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Download Chapter 14. Mendel & Genetics
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Mendel & Genetics Gregor Mendel • Modern genetics began in the mid-1800s in an abbey garden, where a monk named Gregor Mendel documented inheritance in peas – used experimental method – used quantitative analysis • collected data & counted them – excellent example of scientific method Mendel’s work • Bred pea plants – cross-pollinated true breeding parents (P) – raised seed & then observed traits (F1) • filial – allowed offspring to cross-pollinate & observed next generation (F2) Mendel collected data for 7 pea traits Looking closer at Mendel’s work P true-breeding true-breeding X purple-flower peas white-flower peas F1 100% purple-flower peas generation (hybrids) 100% self-pollinate F2 generation 75% 25% purple-flower peas white-flower peas 3:1 What did Mendel’s findings mean? • Traits come in alternative versions – purple vs. white flower color – alleles • different alleles vary in the sequence of nucleotides at the specific locus of a gene purple-flower allele & white-flower allele are 2 DNA variations at flower-color locus different versions of gene on homologous chromosomes Traits are inherited as discrete units • For each characteristic, an organism inherits 2 alleles, 1 from each parent – diploid organism • inherits 2 sets of chromosomes, 1 from each parent • homologous chromosomes • like having 2 editions of encyclopedia – Encyclopedia Britannica – Encyclopedia Americana What did Mendel’s findings mean? • Some traits mask others – purple & white flower colors are separate traits that do not blend • purple x white ≠ light purple • purple masked white – dominant allele • fully expressed – recessive allele • no noticeable effect • the gene makes a non-functional protein Genotype vs. phenotype • difference between how an organism “looks” & its genetics – phenotype • description of an organism’s trait – genotype • description of an organism’s genetic makeup Explain Mendel’s results using …dominant & recessive …phenotype & gentotype P F1 Making crosses • using representative letters – flower color alleles P or p – true-breeding purple-flower peas PP – true-breeding white-flower peas pp PP x pp Pp Looking closer at Mendel’s work P true-breeding true-breeding X purple-flower peas white-flower peas PP pp 100% purple-flower peas F1 generation (hybrids) phenotype 100% Pp Pp Pp Pp self-pollinate F2 generation 75% 25% purple-flower peas white-flower peas ? ? ? ? 3:1 Punnett squares Pp x Pp male / sperm P p % genotype PP % phenotype 25% 75% Pp female / eggs 50% P p PP Pp Pp pp Pp pp 25% 25% 1:2:1 3:1 Genotypes • Homozygous = same alleles = PP, pp • Heterozygous = different alleles = Pp homozygous dominant homozygous recessive Phenotype vs. genotype • 2 organisms can have the same phenotype but have different genotypes purple PP homozygous dominant purple Pp heterozygous Dominant phenotypes • It is not possible to determine the genotype of an organism with a dominant phenotype by looking at it. PP? Pp? Test cross • Cross-breed the dominant phenotype — unknown genotype — with a homozygous recessive (pp) to determine the identity of the unknown allele x is it PP or Pp? pp Test cross x x PP P pp p p Pp Pp Pp p P 100% P Pp Pp p pp p Pp Pp 50%:50% 1:1 pp pp Mendel’s laws of heredity (#1) P • Law of segregation PP – when gametes are produced during meiosis, homologous chromosomes separate from each other pp – each allele for a trait is packaged into a separate gamete P p p P Pp p Law of Segregation • What meiotic event creates the law of segregation? Meiosis 1 Monohybrid cross • Some of Mendel’s experiments followed the inheritance of single characters – flower color – seed color – monohybrid crosses Dihybrid cross • Other of Mendel’s experiments followed the inheritance of 2 different characters – seed color and seed shape – dihybrid crosses Dihybrid cross P true-breeding yellow, round peas Y = yellow R = round generation (hybrids) F2 generation x YYRR yyrr y = green r = wrinkled yellow, round peas F1 self-pollinate true-breeding green, wrinkled peas 100% YyRr 9/16 yellow round peas 3/16 green round peas 3/16 1/16 yellow green wrinkled wrinkled peas peas 9:3:3:1 What’s going on here? • How are the alleles on different chromosomes handed out? – together or separately? YyRr YR yr YyRr YR Yr yR yr Dihybrid cross YyRr x YyRr YR Yr yR yr YR YYRR YYRr YyRR YyRr Yr YyRr Yyrr yR YyRR YyRr yyRR yyRr yr YYRr YyRr YYrr Yyrr yyRr yyrr 9/16 yellow round 3/16 green round 3/16 yellow wrinkled 1/16 green wrinkled Mendel’s laws of heredity (#2) • Law of independent assortment – each pair of alleles segregates into gametes independently • 4 classes of gametes are produced in equal amounts – YR, Yr, yR, yr • only true