2 Inheritance Parents and offspring often share observable traits. Grandparents and grandchildren may share traits not seen in parents.Why do traits disappear in one generation and reappear in another?Why do we still keep talking about Mendel and his peas?
3 Darwin Prior to MendelScientists looked for rules to explain continuous variation.The “blending” hypothesis: genetic material from the two parents blends togetherHead size, height, longevity – all continuous variations - support the blending hypothesisThe “particulate” hypothesis: parents pass on discrete heritable units (genes)Mendel’s experiments suggested that inherited traits were discrete and constant
4 Why did Mendel succeed in seeing something that nobody else saw?He countedChose a good systemChose true-breeding charactersGregor Mendel
5 The field of genetics started with a single paper!
6 Mendel is as important as Darwin in 19th century science Mendel did experiments and analyzed the results mathematically. His research required him to identify variables, isolate their effects, measure these variables painstakingly and then subject the data to mathematical analysis.He was influenced by his study of physics and having an interest in meteorology. His mathematical and statistical approach was also favored by plant breeders at the time.
7 Mendel used an Experimental, Quantitative Approach Advantages of pea plants for genetic study:There are many varieties with distinct heritable features, or characters (such as color); character variations are called traitsMating of plants can be controlledEach pea plant has sperm-producing organs (stamens) and egg-producing organs (carpels)Cross-pollination (fertilization between different plants) can be achieved by dusting one plant with pollen from another
8 Self-fertilization Cross-pollination Easy to cultivate and a short life cycle- easy to control pollination- keep unwanted pollen out- cross-fertilize artificiallyhad discontinuous characteristicsflower colorseed textureMendel knew of at least 34Self-fertilizationCross-pollination
9 Mendel Planned Experiments Carefully Mendel chose to track only those characters that varied in an “either-or” mannerHe also used varieties that were “true-breeding” (plants that produce offspring of the same variety when they self-pollinate)He spent 2 years getting “true” breeding plants to studyAt least three of his traits were available in seed catalogs of the day
10 Mendel studied true breeding pea traits with two distinct forms
11 Terminology of Breeding P1 (parental) - pure breeding strainF1 (filial) – offspring from a parental crossThey are also referred to as hybrids – because they are the offspring of two 2 pure-breeding parentsF2 - produced by self-fertilizing the F1 plants
12 Phenotype Genotype PP (homozygous Purple 1 Pp (heterozygous 3 Purple 2 Because of the different effects of dominant and recessive alleles, an organism’s traits do not always reveal its genetic compositionTherefore, we distinguish between an organism’s phenotype, or physical appearance, and its genotype, or genetic makeupIn flower color in pea plants, plants have the same phenotype (purple), but different genotypes (PP and Pp)pp(homozygous1White1Ratio 3:1Ratio 1:2:1
14 The TestcrossHow can we tell the genotype of an individual with the dominant phenotype?This individual must have one dominant allele, but could be either homozygous dominant or heterozygousThe answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individualIf any offspring display the recessive phenotype, the mystery parent must be heterozygous
15 Mendel’s ModelMendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspringFour related concepts make up this modelThese concepts can be related to what we now know about genes and chromosomes
16 The First ConceptAlternative versions of genes account for variations in inherited charactersFor example, the gene for flower color in pea plants exists in two versions, one for purple flowers and the other for white flowersThese alternative versions of a gene are now called allelesEach gene resides at a specific locus on a specific chromosome
17 Allele for purple color Homologouspair ofchromosomesLocus for flower color geneAllele for white color
18 The Second ConceptFor each character, an organism inherits two alleles, one from each parentMendel made this deduction without knowing about the role of chromosomesThe two alleles at a locus on a chromosome may be identical, as in the true-breeding plants of Mendel’s P generationAlternatively, the two alleles at a locus may differ, as in the F1 hybrids
19 The Third ConceptIf the two alleles at a locus differ, then one (the dominant allele) determines the organism’s appearance, and the other (the recessive allele) has no noticeable effect on appearanceIn the flower-color example, the F1 plants had purple flowers because the allele for that trait is dominant
20 The Fourth Concept Known as “the law of segregation” Two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametesThus, an egg or a sperm gets only one of the two alleles that are present in the somatic cells of an organismThis segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis
21 Mendel’s Laws Explain his Data Mendel’s segregation model accounts for the 3:1 ratio he observed in the F2 generation of his numerous crossesThe possible combinations of sperm and egg can be shown using a Punnett square, a diagram for predicting the results of a genetic cross between individuals of known genetic makeupA capital letter represents a dominant allele, and a lowercase letter represents a recessive allele
22 Two types of “states” Homozygous: Heterozygous: an individual or a locus carries identical alleles of a given gene.Heterozygous:an individual or a locus carries different alleles of a given gene
23 Mendel’s Law of Segregation Members of a gene pairs (alleles) separate from each other during gamete formation.The underlying mechanism is separation and then segregation of homologous chromosomes during meiosis.Key terms:dominant and recessive traitsgenotype versus phenotype
24 Garrod, 1902 - human traits followed Mendelian rules Inborn errors of metabolismHint: much more common in first cousin marriages
25 LE 14-7Dominant phenotype,unknown genotype:PP or Pp?Recessive phenotype,known genotype:ppIf PP,then all offspringpurple:If Pp,then 1 2 offspring purpleand 1 2 offspring white:ppppPPPpPpPpPpPPPpPppppp
26 Mendel’s Second Law: The Law of Independent Assortment Mendel derived the law of segregation by following a single characterThe F1 offspring produced in this cross were all heterozygous for that one characterA cross between such heterozygotes is called a monohybrid cross
27 Mendel identified his second law of inheritance by following two characters at the same time Crossing two, true-breeding parents differing in two characters produces dihybrids in the F1 generation, heterozygous for both charactersA dihybrid cross, a cross between F1 dihybrids, can determine whether two characters are transmitted to offspring as a package or independently
28 LE 14-8 P Generation YYRR yyrr Gametes YR yr YyRr F1 Generation Hypothesis ofdependentassortmentHypothesis ofindependentassortmentSperm1YR1YryRyrSperm441414Eggs1YRyr2121YREggs4YYRRYYRrYyRRYyRr1YRF2 Generation(predictedoffspring)2YYRRYyRr1Yr4YYRrYYrrYyRrYyrr1yr2YyRryyrr1yR4YyRRYyRryyRRyyRr34141yr4Phenotypic ratio 3:1YyRrYyrryyRryyrr916316316316Phenotypic ratio 9:3:3:1
29 The law of independent assortment states that each pair of alleles segregates independently of other pairs of alleles during gamete formationStrictly speaking, this law applies only to genes on different, nonhomologous chromosomesGenes located near each other on the same chromosome tend to be inherited together
30 Probability Ranges from 0 to 1 Probabilities of all possible events must add up to 1Rule of multiplication: The probability that independent events will occur simultaneously is the product of their individual probabilities.Rule of addition: The probability of an event that can occur in two or more independent ways is the sum of the different ways.
31 Probability: The likelihood that an event will occur No chance of event probability = 0 (e.g. chance of rolling 8 on a six-sided die)Event always occurs probability = 1(chance of rolling 1,2,3,4,5,or 6 on a six-sided die)The probabilities of all the possible events add up to 1.# on dieprobability11/623456The probability of an event= # of chance of eventtotal possible events
32 Independent EventsThe probability of independent events is calculated by multiplying the probability of each event.In two rolls of a die, the chance of rolling the number 3 twice:Probability of rolling 3 with the first die = 1/6Probability of rolling 3 with the second die = 1/6Probability of rolling 3 twice = 1/6 x 1/6 or 1/36
33 Independent eventsWhat is the chance of an offspring having the homozygous recessive genotype when both parents are doubly heterozygous?
35 Dependent Events The probability of dependent events is calculated by adding the probability of each event.In one roll of a die, what is the probability of rolling eitherthe number 5 or an even number?Probability of rolling the number = 1/6Probability of rolling an even number = 3/6Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6
36 Dependent Events Parents are heterozygous for a trait, R. What is the chance that their child carries at least one dominant R allele?Probability of child carrying RR = 1/4Probability of child carrying Rr = 1/2Probability of child carrying R = 1/4 + 1/2 = 3/4
37 Multiplication and Addition Rules Applied to Monohybrid Crosses The multiplication rule states that the probability that two or more independent events will occur together is the product of their individual probabilitiesProbability in an F1 monohybrid cross can be determined using the multiplication ruleSegregation in a heterozygous plant is like flipping a coin: Each gamete has a 1/2 chance of carrying the dominant allele and a 1/2 chance of carrying the recessive allele
38 ½ chance of P and ½ chance of p allele results in ¼ chance of each homozygous genotype. There are two ways to get the heterozygous genotype so it is¼ + ¼ = ½Three genotypes give the same phenotype.
