Mendelian Genetics PDF

MENDELIANS GENETICS 1  OVERVIEW ▪ 19th century: Before chromosomes or genes identified, Mendel set framework for Genetics (science of heredity) by studying the Garden Pea quantitatively with large sample sizes. ▪ Genes, carried inside chromosomes, a...

MENDELIANS GENETICS 1  OVERVIEW ▪ 19th century: Before chromosomes or genes identified, Mendel set framework for Genetics (science of heredity) by studying the Garden Pea quantitatively with large sample sizes. ▪ Genes, carried inside chromosomes, are the basic functional units of heredity with the capacity to be replicated, expressed, repressed, modified and mutated. ▪ Genes do not all obey tenets of Mendelian genetics, giving rise to Modern genetics ▪ Crosses between true-breading parents (P) that differed in 1 trait (color) produced 1st generation (F1) offspring that all expressed the trait of 1 parent. ▪ Dominant: refer to observable trait vs Recessive non-expressed trait ▪ When F1 offspring crossed, F2 generation exhibited both traits 3:1 ▪ Other crosses (characteristics such as height) generated same 3:1 ratio at F2 2  DEFINITIONS ▪ Model system: system with convenient characteristics used to study a specific biological phenomenon to be applied to other systems. (pea plant Pisum sativum) ▪ 1866 Experiments in Plant Hybridization has results of 30,000 pea plants. Demonstrated traits are transmitted independently of other traits and in dominant & recessive patterns. ▪ Continuous variation: Offspring appear to be a blend of their parents’ traits. This happens when many genes act together to determining a characteristic ▪ Blending theory of inheritance: asserted original parental traits were lost by blending in offspring. This is the idea of the time that contradicted Mendel. ▪ Discontinuous variation: traits that were inherited in distinct classes. Show they did not disappear, kept distinctiveness and could be passed on. 3  MENDEL’S MODEL SYSTEM ▪ Mendel’s peas are true-breeding ▪ They self-fertilize (offspring produced looks like parent; high in-breeding) ▪ Can avoid appearance of unexpected traits (recessive) from previous generation in offspring ▪ Matures within one season, so several generations could be evaluated over short time. ▪ Large quantities could be cultivated simultaneously. ▪ Large sample size = less impact of chance/randomness and more accuracy 4  MENDELIAN CROSSES ▪ Hybridizations: mating 2 true-breeding individuals that have different traits (color) ▪ Since peas are natural self-pollinators, he had to manually transfer pollen from anther of one mature pea variety to the stigma of a separate mature pea of a 2nd variety. ▪ Anther: part of stamen that produces pollen (male gametes) ▪ Stigma: sticky organ that traps pollen and allow it to move down the pistil to the female gametes ▪ Mendel removed the anther (tedious & non-lethal) of the plants receiving pollen, before they matured, to prevent them from self-fertilizing and confounding results ▪ P 0 = parental generation. 1st generation crosses ▪ F1 = offspring from P0 hybridizations. F2 = self-fertilization of F1 generation 5 CROSS BETWEEN TRUE-BREEDING PEA 6  OVERVIEW ▪ Phenotype: observable traits of an organism ▪ Genotype: organism’s underlying genetic makeup, the combination of alleles ▪ Homozygous: diploid (2 copies chromo) organisms carrying same alleles for a given trait ▪ Heterozygous: diploid organisms carrying different alleles for a given trait ▪ For a gene whose expression is Mendelian, homozygous dominant and heterozygous organism will look identical, displaying same phenotype. ▪ The recessive allele will only be observed in homozygous recessive individuals. 7  PUNNET SQUARE ▪ Monohybrid cross: fertilization occurring between 2 true-breeding parents that differ in only 1 characteristic ▪ Mendel concluded that each parent contributed 1 of 2 paired unit factors to each offspring and every possible combination was equally likely. ▪ Punnett square: applies rules of probability to predict possible outcomes of genetic cross and their expected frequencies. ▪ All possible combinations of parent alleles are listed along the top (for 1 parent) and side (other parent) of a grid, representing meiotic segregation into haploid gametes. ▪ Combination of egg & sperm are made in boxes in the table to show which alleles are combining ▪ Each box represents diploid genotype of zygote (fertilized egg) 8  PUNNET SQUARE ▪ Because each possibility is equally likely, genotype ratios can be determined from square. ▪ If pattern of inheritance (dominant or recessive) is known, phenotype can also be inferred ▪ Monohybrid cross of 2 true-breeding parents, each parent contributes one type of allele so only 1 genotype and phenotype is possible for F1 ▪ *Draw on board Punnet Square of P to F1 & F1 to