Biology 110, Section 11 (J. Greg Doheny)

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1 Biology 110, Section 11 (J. Greg Doheny) Chapter 15 Chromosomal Basis of Inheritance Quiz Questions: 1. In linkage mapping, what is a Map Unit equivalent to? 2. Which insects determine sex using the X0 system, and which insects determine sex using the haploid/diploid system? 3. Which types of animals compensate for X chromosome dosage by creating a Barr Body? 4. What genetic phenomenon causes the orange vs. black patchwork of coat colours in Calico cats? 5. What is parthenogenesis? 6. What is a Barr Body? 7. Failure of sister chromatids to separate, leading to aneuploidy is called what? NOTES This week we will revisit linkage mapping, and also introduce some other topics related to genetics and chromosomes. Chromosomes and Linkage Mapping Chromosomes and Linkage Mapping: As mentioned in previous lectures, each gene has a locus, which is its physical location on a chromosome. Every organism has a unique number of chromosomes (humans have 23, fruit flies have 4 etc.) over which the genome is distributed. Diploid organisms have two of each chromosome, and therefore each individual may have one or two different alleles of each gene (although more than two alleles may exist in the overall population). If two genes are on two different chromosomes, they will sort independently during gametogenesis. If two genes are on the same chromosome, they will not sort independently during gametogenesis. They will sort together, unless there has been a crossover between them during Prophase I or Meiosis. Because the odds of having a crossover between two genes is proportional to the distance between them, the frequency of recombination can be used as an indirect method of measuring the distance between the genes. A 1% crossover frequency is called a recombination map unit. You can figure out the recombination frequency by doing a genetic crossing experiment, dividing the number of recombinant progeny by the total number of progeny (both parentals and recombinants ), and multiplying by 100%. (See Figure 15.10) A typical problem involving linkage mapping will give you two or three genes with two different alleles each. You ll be given the genotypes (or phenotypes) of the progeny, and you ll be asked to tell which genes are linked and which are not; and how far apart any linked genes are. If you are given three genes, the simplest way to do the problem is to compare the genes two at a

2 time. Then ask whether the recombinant genotypes represent 50% of the offspring. If the recombinants comprise 50% of the progeny, the genes are not linked. If the recombinants comprise less than 50% of the progeny, the two genes are linked, and the recombination frequency can be calculated by dividing the number of recombinant offspring by the total number of offspring. That s all there is to it! The trick is not to allow yourself to be distracted by details that draw your attention away from how to do the problem. I ll give you two examples, the first of which doesn t have many distracting details. The second one is not so straight forward, but the method of solving it is the same. Example 1: You cross two types of fungus to look at the relationships of three genes (A, B, and C). Genes A, B, and C each have two alleles (Aa, Bb, and Cc). You then look at the types of haploid spores that result from a cross between a fungus with genotype ABC and another with genotype abc. Because fungi are haploid, you don t have to worry about dominant alleles masking or hiding recessive alleles. P: ABC X abc F1: There are eight different types of offspring produced ABC ABc abc abc 5. 5 AbC 6. 5 Abc 7. 5 abc 8. 5 abc Compare the genes two by two, and tell which are linked and which are not. For those that are linked, determine how far apart they are in map units. Here s how to do it: start by comparing genes A and B. Count up the total number of parentals (AB and ab) and the total number of recombinants (Ab and ab), then see if the recombinants represent half the total. Do the same thing for A and C and (if necessary) B and C. Answer: A and B are linked, and are 20 map units apart. C is on a different chromosome. Why was that one so easy? Because A) by using haploid fungi, we didn t have to use any tricks to figure out what the genotype of each offspring was, B) I put the genes in an order that matched their linkage (A, B, and C), C) I conveniently made the numbers add up to 100, and D) one of the parentals had all the dominant alleles while the other had all the recessives. In the next problem I won t do any of those things, but the method of solving the problem is still the same. Example 2: Two strains of fungus are crossed with the following genotypes.