39 Solving Complex Genetics Problems with the Rules of Probability We can apply the rules of multiplication and addition to predict the outcome of crosses involving multiple charactersA dihybrid or other multicharacter cross is equivalent to two or more independent monohybrid crosses occurring simultaneouslyIn calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied together
40 YYRR yyrr Female Gametes YyRr ¼ ¼ ¼ ¼ YyRr YR Yr yR yr ¼ YR Yr yR yr ¼ ¼ ¼ ¼YyRrYR Yr yR yrYRYryRyrYYRRYYRrYyRRYyRrYyRrMale gametesYYrRYYrrYyRrYyrr9/16YyRRYyRryyRRyyRr3/163/16YyRrYyrryyRryyrr1/16
41 For a dihybrid cross – the chance that 2 independent events occur together is the product of their chances of occurring separately.The chance of yellow (YY or Yy) seeds= 3/4 (the dominant trait)The chance of round (RR or Rr) seeds = 3/4 (the dominant trait)The chance of green (yy) seeds= 1/4 (the recessive trait)The chance of wrinkled (rr) seeds= 1/4 (the recessive trait)Therefore:The chance of yellow and round= 3/4 x 3/4 = 9/16The chance of yellow and wrinkled= 3/4 x 1/4 = 3/16The chance of green and round= 1/4 x 3/4 = 3/16The chance of green and wrinkled= 1/4 x 1/4 = 1/16
42 So, Rr genotype = (1/2 x 1/2) x 2 = 1/2 RR genotype is (1/2 x 1/2) = ¼ Add these to get the combined probability.Can use to solve more complicated problems:AaBBccDdEeFFGghhIiJJKk x aaBbCCDdEEffggHhIIjjKk
49 Statistical AnalysisSimple cross: purple x whiteF1: all purpleF2: 2850 purple, 1150 white10x as many, butsame ratioUse Χ2 test to determine likelihood of getting this result by chanceΧ2 = total of (observed-expected)2/expected over all classes"Expected" is from null hypothesis - data fit a 3:1 ratio( )2/ ( )2/1000 = 30!P is <<less than 5%, so data are significantly different from null hypothesis
50 Inheritance patterns are often more complex than predicted by Mendel The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studiedMany heritable characters are not determined by only one gene with two allelesHowever, the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance
51 Extending Mendelian Genetics for a Single Gene Inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations:When alleles are not completely dominant or recessiveWhen a gene produces multiple phenotypesWhen a gene has more than two allelesThe forensic characteristics usually have more than two alleles
52 Mendel’s Third Law: Law of Dominance Some genes mask the effect of other genes, which then can pass on unchanged to reemerge when they are combined with another recessive gene.
53 The Spectrum of Dominance Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identicalIn incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varietiesIn codominance, two dominant alleles affect the phenotype in separate, distinguishable waysForensic Traits are codominant
54 P Generation Red CRCR White CWCW Gametes CR CW Pink CRCW F1 Generation 2CR12CWSperm12CR12CWEggsF2 Generation1CR2CRCRCRCW12CWCRCWCWCW
55 The Relation Between Dominance and Phenotype A dominant allele does not subdue a recessive allele; alleles don’t interactAlleles are simply variations in a gene’s nucleotide sequenceFor any gene, dominance/recessiveness relationships of alleles depend on the level at which we examine the phenotypeIf you look directly at DNA, you can always detect codominance.
56 Frequency of Dominant Alleles Dominant alleles are not always more common in populations than recessive allelesFor example, one baby out of 400 in the USA is born with extra fingers or toesThe allele for this trait is dominant to the allele for the more common trait of five digits per appendageIn this example, the recessive allele is far more prevalent than the dominant allele in the population
57 Multiple AllelesMost genes exist in populations in more than two allelic formsFor example, the four phenotypes of the ABO blood group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i.
