The information in this document is meant to cover topic 4 and topic 10 of the IB syllabus. Details of meiosis are found in Notes for Cells. Mendelian Genetics Gregor Mendel was an Austrian monk, who, in the 1860 s, performed many experiments in which he crossed Pisum sativum, the common garden pea. With no formal scientific training, and no knowledge of mitosis, genes or chromosomes, he was able to determine that characteristics did not blend on crossing, but retained their identities, and were inherited in fixed mathematical ratios. Law of Unit Characters: There are units in the cell that are responsible for traits (characteristics); these units come in pairs. Law of Segregation: The characteristics of an organism are controlled by pairs of alleles which separate in equal numbers into different gametes as a result of meiosis. Law of Independent Assortment: Two or more pairs of alleles segregate independently of each other as a result of meiosis, provided the genes concerned are not linked by being on the same chromosome. Inheritance of Characteristics in Peas (Pisum sativum) Image from http://www.anselm.edu/homepage/jpitocch/genbio/peachar.jpg A. De Jong/TFSS 2009 Page 1 of 14
Before we continue some definitions: Genome = the whole of the genetic information of an organism Gene = a heritable factor that controls a specific characteristic Allele = one specific form of a gene, differing from other alleles by one or a few bases only and occupying the same gene locus as other alleles of the gene Locus = the particular position on homologous chromosomes of a gene (its address on the chromosome) Genotype = the alleles of an organism Phenotype = the characteristics of an organism Homozygous = having two identical alleles of a gene Heterozygous = having two different alleles of a gene Dominant allele = an allele that has the same effect on the phenotype whether it is present in the homozygous or heterozygous state Recessive allele = an allele that only has an effect on the phenotype when it is present in the homozygous state Codominant alleles = pairs of alleles that both affect the phenotype when present in a heterozygote Carrier = an individual that has one copy of a recessive allele that causes a genetic disease in individuals that are homozygous for this allele Test cross = testing a suspected heterozygote by crossing it with a known homozygous recessive individual Monohybrid Cross A monohybrid cross is one that specifically looks at the inheritance of one characteristic. Example: In Pisum sativum, a smooth seed is produced by a dominant allele, S, while wrinkled seeds are produced by the recessive allele, s. In a cross between a homozygous smooth and a wrinkled plant, the F1 generation will all have smooth seeds: P1: SS x ss gametes: S s F1: all Ss (smooth) Crossing the F1 plants among themselves produces the F2 generation this cross is illustrated by the Punnett square at right: Image from http://www.emc.maricopa.edu/faculty/farabee/biobk/mono2.gif The genotypic ratio is 1 SS : 2 Ss : 1 ss. The phenotypic ratio is 3 smooth : 1 wrinkled. A. De Jong/TFSS 2009 Page 2 of 14
In any monohybrid cross, the ratio of dominant to recessive phenotypes will always be 3:1, as long as there is one dominant and one recessive allele. Dihybrid Cross A dihybrid cross is one that specifically looks at the inheritance of two characteristics. Example: In Pisum sativum, a smooth seed is produced by a dominant allele, S, while wrinkled seeds are produced by the recessive allele, s. Yellow seeds are produced by the dominant allele, Y, while green seeds are produced by the recessive allele, y. In a cross between a homozygous smooth, yellow plant and a wrinkled, green plant, the F1 generation all have smooth, yellow seeds: P1: SSYY x ssyy gametes: SY sy F1: all SsYy (smooth, green) Crossing the F1 plants among themselves produces the F2 generation, as illustrated by the Punnett square to the right. Image from http://www.emc.maricopa.edu/faculty/farabee/biobk/dihyb2.gif In any dihybrid cross, the phenotypic ratio will always be 9:3:3:1, as long as there is one dominant and one recessive allele for each gene. 9 are the dominant phenotype for both genes 3 are the dominant phenotype for one gene 3 are the dominant phenotype for the other gene 1 is the recessive phenotype for both genes A. De Jong/TFSS 2009 Page 3 of 14
