crisis capillaries and arterioles will rupture Hypoxic conditions will cause a crisis Sickle Cell Anemia Pleiotropic Effects 1 Destruction of sickled RBC leading to anemia 2 RBC clumping and interference with circulation 3 Collection of RBC in spleen with subsequent spleen enlargement Sickle Cell Anemia It was known that blacks were prone to be carriers of sickle cell anemia so they were prohibited from ying airplanes during WWI but did late in WWII Feared they would undergo a hemolytic crisis at altitude The success of the Tuskegee airmen during WWII changed this attitude Inbom Errors of Metabolism IEM November 5 2009 IEM inborn errors of metabolism genetic variability in how we metabolize our environment Mutations that change the structure and or function of enzymes Form of human variation IEM Enzyme mutants isozymes present form birth Alter biochemistry of metabolism lsoenzymes differ in their primary structure in amino acid sequence Metabolism sum of how enzymes convert environment to self and maintain soma body environment anything that comes into your body Amylases Nonspecif1c enzymes digest a variety of carbohydrates CHOs 1p21 inactivated by gastric acid of stomach Secreted in saliva begins CHO digestion Saliva acts as a disinfectant because it contains amylase and other molecules antibodies enzymes Amylase also digests sugars on microbes spit may clean hands better than water Multiple amylase isoenzymes in humans General function of enzymes Majority of mutations likely neutral Mutant broad specificity enzymes little effect on phenotype Function can be assumed by another enzyme Digestive enzymes broad specificities Biosynthetic pathway enzymes tend toward narrow specificities Enzymes Most enzymes producing inborn errors of metabolism are highly substrate specific Two categories of enzymes 1 Anabolic build things up 2 Catabolic Breaks things down IEMs 1 missing or defective enzymes most common cannot process substrate within body eg PKU 2 Loss of degradative pathway Cannot get rid of substrate eg Tay Sachs disease sphingolipids build up 3 Errors of absorption or reabsorption eg cystinuria build up of cystine 4 Coenzyme defects mutation prevents enzyme compleX from forming a Coenzymes vitamins metals proteins b Must attach to a polypeptide chain to make active enzymes IEM alter metabolic pathways Avoid IEM s by 1 Alternative pathway Amylase use alternative enzyme or take longer 2 Rid body of substrate Excrete 3 Detoxify Render substrate benign or reduce toxicity 4 Find alternative source for a product you need Generally rare Most lethal prior to birth Effect may show several metabolic steps beyond the enzyme defect Alternative metabolic pathway IEM may not be seen Most IEMs are recessive traits Heterozygotes often show incomplete penetrance NQWrbpVN Usually primary errors of DNA Symptoms may not be directly related to error No Phenylalanine PKU buildup of phenylpyruvic acid PKA 8 IEM Strong selection against parents Large range of variation PKU Incomplete penetrance pp 50mg Phe100ml plasma high amount of Phe Pp 10mg Phe100ml plasma incomplete penetrance of recessive allele PP 1mg Phe100ml plasma normal amount of Phe in blood Heterozygote 12 phenylalanine hydroxylase activity intermediate phenotype Redundtant system 2 normal alleles not needed Enzyme activity of PP genotype is more than needed Heterozygote has adequate enzyme Pleiotropic Effects CNS neurons die in infantschildren Mental retardation and low IQ Motor system abnormalities Depressed melanin formation light skin and hair Deposit phenylpyruvic acid into joints mimicking arthritis PKU Phe and phenylpyruvic acid build up in blood Phe filtered by kidney Phe reabsorbed build up of toxic metabolite Rare autosomal recessive disease 110000 people What is the frequency of the recessive allele of the dominant allele of the heterozygote frequency PKU QAZ 110000 0001 requency of recessive genotype pp and recessive phenotype Qsqure root 0001 PKU in Celtic Populations Frequency in 2510000 Recessive allele freq 05 Heterozygote frequency 095 May be heterozygous advantage in Celtsl No detrimental effects in heterozygotes lighter skin solar radiation More Phe in blood less converted to Tyr not making as much melanin In northern latitudes lighter skin Allows for greater vitamin D synthesis by UV PKU allele entrenched in Celts mutation of founder s effect Northern latitudes Vitamin D increases absorption of calcium and decreases rickets in children In all states but two newborns are screened for PKU now only Arkansas Test accurate and those affected are easily treated Federal subsidy for Phe free diet Albinism Melanin is not properly formed Varieties of albinism different loci Different sizes shapes and darkness of melanin Sexual selection for albinism among the Hopi Indians Culturally yalued phenotype Albinism Loci Three different loci cause albinism 1 TyrosinasenegatiVe lack of tyrosinase Tyr not formed into melanin 2 TyrosinasepositiVe tyrosinase is present so the biochemical block is somewhere else Make Tyr from phenylalaine but no melanin 3 ocular albinism only in the eyes eyes are pink Albinos are blue eyed and see poorly at night blue eyed see well at dawn and dusk Brown eyed see well at night and poorly at dawn and dusk If the genotype of 1 ttAA and