3. c.* Students know how to predict the probable mode of inheritance from a pedigree diagram showing phenotypes.

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1 3. A multicellular organism develops from a single zygote, and its phenotype depends on its genotype, which is established at fertilization. As a basis for understanding this concept: 3a. Students know how to predict the probable outcome of phenotypes in a genetic cross from the genotypes of the parents and mode of inheritance (autosomal or X-linked, dominant or recessive). Monohybrid crosses, including autosomal dominant alleles, autosomal recessive alleles, incomplete dominant alleles, and X-linked alleles, can be used to indicate the parental genotypes and phenotypes. The possible gametes derived from each parent are based on genotypic ratios and can be used to predict possible progeny. The predictive (probabilistic) methods for determining the outcome of genotypes and phenotypes in a genetic cross can be shown by using Punnett Squares and probability mathematics. 3. b. Students know the genetic basis for Mendel s laws of segregation and independent assortment. Mendel deduced that for each characteristic, an organism inherits two genes, one from each parent. When the two alleles differ, the dominant allele is expressed, and the recessive allele remains hidden. Two genes or alleles separate (segregate) during gamete production in meiosis, resulting in the sorting of alleles into separate gametes (the law of segregation). 3. c.* Students know how to predict the probable mode of inheritance from a pedigree diagram showing phenotypes. Notes: Major concepts: Notes 1. The science that describes inheritance of in-born characteristics is genetics. The term "genetics" was coined around the turn of the century, but much of the basic theory of genetics derives from the work of a monk who lived in Bohemia in the middle of the 19th century. The monk's name was Gregor Mendel 2. Mendel used the common garden pea for his experiments in heredity. Studying a small number of easily observed traits (phenotypes), Mendel was able to deduce the existence of factors in cells that controlled their propagation from one generation to the next (we now call them genes). 3. Mendel hypothesized that each organism receives one gene from each parent. He showed that these genes can impose their phenotype on the organism (dominant) or the phenotype may not be seen, become cryptic (recessive) though it can be revealed as still present by its phentoype reappearing in subsequent generations. 4. By mating peas with distinct phenotypes specified by alternative states of genes he was able to demonstrate that the ratio of phenotypes produced in successive generations can be easily predicted. The scientific study of inheritance began in the mid 1800's with the experiments of Gregor Mendel. Mendel worked out the mathematical rules for the inheritance of characteristics in the garden pea. Thus began the science of genetics. Mendel's experiments with peas (Pisum sativum) provided the basis for genetics Mendel was a monk in a monastery in what is now the Czech Republic (more specifically, Moravia) but was then, in the mid-19th century part of Austria. He became interested in the nature of inheritance, and performed experiments with the system which was easiest for him to use, the garden pea. These experiments were eventually presented to scientific societies and published in They were not really appreciated for several decades, and were rediscovered by Bateson, among others, who published a book describing his results in Mendel was not a member of the scientific elite of his day, though they were aware of his work through its publication. It's likely that they were not able to fully appreciate