Test Crosses Because an individual displaying the dominant phenotype could be either homozygous or heterozygous, geneticists have designed the test cross, which is used to determine the genotype of a phenotypically dominant individual. In a test cross, the individual of uncertain genotype is crossed with one that is homozygous recessive: Image modified from http://porpax.bio.miami.edu/~cmallery/150/mendel/c8.14x7.testcross.jpg A monohybrid test cross will result in a 1:1 ratio if the dominant parent is heterozygous. A dihybrid test cross will result in a 1:1:1:1 ratio if the dominant parent is heterozygous. Variations on a Theme So far, we have examined the inheritance of genes that have two alleles, one dominant and one recessive. This is not always the case. Codominance When alleles are codominant, the heterozygous genotype results in a phenotype that is different from either of the homozygous forms. The hybrid may be a blended version of the two, or express both equally. Example: In a certain type of flower, a cross between a red- flowered plant and a white- flowered plant produces only pink plants. A. De Jong/TFSS 2009 Page 4 of 14
P1: RR x WW gametes: R W F1: all RW (pink) When the pink plants are crossed among themselves, all three colours are produced: gametes: RW x RW R,W R,W F2 R W R RR RW W RW WW Image from http://www.nkellogg.com/codominance.gif In this case, the phenotypic & genotypic ratios for the F2 plants are both 1:2:1. 50% of the F2 plants are the hybrid pink phenotype. Multiple Alleles Some genes have more than two alleles. The human ABO blood groups are a well- known example. Blood group (or type) is due to presence of certain marker proteins on the surface of red blood cells (RBCs). These proteins are sometimes called antigens, because if the wrong blood type is given to someone, it can cause formation of antibodies that attack the foreign red blood cells. Think of it as someone wearing a TFSS lanyard at Leger. A. De Jong/TFSS 2009 Page 5 of 14
The marker proteins (A and B) are coded for by different alleles of the same gene, I A and I B. These alleles are codominant, because if both are present, they are both expressed, and the RBCs have both marker proteins on the surface of the plasma membrane. The third allele, i, is recessive to I A and I B because it does not code for a protein so if it is present in a heterozygote, the other allele, I A or I B will dominate by producing its protein. The possible phenotypes are dependent upon the genotypes, as follows: Genotype Phenotype Can Give To Can Receive From I A I A I A i A A, AB A, O I B I B I B i B B, AB B, O I A I B AB AB AB, A, B, O Universal acceptor ii O AB, A, B, O O Universal donor Example: If Harpreet has type A blood, and Trinh has type B blood, and both their fathers had type O blood, what are the possible blood types of any children they have together? Note: Because their fathers both have type O blood, they both must be heterozygous. P1: I A i x I B i gametes: I A, i I B, i F1 I A i I B I A I B I B i i I A i ii The phenotypic ratio is 1:1:1:1, with all four blood groups represented. Another Example: In rabbits, there are four alleles for the gene that controls fur colour. The wild type, agouti, (C), is dominant to the other three. Albino (c) is recessive to the other three. Chinchilla (c ch ) is dominant to Himalayan (c h ): C > c ch > c h > c What would be the result of a cross between an agouti/chinchilla hybrid, and a Himalayan/albino hybrid? P1: Cc ch x c h c gametes: C, c ch c h, c F2 C c ch c h C c h c ch c h c C c c ch c There are four genotypes, present in equal numbers (1:1:1:1). Phenotypes: 50% agouti, 50% chinchilla A. De Jong/TFSS 2009 Page 6 of 14
Sex-Linked Alleles The sex chromosomes are responsible for controlling gender. In humans, females have two X chromosomes, while males have one X and one Y chromosome. Alleles located on one of these two chromosomes will display different inheritance patterns than alleles located on the autosomes (in humans, the first 22 chromosomes those not gender- determining). Sex linkage occurs when an allele exists on one of the sex chromosomes (X or Y in humans). Two common examples of sex- linked recessive alleles in humans are colour- blindness and hemophilia, both located on the X- chromosome. Females must be homozygous for these conditions to express the condition, as presence of the dominant allele on their second X- chromosome would result in the normal condition. Heterozygous females are called carriers. Males, since