the genotype of 2 TTaa Two albinos could give rise to a normal child Per se is not fatal Albinos prone to melanomas skin does not block UV radiation Albinism allele frequency 01 Melanin is on phenylalanine metabolic pathway Same pathway as epinephrine and norepinephrine associated with fight or flight adrenaline Tyrosine Tyrosinosis build up of tyrosine Tyrosine on pathway to 1 Melanin 2 Thyroxin 3 Epinephrine and noepinephrine Neurotransmitters involved in stress responses Too much of these substances damages neurons Cretinism lodine de ciency goiter enlarged thyroid lnsufficient iodine and thyroid enlarges in attempt to make more thyroxin Pleiotropic traits 1 Stunted growth 2 Deficiency of bone mineralization 3 Mental retardation 1 Iodine or thyroxin prevents cretinism Occurs in high frequency in the New Guinea highlands Alkaptonuria Not a serious disease in youth OXidation of homogentisic acid in urine black pee disease ocranosis Defect in homogentisate 1 2dioxygenase Builds up and is excreted in urine turns black upon eXposure to the oxygen Excess homogentisic acid accumulates in joints particularly fingers and toes causing painful arthritis Urine is sterile unless one has UTI Urinary tract infection Used to disinfect wounds for centuries Confederate women saved urine and processed it into potassium nitrate for the war effort Tay Sachs Disease Hexosaminidase A deficiency GMZ gangliosidosis Chromosome 15 HEXA gene exon 11 mutation 1278insTATC Gangliosides are fatty acid derivatives sphingolipids active in signal transmission Hexosamindase A aids in recycling of sphingolipids Nervce cells of brain Block neurotransmission generation of nerves cells eventually burst Tay Sachs Disease Mental retardation neurons become distended Developmental reversion loss of motor function blindness cherryred spots on retina symptoms begin around 1 year after birth Death occurs by age 5 tay Sachs alleles in all population 1300 particularly high in Ashkenazi Jews 127 130 160 came to us in 1880s 1950 from Poland and Russia Ashkenazi Jews 1 in 3600 are homozygous recessive Cajuns 130 160 q Irish Am 150 q Heterozygote advantage Ghettos of Europe High incidence of tuberculosis and typhoid fever Concentrated populations lnfectious disease easily transmitted 1910 Philadelphia rabbi began keeping mating records of his congregation would not approve marriages between families among tay sachs family members Practice spread to synagogues along east coast Today Tay Sachs nearly eliminated from American Jewish population All descendents of Ashkenazi Jews in US are tested for hexosaminidase A deficiency Orthodox Jewish Dor Yeshorim anonymous screening program Evolutionary Biology Both PKU and tay Sachs reduce parental fitness Nine months maternal investment in utero Up to 5 years Parental Investment P1 in baby Heterozygote advantage Finishing past lecture November 10 2009 Mucopolysaccharaidosis Glycosaminoglycans Glocosaminoglycans are long chains of CHOs Found in joint uids Help in forming bone cartilage Lysosomal storage disease Autosomal recessive disease affecting collagen Collagen most common protein in body 25 Currently 28 named forms Mucopolysaccharidosis Mucopolysaccharides associate with collagen are not brown down in lysosomes One of 11 lysosomal enzymes dysfunctional Mucopolysaccharides build up in sells progressive cellular damage bone muscle nerve cells 9 death Cystinuria Autosomal recessive disease only aa with sulfur 1st metabolic disease studied scientifically Due to inadequate reabsorption after kidney filtration Cystine becomes excessively concentrated in urine bonds with itself preciptates out of solution as crystals forms kidney stones painful in kidney bladder and ureters other aa do not crystallize 1 10000 very rare compared to normal kidney stones Gout Autosomal recessive disease of purine and uric acid metabolism Ben Franklin Henry VIII Isaac Newton Sodium urate uric acid crystals accumulate in the joints and tendons inflammatory reaction causes painful metabolic arthritis deposits increase in size and burst through skin as sinuses Exude chalky White material we don t make vitamin c 1st disease of excess identified Egyptian mummies and Roman Gladiators Purine generator is stuck on will not respond to feedback inhibition Purine includes DNA bases adanine and guanine excess purines are metabolized to uric acid Enzyme glutamine PRPP amino acid transferase overactive Makes excess purines metabolized to uric acid Coenzyme defect Symptom of diabetes and metabolic syndrome Blood flows more slowly at eXtremities particularly at big toe most common symptom is pain in big toe m Humans and guinea pigs cannot make vitamin c scurvy before citrus fruits on sailing ships Uric acid replaces vitamin C metabolically Overuse of vitamin C gt uric acid Genetics and Ancestry Identifying susceptibility to Diseases November 10 2009 Race biologically subgroup in a species that is genetically more different than others Phenotype vs Genotype m is based on socially defined phenotypic classification Skin color morphological features cranial social classes Ancestry is based on a genetic classification Haplotypes YChromosome mtDNA Ancestry Information Markers AIM Race has been defined as Demes local breeding populations Geog139aphical Race