for genes on separate chromosomes YyRr Yr Yr yR yR YR YR yr yr Law of Independent Assortment • What meiotic event creates the law of independent assortment? Meiosis 1 The chromosomal basis of Mendel’s laws… Trace the genetic events through meiosis, gamete formation & fertilization to offspring Review: Mendel’s laws of heredity • Law of segregation – monohybrid cross • single trait – each allele segregates into separate gametes • established by Meiosis 1 • Law of independent assortment – dihybrid (or more) cross • 2 or more traits – each pair of alleles for genes on separate chromosomes segregates into gametes independently • established by Meiosis 1 Mendel chose peas wisely • Pea plants are good for genetic research – available in many varieties with distinct heritable features with different variations • flower color, seed color, seed shape, etc. – Mendel had strict control over which plants mated with which • each pea plant has male & female structures • pea plants can self-fertilize • Mendel could also cross-pollinate plants: moving pollen from one plant to another Mendel chose peas luckily • Pea plants are good for genetic research – relatively simple genetically • most characters are controlled by a single gene • each gene has only 2 alleles, one of which is completely dominant over the other Any Questions?? Probability & Genetics Genetics & Probability • Mendel’s laws: – segregation – independent assortment reflect same laws of probability that apply to tossing coins or rolling dice Probability & genetics • Calculating probability of making a specific gamete is just like calculating the probability in flipping a coin – probability of tossing heads? 50% – probability making a P gamete… P 50% Pp p PP P 100% P Probability & genetics • Outcome of 1 toss has no impact on the outcome of the next toss – probability of tossing heads each time? 50% – probability making a P gamete each time? 50% P Pp p Calculating probability Pp x Pp male / sperm P p sperm egg offspring P P PP P p 1/2 x 1/2 = female / eggs 1/2 x 1/2 = P PP Pp p Pp pp Pp 1/4 P 1/2 x 1/2 = p 1/4 1/4 1/2 p p 1/2 x 1/2 = pp 1/4 Rule of multiplication • Chance that 2 or more independent events will occur together – probability that 2 coins tossed at the same time will land heads up 1/2 x 1/2 = 1/4 – probability of Pp x Pp pp 1/2 x 1/2 = 1/4 Calculating dihybrid probability • Rule of multiplication also applies to dihybrid crosses – heterozygous parents — YyRr – probability of producing yyrr? • probability of producing y gamete = 1/2 • probability of producing r gamete = 1/2 • probability of producing yr gamete = 1/2 x 1/2 = 1/4 • probability of producing a yyrr offspring = 1/4 x 1/4 = 1/16 Rule of addition • Chance that an event can occur 2 or more different ways – sum of the separate probabilities – probability of Pp x Pp Pp sperm egg offspring P p Pp 1/2 x 1/2 = p P 1/2 x 1/2 = 1/4 Pp 1/4 1/4 + 1/4 1/2 Chi-square test • Test to see if your data supports your hypothesis • Compare “observed” vs. “expected” data – is variance from expected due to “random chance”? – is there another factor influencing data? • null hypothesis • degrees of freedom • statistical significance Any Questions?? Beyond Mendel’s Laws of Inheritance Extending Mendelian genetics • Mendel worked with a simple system – peas are genetically simple – most traits are controlled by a single gene – each gene has only 2 alleles, 1 of which is completely dominant to the other • The relationship between genotype & phenotype is rarely that simple Incomplete dominance • Heterozygotes show an intermediate phenotype – RR = red flowers – R’R’ = white flowers – RR’ = pink flowers • make 50% less color Incomplete dominance P X true-breeding red flowers true-breeding white flowers 100% pink flowers F1 100% generation (hybrids) self-pollinate 25% red F2 generation 50% pink 25% white 1:2:1 Incomplete dominance CRCW x CRCW female / eggs male / sperm CR CW CR CW CRCR CRCW % genotype CRCR CRCW % phenotype 25% 25% 50% 50% CRCW CRC W C WC W C WC W 25% 25% 1:2:1 1:2:1 Co-dominance • 2 alleles affect the phenotype in separate, distinguishable ways – ABO blood groups – 3 alleles • I A, I B, i • both IA & IB are dominant to i allele • IA & IB alleles are co-dominant to each other – determines presences of oligosaccharides on the surface of red blood cells Blood type genotype phenotype __ type B type B oligosaccharides on surface of RBC __ type AB both type A & type B oligosaccharides on surface of RBC universal recipient type O no oligosaccharides on surface of RBC universal donor IA i type A IB IB IB IA IB ii status type A oligosaccharides on surface of RBC IA IA i phenotype 1901 | 1930 Blood compatibility • Matching compatible blood groups – critical for blood transfusions • A person produces antibodies against oligosaccharides