they only have one X- chromosome, will express the condition if they receive the recessive allele, since there is no corresponding dominant allele on the Y- chromosome. A male with the recessive allele is said to be hemizygous. Example A human female "carrier" who is heterozygous for the recessive, sex- linked trait causing red- green colour blindness, marries a normal male. What proportion of their male progeny will have red- green colour blindness? P1: X H X h x X H Y gametes: X H, X h X H,Y F2 X H Y X H X H X H X H Y X h X H X h X h Y Half the boys will be colour blind. Girls: 50% normal, 50% carrier Boys: 50% normal, 50% colour blind Pedigree Analysis A pedigree chart is a diagram that tracks the inheritance of a specific trait through a family. Analysis of a pedigree chart can help you determine whether a trait is dominant or recessive, autosomal or sex- linked. By convention, the following symbols are used: Image from http://www.ucl.ac.uk/~ucbhjow/b241/mendel_1.html (as are pedigrees on pg 8) A. De Jong/TFSS 2009 Page 7 of 14
Example 1 Autosomal Dominant Characteristics of a pedigree for an autosomal dominant trait: Trait appears in all generations Trait appears in offspring if only one parent displays the trait Trait appears equally in both genders Example 2 Autosomal Recessive Characteristics of a pedigree for an autosomal recessive trait: Trait does not appear in all generations Trait may appear in offspring of parents who do not express the trait Trait appears to skip generations Trait appears equally in both genders Pedigree (b), above, shows the results of a cross between first cousins both of whom are carriers for the recessive trait, which they inherited from their mothers (who are sisters). A. De Jong/TFSS 2009 Page 8 of 14
Example 3 Sex- linked Recessive Characteristics of a pedigree for a sex- linked recessive trait: Trait does not appear in all generations Trait may appear in offspring of parents who do not express the trait Trait appears to skip generations Trait does not appear equally in both genders o If X- linked, there are clusters of affected males, and few, if any, affected females. Carrier females pass the allele on to sons. Females are only affected if they have an affected father and a carrier mother. o If Y- linked, all males descendants of the P1 father will display the trait. No females will be affected. Queen Victoria s Pedigree Queen Victoria (England) was a carrier for the hemophilia allele. Because of this, and how many children she had (and passed the allele on to) hemophilia is referred to as the Royal Disease. Hemophilia has died out in the current branch of the Royal Family. Image from http://www.biologycorner.com/resources/hemo_pedigree.gif ** Alexei s full name was His Imperial Highness Alexis Nicolaievich, Sovereign Heir Tsarevich, Grand Duke of Russia he was supposed to inherit the throne of Russia. A. De Jong/TFSS 2009 Page 9 of 14
More Variations on a Theme Some dihybrid crosses give unexpected results. There could be several reasons for this. Autosomal Linkage A linkage group is a pair (or group) of genes that are located on the same chromosome Recombinants are offspring that have a different genotype from their parents. With unlinked genes, the recombinants result from independent assortment during meiosis. When genes are linked, recombinants result from crossing over during prophase I. Recombinants will usually have a different phenotype from their parents as well. Example: P1 tall, white (Ttrr) crossed with short, red (ttrr) F1 is ¼ tall, white (Ttrr) ¼ short, red (ttrr) ¼ tall, red (TtRr) ¼ short, white (ttrr) }parental phenotype }recombinant phenotype p = frequency of parental phenotypes r = frequency of recombinant phenotypes p + r = 1 When genes are located close together on the same autosome, the expected numbers of recombinants is not observed. Generally, more parental phenotypes are observed than recombinants. The proportion of recombinants observed indicates the distance between the genes more distance increases the likelihood of crossing over between homologues, which produces recombinants. Example: A dihybrid cross (linked genes) A B a b x a b a b Genotype AaBb aabb Phenotype A B a b Gametes A B a b a b A b (Test Cross) a B A. De Jong/TFSS 2009 Page 10 of 14