F2 ▪ Reciprocal crosses: 2 possible heterozygous combinations produce offspring that are genotypically and phenotypically identical despite their dominant and recessive alleles deriving from different parents. (Ex: White plant fertilizing violet plant or vice versa.) ▪ Fertilization is a random event so expect each combination to be equally likely 9  HEREDITY ▪ Trait: variation in physical appearance of a heritable characteristic ▪ Mendel’s characteristics (7) were: height, texture, seed color, flower color, pea pod size, pea pod color and flower position. Each had 2 contrasting traits. ▪ Findings were consistent because of large sample size: ▪ Before starting, validated experiment by ensuring that the initial P generation was true-bred by witnessing self-crossed offspring displaying same traits as parent. ▪ Introduced pollen from a violet flower to stigma of white flowers. ▪ 100% F1 generation resulted in violet flower, not pale lavender as idea of the time: blend ▪ F1 self-fertilized and resulted in a ratio of 3 violet flowers to 1 white flower in F2 10  HEREDITY ▪ Mendel then reversed the experiment. He introduced pollen from white flowers to stigma of violet flowers. The F1 generation resulted in 100% violet flowers. The F2 generation that was self-fertilized resulted in ratio of 3 violet flowers to 1 white flower. ▪ Reciprocal cross: a paired cross in which respective traits of male & female in 1 cross become the respective traits of female & male in the other cross. ▪ Other 6 characteristics Mendel tested, behaved exactly as the colors referenced above ▪ Dominant traits: those inherited unchanged/expressed in a hybridization. ▪ Recessive traits: latent in the offspring of a hybridization. ▪ Recessive trait reappearing in progeny of F1 means that trait remained separate, it was not blended. 11  HEREDITY ▪ Mendel proposed plants possessed 2 copies of trait and that each parent transmit 1 copy to the offspring. ▪ Physical observation of a dominant trait means that genetic composition of organism included either 2 dominant versions of characteristic or 1 dominant & 1 recessive copy ▪ Conversely, observation of a recessive trait means that organism lacks any version of dominant characteristic 12  OVERVIEW ▪ The characteristics Mendel evaluated in pea plants were each expressed as 1 of 2 versions, or traits. ▪ Physical expression of characteristics accomplished through expression of genes (sequences of DNA) carried on chromosomes. ▪ Genetic makeup consist of 2 similar/homologous copies of each chromosome, one from each parent. ▪ Alleles: gene variations that are found at the same place on a homologous chromosome. ▪ Different alleles for a given gene in a diploid organism interact to express physical characteristics 13  TEST CROSS ▪ Test cross: method to determine whether an organism that is expressing dominant trait is heterozygote or homozygote. ▪ The dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic. ▪ If the dominant-expressing organism is a heterozygous, then all F1 offspring will exhibit a 1:1 ratio of heterozygotes and recessive homozygotes. ▪ This phenomena further validates Mendel’s postulate that pairs of unit factors segregate equally ▪ *Draw a test cross on the board between yellow and green seeds 14  PHENOTYPES & GENOTYPES ▪ Alleles: gene variations that are found at the same place on a homologous chromosome ▪ Mendel examined inheritance of genes with just 2 alleles but common to encounter more than that in a natural population ▪ Phenotype: observable traits of an organism ▪ Genotype: organism’s underlying genetic makeup, the combination of alleles ▪ Homozygous: diploid organisms have 2 identical alleles for that gene on their homologous chromosomes. (Example: Mendel’s true-bred parent generation) ▪ Heterozygous: diploid organisms carrying different alleles for a given trait. (Example: resulting offspring of F1 from Mendel’s experiment) 15  DOMINANT & RECESSIVE ALLELES ▪ In all 7 different characteristics he tested, one of the 2 contrasting alleles was dominant and the other recessive. ▪ Dominant = expressed unit factor vs recessive = latent unit factor ▪ Unit factors: are the genes on the homologous chromosome pairs. ▪ For a gene that is expressed in a dominant & recessive pattern, homozygous dominant & heterozygous organisms will look identical (different genotype, but same phenotype) ▪ Recessive allele will only be observed in homozygous recessive individuals ▪ Violet is dominant trait in flower will be denoted as V. Genotype heterozygous: Vv 16  OVERVIEW ▪ Law of dominance: Mendel proposed that genes are inherited as pairs of alleles that behave in dominant and recessive pattern ▪ Law of segregation: during meiosis, alleles separate such that each gamete is equally likely to receive either one of the 2 alleles present in diploid individual. (Monohybrid cross) ▪ Law of independent assortment: genes carried on different chromosomes sort into gametes independently of one another. (Dihybrid cross) ▪ Punnett squares can be used to predict genotypes and phenotypes of offspring involving one or two genes. ▪ Linked genes: genes located close together on same chromosome ▪ When genes located in proximity on same chromosome, alleles tend to be inherited together, unless recombination occurs. Mendel did not know about this factor. 