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 • usedquantitative analysis • collected data & counted them • Most traits in most species do not follow the simple Mendelian pattern, but it was a starting point
Mendel’s work Pollen transferred from white flower to stigma of purple flower • Bred pea plants • cross-pollinate true breeding parents (P) • P = parental • raised seed & then observed traits (F1) • F = filial • allowed offspring to self-pollinate& observed next generation (F2) P anthers removed all purple flowers result F1 self-pollinate F2
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 (locus = location on a chromosome) of a gene • some difference in sequence of A, T, C, G purple-flower allele & white-flower allele are two DNA variations at flower-color locus different versions of gene at same location 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 - same genetic loci (i.e. same genes), different alleles at those loci
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 • purplemaskedwhite • dominant allele • functional protein • masks other alleles • recessive allele • allele typically makes a malfunctioning protein mutantallele producingmalfunctioningprotein wild typeallele producingfunctional protein homologouschromosomes
X P purple white F1 all purple Genotype vs. phenotype • Difference between how an organism “looks” & its genetics • phenotype • description of an organism’s trait • the “physical,” the result of gene expression • genotype • description of an organism’s genetic makeup • Its combo of alleles, like “Pp”
Dominant ≠ most common allele • Because an allele is dominant does not mean… • it is more common, healthier, stronger, better, more likely, etc. Polydactyly dominant allele, yet rare!
PP pp x X P purple white F1 all purple Making crosses • Can represent alleles as letters • flower color alleles P or p • true-breeding purple-flower peas genotype PP • true-breeding white-flower peas genotype pp • In research, alleles are usually letter/number/symbol combinations (like ser83psE) Pp
Discussion Which of these are phenotypes and which are genotypes? 1. Curly hair 2. Jj 3. PE1PE2 4. Arthritic knees 5. Type B blood 6. Spotted fur and a pink nose 7. HHGg 8. Purple leaves and spiny stem
Punnett Square reminders • The side and top boxes = parents’ potential gametes, each equally likely. • Inner boxes = potential zygotes. • Punnett Squares predict the odds of each offspring being born with a given genotype/phenotype. • Does not ensure that, say, 50% of the children will definitely be freckled.
Genotypes • Homozygous = same alleles = PP, pp • “True-breeding” = homozygous • Heterozygous = different alleles = Pp • “Carrier” homozygousdominant heterozygous homozygousrecessive
x Test cross • Method to determine genotype in case of dominant phenotype • Breed the dominant phenotype with a homozygous recessive (pp) to determine the identity of the unknown allele How does that work? is itPP or Pp? pp
Discussion Suppose that the Y allele codes for orange fins and the y allele codes for yellow fins. The heterozygous genotype: __ The homozygous dominant genotype: __ The homozygous recessive genotype: __ A fish with yellow fins must have a _____________ genotype. A fish with orange fins could be either _____________ or ___________________. If a fish has orange fins, test-crossing it with a ______-finned fish will produce either 100% _____ or 50% orange/50% yellow. If the former result, the orange fish was _________. If the latter result, the orange fish was _________.
P P P p PP Pp pp p p Mendel’s 1st law of heredity • Law of segregation • during meiosis, alleles segregate • homologous chromosomes separate • each allele for a trait is packaged into a separate gamete • You only give 1 allele per gene to your child
Law of Segregation Suppose there’s an eye color locus, with the alleles B for brown eyes or b for blue eyes. A man has the genotype Bb, which gives him the phenotype brown eyes. Meiosis produces his gametes… b He can make gametes that are EITHER B or b. Half of his gametes will be one, half will be the other. That’s segregation! b b S Phase b b b b Meiosis I B Meiosis II B B B Normal cell in G1 B B B Four Gametes
Discussion Monohybrid cross practice! Show Punnett Squares to support your answer. • If two black bees (bees A and B) have 676 babies, all black; two red bees (bees C and D) have 983 babies, all red; and a different two black bees (bees E and F) have 524 babies, 220 red and 304 black, what was each bee’s genotype? Use any letter for the alleles that you want. • What generation were bees A,B,C,D,E, and F a part of? What generation were their children a part of?
Dihybrid cross • Other of Mendel’s experiments followed the inheritance of 2 different characters • seed color andseed shape • dihybrid crosses Mendelwas working outmany of the genetic rules!