Large population groups occupying entire continents AfricanAfrican American Darkskinned individuals Encompasses a broad genetic heterogeneous cluster of thousands of populations genetic miXture from Europeans is 25 White Lightskinned individuals Typically of European origin Millions of people spread throughout the world Heterogeneous group who possess certain points of the genetic array dispersed throughout Europe Does race define an individual s genome ie genetic makeup Skin color is dispersed according to ultraviolet radiation by latitude Example of Socially De ned Phenotypic Classifications Skin Color Melanin blood keratin bilirubin Factors that determine skin color Amount of melanin and keratin Closeness to surface of blood vessels Skin thickness Number size color and shape of melanin granules prod by melanosomes Spectrophotometer used to measure blue red and amber light reflected by the skin the curves for European light and African dark will not overlap there is a dip in the curve at 550nm for light skinned individuals because they absorb blue light Four diallelic and codominant loci equivalents determine skin color Probably hundreds of loci that cause small effects on skin color 70 o of skin color is due to genes 30 is due to environment Skin color is not a marker for continent of origin nor is it useful in determination of disease susceptibility Skin color does however define a class that fits our preconceived images of inequality Socially defined phenotypic classifications ie race cannot be used to defineidentify the genetic traits an individual or a population possess Anthropology and human biology also reinforces this concept Biological race does not EXiSt but social race does eXist What is ancestry Genetic based description of an individual s or population s ancestral background Constructed through studying the genomes that compose a population Documents the genetic diversity of individuals Within a population therefore document the genome for a population Geographic ancestry Commonality of alleles and frequencies shared by peoples of the same area Crews and Gerber 2008 Genetic mechanisms leave their signatures on the DNA of populations and descendents by introducing local allelic variants and unique populationspecific genes Why is Ancestry Important Biomedical studies Racial typing has occurred within the field of biomedical research Hypertension diabetes cardiovascular disease Suggestion is that documenting the ancestry of individuals will provide an adequate platform for determining disease risk as well as treatment Biodiversity in Human Populations Sequence variation exists within and between populations 95 of human genetic variability is within populations 5 of human genetic variability is between populations Results from a broad sharing of genes throughout the human gene pool Example Southern African tribes differ at specific loci eg HLA systems just as they differ from equivalentsized groups living over 2000 miles to the northwest A lack of concordance of trait distribution Genetic variation is not randomly distributed Clinal distribution A distribution of frequencies that show a systematic gradation over space different groups express varying degrees of a trait genetic differences between groups are in the process of breaking down Migration and intergroup mating lndividuals are likely to have ancestry that is a mixture of different groups Allele Frequencies provide the genetic markers that distinguish between populations Small fractions of SNP differ among the world s continental population groups Older alleles more common across many populations ancestral alleles Newer alleles exhibit a low frequency and are localized derived alleles Haplotypes Over several generations segments of ancestral chromosomes in an interbreeding population are shuf ed through repeated recombination events Some segments occur as regions of DNA sequences that are shared by multiple individuals There are regions that are not broken up by recombination and are separated by places where recombination has occurred These are the haplotypes WA population of subproups exhibiting different allele frequencies Example European males mating with indigenous women Example FY null allele of the Duffy blood type in WestAfrican populations USrepresents a melting pot How far back does your family tree go in the US Think about the amount of genetic varation that came into the US when migration occurred Genetic blender Sociopolitical history of the US Slavery and segregation 7 increasedecrease How does knowing the geographical ancestry of an indivudla and or population in uence biomedical research and clinical applications for treating disease Haplotypes The use of haplotypes can identify populations that are at high risk for a particular disease HLA haplotypes and diabetes Jewish women and breast cancer Tay sachs and east coast Hasidic Jews Y chromosome Blood groups Human variation can be highly signi cant in the determination of disease susceptibility and treatment thereafter in terms of understanding how human variation is patterned and what it means variations re ect race but patterns and processes of human evolution interaction wit the environment and population movements
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'