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1 Genetics
2 Mendel s work Bred pea plants Cross-pollinated true breeding parents (P) then raised the seed & observed traits (F 1 ) Allowed offspring to cross-pollinate & observed next generation (F 2 ) P = parents F = filial In a typical breeding experiment, Mendel would cross-pollinate (hybridize) two contrasting, true-breeding pea varieties. The true-breeding parents are the P generation and their hybrid offspring are the F1 generation. Mendel would then allow the F1 hybrids to self-pollinate to produce an F2 generation. What did Mendel s findings mean? Traits come in alternative versions o Purple vs. white flower color (Alleles) Different alleles vary in the sequence of nucleotides at the specific locus of a gene Traits are inherited as discrete units For each character, an organism inherits 2 alleles, 1 from each parent Diploid organism inherits 1 set of chromosomes from each parent o Homologous chromosomes o Diploid = 2 sets of chromosomes o Like having 2 different editions of an encyclopedia What did Mendel s findings mean? Some traits mask others o Purple & white-flower colors are separate traits that do not blend Purple x white light purple Purple masked white o Dominant allele Fully expressed o Recessive allele No noticeable effect Non-functional protein 1
3 Genotype vs. phenotype Difference between how an organism looks & its genetics o Description of an organism s trait = phenotype o Description of an organism s genetic makeup = genotype Explain Mendel s results using: Dominant & Recessive and Phenotype & Genotype. Phenotype vs. Genotype 2 organisms can have the same phenotype but have different genotypes. 2
4 Mendel chose peas wisely Pea plants are good for genetic research o Available in many varieties with distinct heritable features with different variations Flower color, seed color, seed shape, etc. o 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 o Relatively simple genetically Most characters are controlled by a single gene Each gene has only 2 alleles, one of which is completely dominant to the other Mendel s Law of Heredity (#1) Law of Segregation o When gametes (eggs & sperm) are produced during meiosis, homologous chromosomes separate from each other o Each allele for a trait segregates (is packaged) into a separate gamete o What meiotic event creates the law of segregation? o And Mendel didn t even know DNA or genes existed! Test Cross It is possible to predict the genotype of an organism with a dominant phenotype? Cross-breed the dominant phenotype unknown genotype with a homozygous recessive (pp) to determine the identity of the unknown allele. 3
5 Monohybrid cross Some of Mendel s experiments followed the inheritance of single characters o Flower color o Seed color Dihybrid cross Some of Mendel s experiments followed the inheritance of 2 different characters o Seed color & seed shape Wrinkled seeds in pea plants with two copies of the recessive allele are due to the accumulation of monosaccharides and excess water in seeds because of the lack of a key enzyme. The seeds wrinkle when they dry. Both homozygous dominants and heterozygotes produce enough enzymes to convert all the monosaccharides into starch and form smooth seeds when they dry. Mendel s Law of Heredity (#2) Law of Independent Assortment o Each pair of alleles for each trait segregates into gametes independently = independent assortment. o 4 classes of gametes YR, Yr, yr, yr are produced in equal amounts. Review: Mendel s Laws of Heredity Law of Segregation o Monohybrid cross = single trait o Each allele for a trait segregates (is packaged) into separate gametes Established by Meiosis 1 Law of Independent Assortment o Dihybrid (or more) cross 2 or more traits o Each pair of alleles for each trait segregates into gametes independently Established by Meiosis 1 Some interesting historical facts While Mendel was acknowledged by his contemporaries as an outstanding plant breeder, his revolutionary genetics work was overlooked for 34 years. Mendel published Experiments on Plant Hybrids in In 1900, 16 years after Mendel s death, a number of scientists independently rediscovered his work. Charles Darwin, a contemporary of Mendel, proposed that evolution by natural selection was dependent on variation in the population, but Darwin was unable to propose a mechanism for how this variation was transmitted. The key was Mendel s work and nearly a century after Mendel published his findings historians found a copy of Mendel s paper in Darwin s study. He presumably never read it. 4
6 Chapter 14: Probability & Genetics Mendel s laws: Reflect same laws of probability that apply to tossing coins or rolling dice. Segregation Independent assortment Probability & Genetics Calculating probability of making a specific gamete is just like calculating the probability in flipping a coin o Probability of tossing heads? 50% o Probability making a P gamete Outcome of 1 toss has no impact on the outcome of the next toss o Probability of tossing heads each time? 50% o Probability making a P gamete each time? 50% Calculating Probability Rule of multiplication Chance that 2 or more independent events will occur together o probability that 2 coins tossed at the same time will land heads up ½ x ½ = ¼ o probability of Pp x Pp pp ½ x ½ = ¼ Calculating dihybrid probability Rule of multiplication also applies to dihybrid crosses o Heterozygous parent YyRr o Probability of producing yyrr? probability of producing y gamete = 1/2 probability of producing r gamete = 1/2 probability of producing yr gamete = ½ x ½ = ¼ probability of producing a yyrr offspring =¼ x ¼ = 1/16 1
7 Rule of Addition Chance that an event can occur 2 or more different ways o Sum of the separate probabilities o Probability of Pp x Pp Pp Extending Mendelian genetics Mendel worked with a simple system. o Peas are genetically simple. o Most traits are controlled by a single gene. o Each gene has only 2 alleles, 1 of which is completely dominant to the other. The relationship between genotype & phenotype is rarely simple. Incomplete dominance Heterozygotes show an intermediate phenotype o RR = red flowers o rr = white flowers o Rr = pink flowers make 50% less color 2