F1 generation (hybrids) yellow, round peas 100% F2 generation Dihybrid cross P true-breeding yellow, round peas true-breeding green, wrinkled peas x YYRR yyrr Y = yellow R = round y = green r = wrinkled YyRr self-pollinate 9:3:3:1 9/16 yellow round peas 3/16 green round peas 3/16 yellow wrinkled peas 1/16 green wrinkled peas
9/16 yellow round YyRr YyRr 3/16 green round YR YR yr YR yR Yr yr Yr 3/16 yellow wrinkled yR 1/16 green wrinkled yr or Dihybrid cross YyRr x YyRr YR Yr yR yr YYRR YYRr YyRR YyRr YYRr YYrr YyRr Yyrr YyRR YyRr yyRR yyRr YyRr Yyrr yyRr yyrr
yellow green round wrinkled Mendel’s 2nd law of heredity • Law of independent assortment • different loci (genes) separate into gametes independently • non-homologous chromosomes align independently • classes of gametes produced in equal amounts • YR = Yr = yR = yr YyRr Yr Yr yR yR YR YR yr yr 1 : 1 : 1 : 1
Discussion • Complete a Punnett Square for this dihybrid cross problem! • If A = tall and a = short, while B = fuzzy and b = smooth… • What are the odds that a parent heterozygous for both traits and a short smooth parent will have a tall and fuzzy offspring?
Law of Independent Assortment EXCEPTION • If genes are on same chromosome & close together • will usually be inherited together • rarely crossover separately • “linked”
Rules of Probability • Probability scale ranges from 0 to 1 • Rule of Multiplication:determine the chance that two or more independent events will occur together in some specific combination. • Compute the probability of each independent event. • Then, multiply the individual probabilities to obtain the overall probability of these events occurring together. • Rule of Addition: probability of an event that can occur two or more different ways is the sum of the separate probabilities of those ways.
Rules of Probability • For instance, if I roll a six-sided die, what are the odds I’ll get a number that is equal to or less than 2? Which law did you use? • If I roll two dice, what are the odds I’ll get a 1 both times? Which law did you use?
Discussion • You have been using both rules all along! • How does the rule of multiplication come into play in a monohybrid cross? • The rule of addition?
Rules of Probability • What are the odds that a homozygous red-haired, heterozygous green-eyed, white-chinned cat (AAEeww) and a dark-haired, heterozygous green-eyed, white-chinned cat (aaEeww) would have a kitten with the genotype AaEeww? • We can solve each gene as a separate monohybrid problem, then multiply!
Discussion • AAEeww x aaEeww = ?% AaEeww
Discussion • Determine the probability of finding two recessive phenotypes for at least two of three traits resulting from a trihybrid cross between pea plants that are PpYyRr and Ppyyrr. • There are five possible genotypes that fulfill this condition: ppyyRr, ppYyrr, Ppyyrr, PPyyrr, and ppyyrr. • Hint: Use the rule of multiplication to calculate the probability for each of these genotypes, and then use the rule of addition to pool the five probabilities.
Answer: • The probability of producing a ppyyRr offspring: • The probability of producing pp = 1/2 x 1/2 = 1/4. • The probability of producing yy = 1/2 x 1 = 1/2. • The probability of producing Rr = 1/2 x 1 = 1/2. • Therefore, the probability of all three being present (ppyyRr) in one offspring is 1/4 x 1/2 x 1/2 = 1/16. • For ppYyrr: 1/4 x 1/2 x 1/2 = 1/16. • For Ppyyrr: 1/2 x 1/2 x 1/2 = 2/16 • For PPyyrr: 1/4 x 1/2 x 1/2 = 1/16 • For ppyyrr: 1/4 x 1/2 x 1/2 = 1/16 • Therefore, the chance of at least two recessive traits is 6/16 = 3/8.
Mendel chose peas luckily • Relatively simple genetically • most characters are controlled by a single gene with each gene having only 2 alleles • one completely dominant over the other • All the genes he chose happened to be on different chromosomes - whew!