58 Codominance is based on the carbohydrates being expressed differently on the red blood cells
59 Polygenic Inheritance Quantitative characters are those that vary in the population along a continuumQuantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotypeSkin color in humans is an example of polygenic inheritance
60 20/64 15/64 6/64 1/64 LE 14-12 AaBbCc AaBbCc aabbcc Aabbcc AaBbcc Fraction of progeny6/641/64
61 The Environmental Impact on Phenotype Nature and Nurture:The Environmental Impact on Phenotype
62 Relating Mendel’s Laws to Cells Law of SegregationPairs of characteristics (alleles) separate during gamete formationEach cell has two sets of chromosomes that are divided to one set per gamete.Law of Independent AssortmentThe inheritance of an allele of one gene does not influence the allele inherited at a second gene.Genes on different chromosomes segregate their alleles independently.
63 Offspring acquire genes from parents by inheriting chromosomes Children do not inherit particular physical traits from their parentsIt is genes that are actually inheritedGenes are carried on chromosomes.Mendel identified 7 sets of characters- One per each of the 7 chromosomes in peas, so his law worked out perfectly.Two characters on the same chromosome are linked together and would have messed up his law.
64 Terminology Review Genes are the units of heredity Genes are segments of DNAEach gene has a specific locus on a certain chromosomeGenetic variants at the same locus are alleles of one another.SNPs (Single Nucleotide Polymorphisms) are alleles of the same gene.
65 KeyMaternal set ofchromosomesPossibility 1Possibility 2Paternal set ofchromosomesTwo equally probablearrangements ofchromosomes atmetaphase IMetaphase IIDaughtercellsCombination 1Combination 2Combination 3Combination 4
66 8 Gamete Combinations vvvvvvvvvvvvvvvvvvvvvvvvvvvvvvv Maternal set of chromosomes (n = 3)2n = 6Paternal set ofchromosomes (n = 3)Two sister chromatidsof one replicatedchromosomesCentromereTwo nonsisterchromatids ina homologous pairPair of homologouschromosomes(one from each set)
68 Recall MeiosisHomologous pairs of chromosomes orient randomly at metaphase I of meiosisIn independent assortment, each pair of chromosomes sorts maternal and paternal homologues into daughter cells independently of the other pairsThe number of combinations possible when chromosomes assort independently into gametes is 2n, where n is the haploid numberFor humans (n = 23), there are more than 8 million (223) possible combinations of chromosomes
69 Random FertilizationRandom fertilization adds to genetic variation because any sperm can fuse with any ovum (unfertilized egg)The fusion of gametes produces a zygote with any of about 64 trillion diploid combinationsCrossing over adds even more variationEach zygote has a unique genetic identity
70 LE 13-11Prophase Iof meiosisNonsisterchromatidsTetradChiasma,site ofcrossingoverMetaphase IMetaphase IIDaughtercellsRecombinantchromosomes
71 Monohybrid Cross: - cross involving only one character. Monohybrid Cross: - cross involving only one character.
72 Results from Crosses F1 offspring - F2 offspring CONCLUSION the trait expressed was the same as that of one of the parental linestraits did not blendF2 offspringthe traits from both parents were expressed in a 3:1 ratiowhile the trait had not been expressed in the F1, it remained unchanged as it was passed from the P1 to the F1 and then to the F2 generation. CONCLUSIONTraits are inherited as discrete, separate units.
73 Mendel’s ConclusionsFactors (genes) that determine traits can be hidden or unexpressed.Dominant traits have a factor (gene) that is expressed in the F1 offspringRecessive traits have a factor (gene) that is not expressed in the F1 offspring
74 Mendel’s Conclusions2. Despite P1 and F1 generations appearing identical, they must be genetically different.Phenotype- observed properties of a traitGenotype- the genetic makeup of a traitPP1 and F1 seeds have the same phenotype but different genotypes
75 Mendel’s Conclusions3. Since the F1 offspring had factors (genes) for both smooth and wrinkled - then there must be at least 2 factors for every trait.Alleles- alternative forms of a geneGenotype- indicates the combination of alleles presentPhenotype- indicates the trait observedThese terms differentiate the observed form and the underlying alleles present at a particular gene.