2 the work. Bateson, who was a professor at Cambridge University, was a member of that elite, and was able to popularize his concepts and provide additional support for them. Mendel did experiments in what was termed "hybridization" at the time. He studied what happened when "true breeding" plants were crossed to each other. True breeding plants are plants that always produce offspring that look the same, e.g. plants with yellow peas producing more plants with yellow peas. People thought at the time that hereditary information from each parent were mixed with each other in their offspring. Mendel's leap was to imagine that heredity consisted of units. Hereditary units could be associated with particular observable traits (e.g, those yellow peas). Each parent contributed one unit to the offspring, so there were two of each-one maternal and one paternal How did Mendel come to this hypothesis? It is hard to know since the abbot that succeeded Mendel was a lifelong rival who opposed Mendel's scientific experiments. The new abbot destroyed all of Mendel's notebooks on his death! One conjecture is that Mendel noted that there was one obvious phenotype which had an "either/or" nature: gender. Offspring of any animal, including humans, are either male or female. They didn't show a "mixture" of sexual characteristics. In large populations of animals the ratio of male to female is 1:1. This suggests a simple model of sex determination in which one of the sexes carries a single unit which determines maleness (or femaleness). A child receiving that unit was that gender, one not receiving it was the other. Mendel wanted to demonstrate the existence of such a unit. His work didn't directly involve gender since pea plants do not have a gender (their flowers have both male and female aspects). Instead, he studied other observable traits: flower color, plant height, flower position, pod or pea color, pea shape, etc. With these simple observable traits he was able to demonstrate that genetic units existed, and that they were inherited in pairs, one from each parent. To discuss Mendel's results it helps to use the genetic nomenclature. Gene: a unit of hereditary information; each is at a unique location on a chromosome, also called a locus. Allele: genes can come in various forms which carry distinct information-each distinct form is called an allele. o A gene concerned with pea color might specify yellow versus green o A particular form of the gene specifying green would be called an allele o There can be multiple forms which have give the same observable trait; each is a unique allele Phenotype vs. genotype: the observable effect of an allele is its phenotype; genotype is just the nature of the genes carried by an individual (for example, identifying what alleles he carries). Homozygous vs. heterozygous: since each individual carries two of these alleles, they can either be identical (homozygous) or different (heterozygous) o "Homo" means same while "hetero" means different Dominant vs. recessive: if an individual carries two alleles with different phenotypes (e.g., yellow peas versus green peas) he can not express both of them-they are mutually exclusive o Most of the time one is expressed to the exlusion of the other; the one whose phenotype is expressed is dominant (e.g., when a yellow and green allele are present the peas appear yellow-yellow is dominant). o The allele whose phenotype is not expressed is recessive (green is recessive) In addition to these genetic terms there are some common genetic symbols: Dominant and recessive genes are represented by uppercase and lowercase letters, respectively o The dominant allele might be referred to as "A" while the recessive is symbolized by an "a" o A dominant homozygote would be AA, a recessive homozygote is aa; the heterozygote is Aa o Another gene could be symbolized as B and b To track inheritance the generations of a genetic cross are termed: o P parental generation o F1 first-generation offspring o F2 second-generation offspring Alleles: versions of each other

3 An average chromosome has many locations (loci) were a specific genetic trait must exist (like the letters of the alphabet have a particular order). The gene inhabiting a particular chromosomal locus is an allele to another gene found at the same location on the other homologous chromosome. Genes found at the same chromosomal locus, coding for variations of the same trait are alleles. Each trait studied by Mendel had only 2 variations or characteristics. Laws of Dominance and Segregation Mendel chose peas to study because seeds for many of the traits he used were commercially available and were guaranteed true breeding. If a plant is true breeding for a particular characteristic all the offspring will have the same characteristic generation after generation. A plant with purple flowers when crossed to another purpleflowered plant will produce only purple-flowered offspring. True breeding organisms can be obtained by inbreeding for many generations. This is a form of artificial selection pursued by humans for hundreds of years in an effort to increase crop yields and other beneficial characteristics. Mendel's Experimental Procedures Mendel began his experiments by investigating a single trait such as flower color. Only two characteristics white and purple color were used. He would take a plant true-breeding for purple flowers and cross it with a plant true-bred for white flowers. This was the P or parental generation. All the offspring of this first cross were called the F 1 generation. He discovered that the purple characteristic was dominant and the white flower was recessive, since the only flower color in the F 1 generation was purple. A dominant trait is expressed regardless of the other allele of the gene pair. Mendel's Law of Dominance -- Only the dominant characteristic appears in the F 1 offspring of a cross between two pure lines. The next step separated Mendel from all other scientists studying heredity during his life. He allowed the F 1 generation to cross breed. He discovered that in the F 2 generation for every plant with white flowers he counted 3