3 P: DEf X def F1: Eight types of progeny were produced def def DEf DeF Def DEF def def Determine which genes are linked, and how far apart any linked genes are. Additional linkage mapping problems can be found at the end of Chapter 15 of your textbook, and in Chapter 2 of another book called Schaum s Outline of Genetics available in the library. Other Topics Relating To Genes And Chromosomes Autosomal vs. X-Linked Genes: As mentioned in previous lectures, sex in mammals is determined by a pair of sex chromosomes (X and Y). Chromosomes that have nothing to do with determination of sex are called autosomes. Several genes are located on the X chromosome. Only a few genes are located on the Y chromosome. Some mutations to genes located on the human X chromosome cause human genetic diseases. Three examples are Colour Blindness, Muscular Dystrophy, and Haemophelia. The mutant genes responsible for all three of these genetic diseases are located on the X chromosome. Since men only have one X chromosome, the odds of them being able to mask, hide or compensate for a mutant version of one of these genes is lower than it is in women (who have two X chromosomes), meaning that these diseases are much more common in men than women. Male pattern baldness is also caused by a mutant gene carried on the X chromosome. Because men inherit their single X chromosome from their mother, this is what is meant when people say that baldness is determined by the mother s side of the family. Cystric Fibrosis and Achondroplasia are examples of autosomal genetic diseases, with the mutant genes being carried on the 7 th and 4 th chromosomes, respectively. Cystic Fibrosis is an autosomal recessive genetic disease, and Achondroplasia is an autosomal dominant genetic disease. X-inactivation in Mammals: Female mammals (including humans) have two X chromosomes, while males only have one. This would normally cause the genes that are located on the X chromosome to be transcribed twice as often in females as in males.

4 Mammals compensate for this difference in gene dosage by inactivating and compressing one of the two X chromosomes in females. Thus leaving both males and females with only one (functioning) X chromosome. The compressed, inactivated X is visible under the microscope, and is sometimes referred to as a Barr Body (in honour of Canadian scientist Murray Barr, who discovered this). The decision as to which of the two female X chromosomes to inactivate appears to be made (more or less) at random, and is made fairly early in development (during the blastula stage). One of the interesting effects of random X inactivation in female mammals is that it can lead to a patchwork expression of certain X-linked genes in females. The most famous example is a gene that determines coat colour in Calico cats. In Calico cats, a gene that determines coat colour is located on the X chromosome. The gene has two alleles, one coding for orange fur and the other for black fur. Heterozygous females have large patches of orange or black fur because one X or the other was inactivated early in development. Male Calico cats are either black or orange, but never patched, because they have only one X chromosome. (Question: What do you think happens in female humans who are heterozygous for the colour blindness alleles?) Random X-chromosome inactivation is not universal in animals. Mammals compensate for having two X chromosomes in females by inactivating one of the X chromosomes, so that males and females are equal. In insects, genes on the single male X are simply transcribed twice as often. Other methods of determining sex in animals: (Figure 15.6) Not all animals use an XY chromosome system to determine sex. Some insects (mostly the Orthoptera) use what is called an X0 system, where an insect will have either one X or two. XX insects are female, and X0 insects (where 0 indicates nothing ) are male. Aside from having only one copy of the X, male Orthopterans have two of all the other chromosomes. Other insects (mostly the hymenoptera) determine sex using a haploid vs. diploid system. Diploid insects are female (iequeen and worker bees), while haploid insects are male (drones). In such cases, the queen bee (or wasp) is fertilized by a male drone, and then spends the rest of her life laying either fertilized eggs that develop into worker bees, or unfertilized eggs that develop into male drones. Development of unfertilized eggs into fully functioning adult organisms is a genetic phenomenon called parthenogenesis. Polyploidy: Polyploidy refers to a genetic phenomenon whereby an organism inherits (and keeps) more chromosome sets than it originally had. (Example: a plant that is normally diploid, and has 10 pairs of chromosomes suddenly becomes tetraploid, having four instead of two of each of the 10 chromosomes.) Polyploidy happens almost exclusively in plants, which are relatively simple organisms. Doubling or tripling the number of chromosomes present can cause problems in more complicated organisms like animals.