Offspring Genotype a b Offspring Type Frequency Phenotype a b parental p/2 a A a A a a a Example: b B b b b B b A B parental p/2 A b recombinant r/2 a B recombinant r/2 In plants, leaf colour and leaf shape are controlled by two linked genes. Leaves of the wild- type plant are red. A recessive mutation causes white leaves. Wild- type leaves are pointed, while a recessive mutation causes them to be smooth. P1 pure white smooth x pure wild type F1 all red & pointed (wild type) When the F1 plants are crossed with pure white & smooth plants (test cross!), the F2 is: 40 white smooth 36 red pointed 10 white pointed 14 red smooth Which of the F1 are recombinants? - white pointed & red smooth What is the recombination frequency? R = red, r = white, P = pointed, p = smooth A. De Jong/TFSS 2009 Page 11 of 14
Using the F1 test cross: R P r p x r p r p Recombination Frequency = # of recombinants total # of offspring = (10 + 14) (10 + 14) + (40 + 36) = 24 100 = 0.24 or 24 cm The genes are 24 cm apart on the chromosome. Polygenic Inheritance Polygenic inheritance is defined as the inheritance of a characteristic that is controlled by more than one gene. Polygenic traits are recognizable by their expression as a graduation of small differences this is called continuous variation, easily observed when you line up a group of individuals by height, for example. There is no set grouping into tall and short, but there is variation between the extremes of very tall to very short and many steps in between. Example 1 Shape of the Comb in Poultry Two genes, pea and rose control the shape of the comb on the head of poultry. Pea and rose are dominant alleles. Birds that inherit the dominant form of the pea gene and the recessive form of the rose gene display the pea comb characteristic. Conversely, birds that inherit the dominant form of the rose gene and the recessive form of the pea gene display the rose comb characteristic. Birds who inherit both dominant genes (i.e. pea and rose) display the walnut comb characteristic. Birds who inherit only the recessive forms of both genes display the single comb characteristic: Image from http://64.78.63.75/samples/05bio104solomonbiology7ch10.pdf A. De Jong/TFSS 2009 Page 12 of 14
If a pure- breeding pea comb bird is crossed with a pure- breeding rose comb bird, the resulting F1 generation all display the walnut comb phenotype: P1 F1 PPrr x pprr PpRr When these F1 birds are crossed, all four phenotypes are observed: F2 PR Pr pr pr PR PPRR PPRr PpRR PpRr Pr PPRr PPrr PpRr PpRr pr PpRR PpRr pprr pprr pr PpRr Pprr pprr pprr 9 Walnut : 3 Pea : 3 Rose : 1 Single Example 2: Human Skin Colour Human skin colour results from varying amounts of the pigment melanin, and is thought to be under the control of at least three independent genes. In each case, the dominant allele results in darker skin pigmentation. (See right) Image from http://64.78.63.75/samples/05bio104solomonbiology7ch10.pdf Other human polygenic traits: hair colour eye colour SLE (lupus) weight intelligence many forms of behaviour predisposition to some disease A. De Jong/TFSS 2009 Page 13 of 14
Karyotyping Sometimes, mistakes occur during meiosis. Non- disjunction is an uneven segregation of chromosomes during gamete formation it results in gametes that have n+1 or n- 1 chromosomes. If these gametes are used for fertilization, the resulting zygote will have more or less than the diploid number (45 or 47 chromosomes in humans). The incidence of non- disjunction increases with age, particularly in women, since baby girls are born with all the eggs they will ever make, halted in prophase I of meiosis. A karyotype is a picture of all the chromosomes in a cell, lined up in order from largest to smallest, with the sex- determining chromosomes in the last position (pair 23 in humans). Two methods of pre- natal diagnosis use karyotyping to determine if a baby has the correct number of chromosomes: Amniocentesis involves taking a sample of amniotic fluid, which will contain cells from the fetus. The cells are cultured in a lab, and then cell division is halted in an early phase. A photograph of the chromosomes is taken, and they are arranged in order by size and banding pattern. Chorionic Villus Sampling is a similar technique, but instead the sample is taken from the chorion. Human Female normal Human Male normal Examples of conditions diagnosable by karyotyping: Down syndrome (trisomy 21, 47 chromosomes per cell) Klinefelter syndrome (XXY male, 47 chromosomes per cell) Turner syndrome (XO female, 45 chromosomes per cell) A. De Jong/TFSS 2009 Page 14 of 14