17  PAIRS OF UNIT FACTORS ▪ Mendel generalized the results of his pea-plant experiments into 4 postulates that describe the basis of dominant & recessive inheritance in diploid organisms. ▪ There are some complex extensions of Mendelism that do not exhibit same F2 phenotypic ratios (3:1). These laws still summarize basics of classical genetics. ▪ Paired unit factors of heredity are transmitted faithfully from generation to generation by dissociation (gametogenesis) and reassociation of paired factors during fertilization. ▪ After cross peas with contrasting traits and found recessive trait resurfaced in F2, deduced hereditary factors must be inherited as discrete units. This finding contradicted belief at that time that parental traits were blended in offspring. 18  DOMINANT OR RECESSIVE ▪ Law of dominance: in a heterozygote, 1 trait will conceal presence of another trait for the same characteristic. ▪ Instead of both alleles contributing to phenotype, dominant allele expressed exclusively ▪ The recessive allele will remain latent but will be transmitted to next generation with the same odds as the dominant allele. ▪ Recessive trait is only expressed by offspring that have 2 copies of allele and will breed true wen self-crossed. ▪ In modern genetics have found other patterns of inheritance exist 19  EQUAL SEGREGATION OF ALLELES ▪ Law of segregation: paired unit factors (genes) must separate equally into gametes such that offspring have an equal likelihood of inheriting either factor ▪ 3 possible outcomes: homozygous dominant, homozygous recessive and heterozygous (which displays dominant trait) ▪ Because of the equal segregation of alleles we can use Punntet square to accurately predict offspring of parents with known genotypes ▪ During 1st division of Meiosis, homologous chromosomes with different versions of each gene are separated into daughter nuclei. This was not known during Mendel’s time 20  INDEPENDENT ASSORTMENT ▪ Law of independent assortment: genes do not influence each other with regard to sorting of alleles into gametes and every possible combination of alleles for every gene is equally likely to occur. ▪ In a dihybrid cross, the sorting of alleles for texture and color are independent events, so apply product rule. ▪ In meiosis I, the different homologous pairs line up in random orientations. Each gamete can contain any combination of paternal and maternal chromosomes. 21  LINKED GENES VS INDP ASSORTMENT ▪ Some allele combinations are not inherited independently of each other ▪ Genes located on separate non-homologous chromosomes will always sort independently ▪ Segregation of alleles into gametes can be influenced by linkage: genes located physically close to each other on same chromosome are more likely to be inherited as a pair. ▪ Because of recombination or crossover, it is possible for 2 genes on same chromosome to behave independently as if they are not linked ▪ Homologous chromosomes possess same genes in same linear order. However, alleles may differ. ▪ During Meiosis I, homologs align with each other and segments of genetic material are exchanged. Maternal and paternal alleles are combined onto same chromosome. 22  CROSSOVER ▪ As the distance between 2 genes increases, the probability of crossovers occurring between them increases and they will behave as if they were on separate chromosomes (independently). ▪ In a dihybrid cross, if tall and red genes were next to each other & short and yellow were close to each other, when the gametes are formed tall and red will move together resulting in no offspring that are tall and yellow. ▪ Do not follow Mendel’s independent assortment law. 23  LINKED GENES VS INDP ASSORTMENT ▪ Geneticist have used the proportion of recombinant gametes (the ones that shuffle parent information) as a measure of how far apart genes are on a chromosome. ▪ As a result, elaborate maps of genes on chromosomes have been constructed for a variety of organisms. ▪ It just so happened to be that the 7 sets of traits that Mendel tested are all on different chromosomes so he did not encountered linked genes that contradicted his independent assortment. 