Extending Mendelian genetics • The inheritance of traits can rarely be explained by simple Mendelian genetics • Various patterns of inheritance: incomplete dominance, codominance, pleiotropy, lethality, epistasis, polygenetic traits, multiallelic genes, sex-linked traits… • Not all traits just determined by nuclear DNA: environmental effects, gene regulation, mitochondrial DNA…
Incomplete dominance • Heterozygote shows a NOVEL, intermediate, blended phenotype • example: • RR = red flowers • rr = white flowers • Rr = pink flowers • make 50% less color RR WW RW RR RW WW
100% pink flowers F1 generation (hybrids) 100% 25% red 50% pink 25% white 1:2:1 F2 generation Incomplete dominance X true-breeding red flowers true-breeding white flowers P self-pollinate
Co-dominance • 2 alleles affect the phenotype equally & separately • Phenotype is not blended, it’s both of the true-breeding phenotypes simultaneously • Speckled chickens, Roan cows, human ABO blood groups • 3 alleles • IA, IB, i • IA & IB alleles are co-dominant • glycoprotein antigens on RBC • IAIB = both antigens are produced • i allele recessive to both
Pleiotropy • Most genes are pleiotropic • one gene affects more than one trait • dwarfism (achondroplasia)
Lethal pleiotropy Aa x aa Aa x Aa dominantinheritance a a A a Aa Aa AA Aa A A achondroplastic achondroplastic achondroplastic lethal a a aa aa Aa aa typical achondroplastic typical typical 50% affected:50% typical or1:1 67% affected:33%typicalor2:1
Discussion • What if an allele is lethal recessive? • Suppose that in a plant, the recessive allele for yellow seeds is lethal, the dominant allele for green seeds is not. • What phenotypic ratios would you get from a cross of… • GG x Gg? • Gg x Gg? • Gg x gg? (gg produced by genetically engineering gametes while leaving the somatic cells intact)
Epistasis • One gene completely masks another gene • coat color in mice = 2 separate genes • C,c:pigment (C) or no pigment (c) • B,b:more pigment (black=B) or less (brown=b) • cc = albino, no matter B allele • 9:3:3:1 becomes 9:3:4 B_C_ B_C_ bbC_ bbC_ _ _cc _ _cc How would you know thatdifference wasn’t random chance? Chi-square test!
Epistasis in Labrador retrievers • 2 genes: (E,e) & (B,b) • pigment (E) or no pigment (e) • pigment concentration: black (B) to brown(b) eebb eeB– E–bb E–B–
Polygenic inheritance • Some traits determined by additive effects of 2 or more genes • phenotypes on a continuum • human traits • skin color • height • weight • intelligence • behaviors
albinism Skin color: Albinism • However, albinism can be inherited as a single gene trait • aa = albino enzyme melanin tyrosine
Sex linked traits • Genes are on sex chromosomes • as opposed to autosomal chromosomes • first discovered by T.H. Morgan’s “Fly Lab” at Columbia U. • Drosophila breeding • good genetic subject • prolific • 2 week generations • 4 pairs of chromosomes • XX=female, XY=male
Classes of chromosomes autosomalchromosomes sexchromosomes
Discovery of sex linkage true-breeding red-eye female true-breeding white-eye male X P Huh!Sex matters?! 100% red eye offspring F1 generation (hybrids) 100% red-eye female 50% red-eye male 50% white eye male F2 generation
Let’s reconsider Morgan’s flies… P x x F1 XRXR XrY XRXr XRY F2 Xr Y XR Y XR XR XRXr XRY XRXR XRY BINGO! F1 XR Xr XRXr XRY XRXr XrY 100% red females 50% red males; 50% white males 100% red eyes
Genes on sex chromosomes • Y chromosome • few genes other than SRY • sex-determining region • master regulator for maleness • turns on genes for production of male hormones • many effects = pleiotropy! • X chromosome • other genes/traits beyond sex determination • mutations: • hemophilia • Duchenne muscular dystrophy • color-blindness
Ichthyosis, X-linked Placental steroid sulfatase deficiency Kallmann syndrome Chondrodysplasia punctata, X-linked recessive Hypophosphatemia Aicardi syndrome Hypomagnesemia, X-linked Ocular albinism Retinoschisis Duchenne muscular dystrophy Becker muscular dystrophy Chronic granulomatous disease Retinitis pigmentosa-3 Adrenal hypoplasia Glycerol kinase deficiency Norrie disease Retinitis pigmentosa-2 Ornithine transcarbamylase deficiency Incontinentia pigmenti Wiskott-Aldrich syndrome Menkes syndrome Androgen insensitivity Sideroblastic anemia Aarskog-Scott syndrome PGK deficiency hemolytic anemia Charcot-Marie-Tooth neuropathy Choroideremia Cleft palate, X-linked Spastic paraplegia, X-linked, uncomplicated Deafness with stapes fixation Anhidrotic ectodermal dysplasia Agammaglobulinemia Kennedy disease PRPS-related gout Lowe syndrome Pelizaeus-Merzbacher disease Alport syndrome Fabry disease Lesch-Nyhan syndrome HPRT-related gout Immunodeficiency, X-linked, with hyper IgM Lymphoproliferative syndrome Hunter syndrome Hemophilia B Hemophilia A G6PD deficiency: favism Drug-sensitive anemia Chronic hemolytic anemia Manic-depressive illness, X-linked Colorblindness, (several forms) Dyskeratosis congenita TKCR syndrome Adrenoleukodystrophy Adrenomyeloneuropathy Emery-Dreifuss muscular dystrophy Diabetes insipidus, renal Myotubular myopathy, X-linked Albinism-deafness syndrome Fragile-X syndrome Human X chromosome • Sex-linked • usually means“X-linked” • more than 60 diseases traced to genes on X chromosome