in foreign blood – wrong blood type • donor’s blood has A or B oligosaccharide that is foreign to recipient • antibodies in recipient’s blood bind to foreign molecules • cause donated blood cells to clump together • can kill the recipient Karl Landsteiner (1868-1943) Blood donation Pleiotropy • Most genes are pleiotropic – one gene affects more than one phenotypic character • wide-ranging effects due to a single gene: • dwarfism (achondroplasia) • gigantism (acromegaly) Acromegaly: André the Giant Pleiotropy • It is not surprising that a gene can affect a number of organism’s characteristics – consider the intricate molecular & cellular interactions responsible for an organism’s development • cystic fibrosis – mucus build up in many organs • sickle cell anemia – sickling of blood cells Epistasis • One gene masks another – coat color in mice = 2 genes • pigment (C) or no pigment (c) • more pigment (black=B) or less (brown=b) • cc = albino, no matter B allele • 9:3:3:1 becomes 9:3:4 Epistasis in Labrador retrievers • 2 genes: E & B – pigment (E) or no pigment (e) – how dark pigment will be: black (B) to brown (b) Polygenic inheritance • Some phenotypes determined by additive effects of 2 or more genes on a single character – phenotypes on a continuum – human traits • • • • • • skin color height weight eye color intelligence behaviors Albinism albino Africans Johnny & Edgar Winter Nature vs. nurture • Phenotype is controlled by both environment & genes Human skin color is influenced by both genetics & environmental conditions Coat color in arctic fox influenced by heat sensitive alleles Color of Hydrangea flowers is influenced by soil pH It all started with a fly… • Chromosome theory of inheritance – experimental evidence from improved microscopy & animal breeding led us to a better understanding of chromosomes & genes beyond Mendel • Drosophila studies A. H. Sturtevant in the Drosophila stockroom at Columbia University 1910 | 1933 Thomas Hunt Morgan • embryologist at Columbia University – 1st to associate a specific gene with a specific chromosome – Drosophila breeding • • • • prolific 2 week generations 4 pairs of chromosomes XX=female, XY=male Morgan’s first mutant… • Wild type fly = red eyes • Morgan discovered a mutant white-eyed male – traced the gene for eye color to a specific chromosome Discovery of sex linkage red eye female x white eye male all red eye offspring 75% red eye female x 25% white eye male How is this possible? Sex-linked trait! Sex-linked traits • Although differences between women & men are many, the chromosomal basis of sex is rather simple • In humans & other mammals, there are 2 sex chromosomes: X & Y – 2 X chromosomes develops as a female: XX • redundancy – an X & Y chromosome develops as a male: XY • no redundancy Sex chromosomes autosomal chromosomes sex chromosomes Genes on sex chromosomes • Y chromosome – SRY: sex-determining region • master regulator for maleness • turns on genes for production of male hormones – pleiotropy! • X chromosome – other traits beyond sex determination • hemophilia • Duchenne muscular dystrophy • color-blind Human X chromosome • Sex-linked – usually X-linked – more than 60 diseases traced to genes on X chromosome Map of Human Y chromosome? • < 30 genes on Y chromosome SRY Sex-linked traits H Xh x X HY HH XHh sex-linked recessive XH female / eggs male / sperm XH XH Y XH XH XH Y XH Xh Xh XH Xh XH Xh XhY XHY Y Sex-linked traits summary • X-linked – follow the X chromosomes – males get their X from their mother – trait is never passed from father to son • Y-linked – very few traits – only 26 genes – trait is only passed from father to son – females cannot inherit trait X-inactivation • Female mammals inherit two X chromosomes – one X becomes inactivated during embryonic development • condenses into compact object = Barr body X-inactivation & tortoise shell cat • 2 different cell lines in cat Male pattern baldness • Sex influenced trait – autosomal trait influenced by sex hormones • age effect as well: onset after 30 years old – dominant in males & recessive in females • B_ = bald in males; bb = bald in females Mechanisms of inheritance • What causes the differences in alleles of a trait? – yellow vs. green color – smooth vs. wrinkled seeds – dark vs. light skin – Tay sachs disease vs. no disease – Sickle cell anemia vs. no disease Mechanisms of inheritance • What causes dominance vs. recessive? – genes code for polypeptides – polypeptides are processed into proteins – proteins function as… • enzymes • structural proteins • hormones How does dominance work: enzyme = allele coding for = allele coding for functional enzyme non-functional enzyme = 50% functional enzyme • sufficient enzyme present • normal trait is exhibited • NORMAL trait is DOMINANT carrier = 100% non-functional