5 Polyploidy is usually the result of a mistake during meiosis. Typically, a germ line cell will accidentally fail to divide properly, so that the number of chromosomes is not reduced when making gametes. For example, a germ line cell in a diploid plant fails to divide properly, giving rise to a gamete that is diploid instead of haploid. If this diploid gamete fuses with a regular haploid gamete it will create a plant that is triploid. If two accidental diploid gametes fuse, a tetraploid plant will be created. There are two types of polyploidy. a) Autopolyploidy: Where the plant has multiple copies of its own chromosomes. (Example: a diploid plant having ten chromosomes self-fertilizes when two accidental diploid gametes fuse, giving rise to a plant that has four of each chromosome instead of two of each. The same thing could then happen again, giving rise to a plant with six or eight copies of each chromosome.) b) Allopolyploidy: Where a plant has multiple copies of chromosomes from two different plants. (Example: Suppose a plant is diploid, and has 5 pairs of chromosomes. Another diploid plant has 10 pairs of chromosomes. If regular haploid gametes from each of these plants accidentally fused together, the resulting zygote would not be viable, because it would have 15 unpaired chromosomes. However, if each of these plants had a meiotic malfunction, so that each created a diploid gamete, and these two gametes fused, it would result in a viable plant with 15 pairs of chromosomes.) Aneuploidy: Aneuploidy refers to an organism that has an odd number of chromosomes. Usually one more or one less than normal. For example, Down Syndrome is an example of aneuploidy, where a human has an extra copy of chromosome 21. (Three copies of chromosome 21 instead of two.) Aneuploidy is the result of an error called a nondisjunction, that occurs during meiosis. A nondisjunction is where two sister chromatids fail to come apart during either Meiosis I or Meiosis II, giving rise to one cell that has n+1 chromosomes, and another that has n+2 chromosomes (see Figure 15.13). This, in turn, will give rise to fertilized zygotes that have either one too many or one too few chromosomes. In a normal diploid zygote, there should be two of each chromosome. If there are three copies of one of the chromosomes, it is called trisomy. If there is only one copy, instead of two, it is called monosomy. Thus, Down Syndrome, where there is an extra copy of chromosome 21, is also called Trisomy 21. Chromosome Re-arrangements: Chromosomes can be broken (by radiation, for example), but they are usually repaired by proteins whose job it is to rejoin the broken ends of a DNA strand. They sometimes make mistakes, however, and rejoin the broken pieces of DNA in the wrong order, or join a broken end to the wrong chromosome. Possible errors in chromosome repair can lead to the following (see Figure 15.14): a. Deletion: When a piece of a chromosome is broken out and lost. The two broken ends on either side of the lost piece are re-joined, but the piece that was broken out is lost. b. Duplication: When a piece of a chromosome is copied twice, by mistake.

6 c. Translocation: When a piece from one chromosome breaks off, and is accidentally rejoined to the wrong chromosome. i. Reciprocal Translocation: A special type of translocation where two different chromosomes swap arms in a reciprocal exchange. (Example: the p arm of Chromosome 10 is swapped for the p arm of Chromosome 5, and vice versa.) d. Inversion: Where a piece of a chromosome is broken out of the chromosome, rotated 180 degrees, and then re-inserted; leading to a chromosome that has a backwards piece in the middle. Two types of inversions are known: i. Paracentric Inversion: When the inversion does not include the centromere. ii. Paricentric Inversion: When the inversion does include the centromere. Inheritance of Organelle Genes: Some organelles, such as mitochondria and chloroplasts, have their own genomes. (Because they are actually separate, symbiotic organisms.) These organelles are divided equally among the two new daughter cells during cytokinesis, but no rearrangement of their genome takes place. When a sperm fertilizes an egg, it doesn t take any of its own mitochondria into the egg. Only the DNA (chromosomes) enter the egg. Thus, the only mitochondria that a fertilized zygote will have will be the mitochondria that the zygote s mother had, and which the mother deposited into the egg. Because there is no re-arrangement of the alleles in organelle DNA, a person will have the same mitochondrial DNA as his/her mother had, who will, in turn, have the same mitochondrial DNA that her mother had, and so on. For this reason, it is possible to look at just a person s mitochondrial DNA and determine exactly who their mother is. We all have exactly the same mitochondrial DNA as our mother, who, in turn, has exactly the same mitochondrial DNA as her mother, and so on. The same is true for determining who a boy s father is. A boy inherits his Y chromosome from his father, who, in turn inherited it from his father and so on. Thus, it is possible to determine who a person s mother is by looking at their mitochondrial DNA. It is also possible to determine who a boy s father is by looking at his Y chromosome DNA. However, it is not possible to determine (unambiguously) who a girl s father is by looking at her DNA, because the chromosomes she will have received from her father will be re-arrangements of his father s and his mother s chromosomes. It is possible to determine who her father is with a high degree of probability, but it is still only a probability. Determinations made from mitochondrial DNA and Y chromosome DNA, by contrast, are certainties, and not probabilities. Essay and Short Answer Questions: 1. What is an autosome? (5 points) 2. What is a Barr Body? (5 points) 3. What is Parthenogenesis? (10 points) PRACTICE QUESTIONS:

7 4. Briefly explain the differences in how sex is determined in A) Humans, B) Orthopteran insects, and C) Hymenopteran insects. (20 points) 5. Briefly explain the difference in how mammals vs. insects compensate for having two X chromosomes in females and only one in males. (10 points) 6. Briefly explain why the pattern of organelle gene inheritance ( like mitochondria) is not the same as the pattern of chromosomal gene inheritance. (20 points) Matching Questions: For each of the human genetic diseases listed below, state whether the disease is autosomal or X-linked. Furthermore, state whether it is an example of Aneuploidy or not, and if so, if it is an example of monosomy or trisomy. State whether each disease is: A) Autosomal or X-Linked B) Aneuploidy or not C) If Aneuploidy: Monosomy or Trisomy 1. Down Syndrome: Caused by an extra copy of Chromosome Klinefelter s Syndrome: A person who is phenotypically male, but has two X chromosomes and a Y (XXY). 3. Marfan Syndrome: Caused by a mutation to the FBN1 gene on Chromosome Triple X Syndrome: A person who is phenotypically female, but has three X chromosomes instead of two (XXX). 5. Familial Hypercholesterolemia: Caused by a mutation to the LDLR gene on Chromosome Turner Syndrome: A person who is phenotypically female, but has only one X chromosome instead of two. 7. Cystic Fibrosis (CF): Caused by a mutation to the CFTR gene on Chromosome Phenylketonuria (PKU): Caused by a mutation to the PAH gene on Chromosome Haemophelia: Caused by a mutation to either the Factor IX or Factor VIII genes on the X- chromosome. 10. Tay-Sachs Disease: Caused by a mutation to the HEXA gene on Chromosome Muscular Dystrophy: Caused by a mutation to Dystrophin gene on the X chromosome.

8 Match the terms to the definitions: a. Allopolyploidy b. Aneuploidy c. Autopolyploidy d. Barr Body e. Deletion f. Duplication g. Inversion h. Monosomy i. Nondisjunction j. Paracentric k. Pericentric l. Polyploidy m. Reciprocal n. Translocation o. Trisomy 1. Describes a diploid organism that has one extra chromosome. 2. Having one or more complete extra sets of chromosomes from the same organism (usually plants). 3. Where a chromosome has had a piece broken out of it, inverted by 180 degrees, and then inserted back in, creating a chromosome with a backwards piece in it. 4. A diploid organism that has one fewer chromosomes than normal. 5. When a piece is broken off of one chromosome, and accidentally joined to another. 6. General term for the state of having an odd number of chromosomes (ie-one too many or one too few). 7. A chromosome with a piece missing. 8. General term for organisms having too many or too few sets of chromosomes. 9. A chromosomal inversion that does not include the centromere. 10. A chromosome with a piece that was accidentally copied twice. 11. Having one or more complete sets of chromosomes from two or more different organisms (usually plants). 12. A chromosomal inversion that includes the centromere. 13. When two arms from two different chromosomes are exchanged. (The q arm of Chromosome 1 is exchanged for the q arm of Chromosome 10, for example.) 14. Failure of two sister chromatids to separate during Meiosis, leading to aneuploidy.