4 with purple flowers. In fact for every trait he studied the ratio of dominant to recessive characteristics was always 3:1 in the F 2 generation. From this information Mendel hypothesized that phenotype (dominant and recessive characteristics - purple and white flowers) must be controlled by genotype (the two genetic factors inherited separately from the two parents). He realized that members of the F 1 generation had received a factor from both members of the parent generation; otherwise the recessive trait could not reappear in members of the F 2 generation. Mendel also realized that these factors had to separate from one another at some point during reproduction. Today we know this separation (segregation) occurs during anaphase I of meiosis, as homologous chromosomes are pulled apart. Mendel's Law of Segregation states that during reproduction the two alleles that control each trait segregate and move to different gametes. Alleles and Genotype If both alleles code for the same characteristic the genotype of the diploid organism is homozygous. True breeding organisms are homozygous for a given trait. If the two alleles code for different characteristics the organism is heterozygous for the trait in question. The F 1 offspring are all heterozygous for the trait in question. Genotypes and Sex Chromosomes The genotype is an organism's unique makeup. The genotype for a particular characteristic is expressed as two letters representing the two genes or chromosomes which are normally involved in heredity. The genotype for an organism's sexual characteristics is expressed as XX for the female trait and XY for the male sexual trait. X and Y represent the two chromosomes involved The phenotype is an organism's outward appearance. Phenotypes can be altered by the environment without changing the genotype. For instance many animals have different coat colors for winter and summer but their genotype stays the same. In humans and many other species it is the male gamete that determines the sexual characteristic of the offspring. *If the sperm carries an X chromosome and fertilizes an egg the offspring will be female (XX). But if the sperm carries a Y chromosome and fertilizes an egg the offspring will be a male (XY).

5 Fertilization is the fusion of a male and female gamete (egg and sperm) to form a zygote (fertilized egg) that begins all eukaryotic life.. Most species of plant have both male and female sex organs on a single plant. Meiosis separates the X and Y chromosomes into separate sperm (X sperm or Y sperm). Genetic Recombination The genes in any particular chromosome are all linked together as part of the same continuous strand of DNA. These genes form a linkage group. The linkage group can be rearranged during prophase I of meiosis because crossing over takes place. Cross over events between homologous chromosomes break up linked groups of genes increasing the variety of offspring possible. Since homologous chromosomes are very similar they can align and the segments of adjacent chromatids that get entangled may break and during repair switch places. (see below)

6 This exchange of genetic material results in genetic recombination. A fundamental method to increase variations in offspring and provide a greater chance of survival when environmental conditions change. How genes work Every cell has a full compliment of chromosomes, which means that technically it has all your genes whether it needs them or not. In order to function correctly the cell must turn many genes off. Genetic Changes Chromosomes are very large molecules -- long thin strands of DNA. Any change in the billions of atoms making up DNA can change the information it carries as part of its structure. Such changes do occur although rarely. Mutations are often detrimental, especially when the organism is complex. But only mutations can provide the variation on which life depends (in order to adapt to environmental changes). Various natural processes an chemicals in the environment or man-made substances can cause mutations. These substances are called mutagens. Some mutagens are: cigarette smoke asbestos aromatic solvents like benzene viruses radioactivity X-ray and UV light Now matter how hard you try, it is probably impossible to eliminate all mutagens in your life.