24  ALTERNATIVE TO DOMINANT/RECESSIVE ▪ Conclusions derived from Mendel’s experiment: ▪ Two units or alleles exist for every gene ▪ Alleles maintain their integrity in each generation (no blending) ▪ In the presence of dominant allele, recessive allele is “muted” and makes no contribution to phenotype ▪ Recessive alleles can be “carried” and not expressed by individuals ▪ Heterozygous individuals are sometimes called carriers. ▪ There are limitations to the fundamental principles of Mendelian genetics. An extension must be considered because some organisms exhibit more complexity. 25  PEDIGREE ▪ Many human diseases are genetically inherited ▪ A “healthy” person in a family in which some members suffer from a recessive genetic disorder (might be a carrier) may want to know if they have a risk of passing the disorder on to their offspring. ▪ Test crosses would be unethical and impractical. ▪ Geneticists use pedigree analysis to study inheritance pattern of human genetic disorder ▪ The information gained from pedigrees makes it possible to determine the nature of genes and alleles associated with inherited human traits 26  X-LINKED TRAITS ▪ In humans and many other animals, sex of individual determined by sex chromosomes ▪ Sex chromosomes: 1 pair of non-homologous chromosomes ▪ Autosomes: Non-sex chromosomes. In humans, pairs #1 through 22 ▪ Y chromosome has small regions of similarity so that it can pair with X during meiosis ▪ Y chromosome is much smaller. As a result, higher incidence of genetic diseases for males because do not have backup for faulty X genes ▪ X-linked: gene being examined is present on X chromosome, but not on Y ▪ Hemizygous: males have only 1 allele for any X-linked characteristic ▪ Reciprocal crosses do not produce same offspring ratios. 27  X-LINKED TRAITS ▪ Drosophila, also known as fruit flies encode the eye-color gene in the X chromosome ▪ The wild-type eye color is red (X^R) and is dominant to white eye color (X^r) ▪ Reciprocal crosses do not produce same offspring ratios: ▪ Genotype for males: X^R Y or X^r Y ▪ Genotype for females: X^R X^R, X^R X^r or X^r X^r ▪ When P male has white or red eyes and female is homozygous red-eyes, all offspring will display red eyes whether they are male or female ▪ Heterozygous female with red eye male, would produce only red eyes female and both red and white-eyed males ▪ Homozygous white-eyed female and red-eye male = F1 only heterozygous red females & only white-eyed males. F2 half females & males red-eye and half female & males white-eyed. 28  HUMAN SEX-LINKED DISORDERS ▪ When female parent is homozygous for a recessive X-linked trait, she will 100% pass on trait to offspring. ▪ The male offspring are 100% destined to express the trait as they only inherited the Y from the father. ▪ Alleles for conditions: color blindness and hemophilia are X-linked ▪ Heterozygous females can be “carriers” and not exhibit any phenotypic effect ▪ Pass on disease to half of their sons & pass on carrier status to half their daughters ▪ In birds, female is the sex with the non-homologous sex chromosomes so they exhibit most incidence of disease, instead of being carrier. 29  HUMAN SEX-LINKED DISORDERS ▪ X-linked recessive disorders are disproportionately observed in males because they only require 1 copy of the mutant allele to be affected. ▪ Females must inherit recessive X-linked alleles from both parents in order to express the trait ▪ When females inherit 1 recessive X-linked mutant allele and 1 dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. ▪ Female carriers can contribute trait to their sons, resulting in son exhibiting trait or they can contribute recessive allele to their daughters, which if father was not sick, results in daughters being carriers of trait too. ▪ Y-linked disorders exist. Exclusive to males, but typically associated with infertility so they are not transmitted to subsequent generations. 30 HUMAN SEX-LINKED DISORDERS 31  LETHALITY ▪ Large proportion of genes in an individual’s genome are essential for survival ▪ Sometimes, a nonfunctional allele for an essential gene can arise from a mutation and be transmitted in a population as long as individuals with this allele also have a wild-type, functional copy that is able to sustain life so it is dominant. ▪ Recessive lethal: 2 heterozygous organism that carry nonfunctional essential gene expected to pass down 25% of the time double (homozygous) recessive trait resulting in embryo death or producing an organism that will die sometime after birth. ▪ In other instances, recessive lethal allele might exhibit dominant, but not lethal phenotype in the heterozygote. (Example: the manifestation of a malformation) ▪ Dominant lethal: an allele is lethal in both homozygote and heterozygote. It can only be transmitted if lethality phenotype occurs after reproductive age. (Example: Huntington’s nervous system degeneration). 32