enzyme • normal trait is not exhibited aa = 100% functional enzyme • normal trait is exhibited AA Aa How does dominance work: structure = allele coding for = allele coding for functional structural protein non-functional structural protein = 50% functional structure • 50% proteins malformed • normal trait is not exhibited • MUTANT trait is DOMINANT Aa = 100% non-functional structure • normal trait is not exhibited AA = 100% functional structure • normal trait is exhibited aa Prevalence of dominance • Because an allele is dominant does not mean… – it is better – it is more common Polydactyly: dominant allele Polydactyly individuals are born with extra fingers or toes dominant to the recessive allele for 5 digits recessive allele far more common than dominant 399 individuals out of 400 have only 5 digits most people are homozygous recessive (aa) Hound Dog Taylor Any Questions?? Studying Inheritance in Humans Pedigree analysis • Pedigree analysis reveals Mendelian patterns in human inheritance – data mapped on a family tree = male = female = male w/ trait = female w/ trait Genetic counseling • Pedigree can help us understand the past & predict the future • Thousands of genetic disorders are inherited as simple recessive traits – benign conditions to deadly diseases – albinism – cystic fibrosis – Tay sachs – sickle cell anemia – PKU Genetic testing Recessive diseases • The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all – Heterozygotes (Aa) • carriers • have a normal phenotype because one “normal” allele produces enough of the required protein Heterozygote crosses • Heterozygotes as carriers of recessive alleles Aa x Aa female / eggs male / sperm A A a AA AA Aa Aa A Aa a A a Aa Aa aa Aa a Cystic fibrosis • Primarily whites of European descent – strikes 1 in 2500 births • 1 in 25 whites is a carrier (Aa) normal lung tissue – normal allele codes for a membrane protein that transports Cl- across cell membrane • defective or absent channels cause high extracellular levels of Cl• thicker & stickier mucus coats around cells • mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections – without treatment children die before 5; with treatment can live past their late 20s Normal Lungs Clairway Na+ cells lining lungs mucus secreting glands Chloride channel Transports chloride through protein channel out of cell. Osmotic effects: H2O follows Cl- damaged lung tissue Cystic fibrosis Clairway Na+ cells lining lungs thickened mucus hard to secrete bacteria & mucus build up Tay-Sachs • Primarily Jews of eastern European (Ashkenazi) descent & Cajuns – strikes 1 in 3600 births • 100 times greater than incidence among non-Jews or Mediterranean (Sephardic) Jews – non-functional enzyme fails to breakdown lipids in brain cells • symptoms begin few months after birth • seizures, blindness & degeneration of motor & mental performance • child dies before 5yo Sickle cell anemia • Primarily Africans – strikes 1 out of 400 African Americans – caused by substitution of a single amino acid in hemoglobin – when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods • deforms red blood cells into sickle shape • sickling creates pleiotropic effects = cascade of other symptoms Sickle cell anemia • Substitution of one amino acid in polypeptide chain Sickle cell phenotype • 2 alleles are codominant – both normal & abnormal hemoglobins are synthesized in heterozygote (Aa) – carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stress • exercise Heterozygote advantage • Sickle cell frequency – high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes • 1 out of 400 African Americans • Suggests some selective advantage of being heterozygous – sickle cell: resistance to malaria? – cystic fibrosis: resistance to cholera? Heterozygote advantage • Malaria – single-celled eukaryote parasite spends part of its life cycle in red blood cells • In tropical Africa, where malaria is common: – homozygous normal individuals die of malaria – homozygous recessive individuals die of sickle cell anemia – heterozygote carriers are relatively free of both • High frequency of sickle cell allele in African Americans is vestige of African roots•••••• Malaria Prevalence of Malaria Prevalence of Sickle Cell Anemia Genetics & culture • Why do all cultures have a taboo against incest? – laws or taboos forbidding marriages between close relatives are fairly universal • Fairly unlikely that 2 carriers of same rare harmful recessive allele will meet & mate – but matings between close relatives increase risk • consanguineous matings – individuals who share a recent common ancestor are more likely to carry same recessive alleles A hidden disease reveals itself Aa x Aa male / sperm male / sperm A A A a A AA AA A AA Aa a Aa Aa a Aa aa female / eggs female / eggs AA x Aa Any Questions??