7 Hundreds of mutagens have been classified, some weak requiring large doses while others are effective in very small amounts. Some mutagens can even be considered useful under certain circumstances. The next section reviews the various types of mutation. Gene Mutations Point mutations are the most common type of gene mutation. They result when a single change is made in the nucleotide sequence. Normally only one nucleotide is affected but sometimes a small number of nucleotides are involved. Three examples of point mutations are: 1. Substitution - one nucleotide replaces another Original Sequence mutation... A T C C C G A T A C C G... A is substituted for C 2. Deletion - one or more nucleotides are lost from the gene Original Sequence mutation... A T C C C G A T. C C G... In this example nucleotide C is lost. The result produces a chaotic jumble of new nonsense "words" in the code. The resulting protein is useless. 3. Addition - one of more nucleotides are inserted in to the gene sequence Original Sequence mutation... A T C C C G A T C A C C G... Nucleotide A is inserted. The result is generally a completely defective protein. Deletion and addition point mutations are known as frameshift mutations because of the shift in the genetic code. It the number of nucleotides added or deleted is not divisible by 3 most of the amino acids after the mutation will not be those originally coded for. Why? Chromosome Rearrangements Chromosomes may also be mutated. Viruses and certain chemicals are usually involved. Two classes of chromosome changes are: 1. Rearrangements which do not change the amount of genetic information. These mutations include: A. Chromosome inversion. The broken section of DNA is reinserted backwards B. Translocation. The broken piece of chromosome is attached to a different chromosome. 2. Deletion or addition of genetic Information.

8 Deletions may include only part of a single gene or as much as an entire chromosome. The effect is usually adverse. Addition of genetic information is key to major genetic changes, and can even result in new species within a single generation. The most common method is for one or more chromosomes to remain together and not separate during meiosis. Thus one gamete gets 2 copies of the chromosome(s) while the other receives none. This process is called nondisjunction. When an entire set of chromosomes fail to separate during meiosis some of the offspring may have 4 times the number of chromosomes as the original haploid gametes. This condition is called polyploidy. Many organisms actually can control the amount of mutation they are subject to. This might seem to be a bad strategy, but when the environment is harsh and each individual can produce millions of offspring the occasional beneficial mutation can save the species from extinction. A special kind of linkage: sex linkage Because some of the chromosomes have a special role-in determining gender-the genes on those chromosomes have a special kind of linkage called sex-linkage. Because there are two such chromosomes in humans and many other animals this linkage can be separated into X-linkage and Y-linkage. As it turns out, the Y chromosome has very few genes that cause an observable phenotype, therefore most sex-linkage is in fact X-linkage What does X-linkage look like? The classic example of sex-linkage genetics as discovered by Thomas Morgan about 90 years ago involved the White mutation of Drosophila melanogaster (termed w). Morgan found a spontaneous mutation which changed the flies' eyes from brick red to white. When males carrying this mutation were mated to wild-type females the F1 flies all had red eyes The females of this cross were mated with wild-type males. The

9 progeny of this cross included all red-eyed females, but the males were 50% red-eyed and 50% white-eyed. One of the F2 females when mated to a white-eyed male gave 50% white-eyed females, and 50% white-eyed males; crossing these gave a 100% white eyed stock (males and females). What is important in this example is that the phenotypes differed between the two sexes. How did this happen? The answer to what was going on was that the recessive w mutation was located on the X chromosome. The F1 females had one w X chromosome and one W+ X chromosome. Since the F2 males from a cross to wild-type got their X chromosomes from this mother, half got the w chromosome and half the W+ chromosome. Since there is no copy of White on the Y chromosome, the males were 50% white-eyed. Mating these back to the F1 females allowed the generation of a w/w female which could mate with a w/y male to produce a true breeding stock with w on every X chromosome The F1 females could be thought of as "carriers" of the white mutation. The effect can not be seen in them, yet half of their sons are affected by the mutation. This same method of inheritance can be seen in human X-linked traits--here are three examples: Hemophilia--an inherited form of hemophilia was passed through the family of the British queen Victoria. We know that the mutation occurred in Victoria since none of her ancestors showed the disorder. Victoria had one hemophelic son, and his daughter in turn had a hemophelic son. Two of Victoria's non-hemophelic daughters were carriers and had hemophelic sons, and hemophelic grandsons (including the heir to the Russian throne, the Crown Prince Alexis)

10 Red-Green color blindness--the genes for the two proteins which recognize red and green light are located on the X chromosome. The two genes are located near to each other and mutations often occur which eliminate one or the other of the pair. The fact that they are located on the X means that color blindness is much more common in males Pattern baldness--the form of baldness in which hair is lost first from the crown of the head is another X-linked trait