8 Co-dominance 2 alleles affect the phenotype in separate, distinguishable ways. o ABO blood groups o 3 alleles = I A, I B, and i. Both the I A & I B alleles are dominant to the i allele I A & I B alleles are codominant to each other. o Determines presences of oligosaccharides on the surface of red blood cells. Blood compatibility Matching compatible blood groups is critical for blood transfusions. A person produces antibodies against foreign blood factors = oligosaccharides. o If donor s blood has an A or B oligosaccharide that is foreign to the recipient, antibodies in the recipient s blood will bind to the foreign molecules. o Cause the donated blood cells to clump together & can kill the recipient. Pleiotropy Most genes are pleiotropic o One gene affects more than one phenotypic character Wide-ranging effects due to a single gene: Dwarfism (achondroplasia) Gigantism (acromegaly) Epistasis One gene masks another o 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 3
9 Polygenic inheritance Some phenotypes determined by additive effects of 2 or more genes on a single character o Phenotypes on a continuum o Human traits skin color height weight eye color intelligence behaviors Nature vs. Nurture Phenotype is controlled by both environment & genes A single tree has leaves that vary in size, shape & color, depending on exposure to wind & sun For humans, nutrition influences height, exercise alters build, suntanning darkens the skin, and experience improves performance on intelligence tests Even identical twins genetic equals accumulate phenotypic differences as a result of their unique experiences Thomas Hunt Morgan Morgan was an 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 o Trace a gene for eye color to a specific chromosome Discovery of Sex Linkage 4
10 Genes on sex chromosomes Y chromosome o SRY: sex-determining region Master regulator for maleness Turns on genes for production of male hormones Pleiotropy! X chromosome o Other traits beyond sex determination Hemophilia Duchenne muscular dystrophy Color-blind Sex-linked traits summary X-linked o Follow the X chromosomes o Males get their X from their mother o Trait is never passed from father to son Y-linked o Very few traits o Only 26 genes o Trait is only passed from father to son o Females cannot inherit trait X-inactivation Female mammals inherit two X chromosomes o One X becomes inactivated during embryonic development Condenses into compact object = Barr body X-inactivation & Tortoise shell cat o 2 different cell lines in cat Male pattern baldness Sex influenced trait o Autosomal trait influenced by sex hormones Age effect as well: onset after 30 years old o Dominant in males & recessive in females B = bald in males; bb = bald in females 5
11 Chapter 14: Studying Inheritance in Humans Pedigree Analysis Pedigree analysis reveals Mendelian patterns in human inheritance. Data mapped on a family tree. Recessive diseases The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all. o 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. Cystic Fibrosis Primarily whites of European descent Strikes 1 in 2500 births o 1 in 25 whites is a carrier (Aa) Normal allele codes for a membrane protein that transports Cl - across cell membrane o Defective or absent channels cause high extracellular levels of Cl - o Thicker & stickier mucus coats around cells o 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 1
12 Tay-Sachs Primarily Jews of eastern European (Ashkenazi) descent & Cajuns o Strikes 1 in 3600 births 100 times greater than incidence among non-jews or Mediterranean (Sephardic) Jews o 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 o Strikes 1 out of 400 African Americans. o Caused by substitution of a single amino acid in hemoglobin. o 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. o Substitution of one amino acid in polypeptide chain. Sickle Cell Phenotype 2 alleles are codominant o Both normal & abnormal hemoglobins are synthesized in heterozygote (Aa) o Carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stress Heterozygote advantage o 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. o Malaria Single-celled eukaryote parasite spends part of its life cycle in red blood cells. o 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. o High frequency of sickle cell allele in African Americans is vestige of African roots. 2
13 Genetics & culture Why do cultures have a taboo against incest? o 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. o But mating between close relatives increase risk. Consanguineous o Individuals who share a recent common ancestor are more likely to carry same recessive alleles. Chapter 15: Chromosomal Abnormalities Chromosomal Abnormalities Incorrect number of chromosomes o Nondisjunction Chromosomes don t separate properly during meiosis. o Breakage of chromosomes Deletion Duplication Inversion Translocation Nondisjunction Problems with the meiotic spindle cause errors in daughter cells. o Tetrad chromosomes do not separate properly during Meiosis 1. o Sister chromatids fail to separate during Meiosis 2. Baby will have wrong chromosome number o Trisomy Cells have 3 copies of a chromosome. o Monosomy Cells have only 1 copy of a chromosome. Alteration of Chromosome Number 3
14 Human Chromosome Disorders High frequency in humans o Most embryos are spontaneously aborted o Alterations are too disastrous o Developmental problems result from imbalance Certain conditions are tolerated o Upset the balance less = survive o Characteristic set of symptoms = syndrome Down Syndrome o Trisomy 21 3 copies of chromosome 21 1 in 700 children born in U.S. o Chromosome 21 is the smallest human chromosome. But still severe effects. o Frequency of Down syndrome correlates with the age of the mother. Sex chromosomes Human development more tolerant of wrong numbers in sex chromosome But produces a variety of distinct conditions in humans o XXY = Klinefelter s syndrome male o XXX = Trisomy X female o XYY = Jacob s syndrome male o XO = Turner syndrome female Klinefelter s syndrome o XXY male o 1 in every 2000 live births o Have male sex organs, but are sterile. o Feminine characteristics, tall, normal intelligence. Jacob s syndrome male o XYY Males o 1 in 1000 live male births o Extra Y chromosome. o Somewhat taller than average, more active. o Slight learning disabilities, delayed emotional immaturity. o Normal intelligence, normal sexual development. Trisomy X o XXX o 1 in every 2000 live births. o Produces healthy females. Why? Turner syndrome o Monosomy X or X0 o 1 in every 5000 births o Varied degree of effects Webbed neck Short stature, immature sterile females. 4
15 Changes in Chromosome Structure 5
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