ANSC20010 Genetics and Biotech Section 2 PDF

ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Section 2: Mendelian Genetics and Extensions of Mendelian Genetics (Chapter 14 in Campbell Biology 12th ed.) 1 Mendelian Genetics – basic transmission genetics How are traits transmitted from parent to offspring? The fundamental pri...

ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Section 2: Mendelian Genetics and Extensions of Mendelian Genetics (Chapter 14 in Campbell Biology 12th ed.) 1 Mendelian Genetics – basic transmission genetics How are traits transmitted from parent to offspring? The fundamental principles of transmission genetics and the particulate nature of heredity were determined by Gregor Mendel in the 1850s and 1860s. Gregor Mendel (1822 – 1884) genetics.org.uk/events/mendels-200th-birthday-garden-party 2 1 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The Augustinian St Thomas's Abbey in Brno, Moravia – now part of the present-day east Czech Republic 3 St Thomas's Abbey is now the Mendel Museum of Masaryk University in Brno https://mendelmuseum.muni.cz/en 4 2 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The earliest known record of applied genetics in a 2800-year-old Assyrian relief from the Northwest Palace of Ashurnasirpal II Assyrian plant breeders recognized male and female organs in plants and carried out artificial pollination. A frieze carved in the 9th century BCE is the oldest known visual record of this kind of genetic experiment. It depicts priests brushing the flowers of female date palms with selected male pollen. By this method of artificial selection, many varieties of dates were produced (differing in taste, size, etc.). Hartwell L.H. et al. (2018) Genetics: From Genes to Genomes, 6th edition, McGraw-Hill Education (page 16). 5 Gregor Mendel – Discovery Channel: Greatest Genetics Discoveries https://youtu.be/yhDLA6ZPQQI (start at 1:57; finish 5:07) 6 3 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendel’s choice of organism for his experiments The plant has a short life cycle. It produces large numbers of offspring. There are many different pea varieties (strains). It is possible to perform experimentally controlled matings using either: – Self-pollination. – Cross-pollination. It is possible to track binary ‘either-or’ characters (e.g., purple flower versus white flower). Lathyrus oleraceus (the domestic pea plant) [previously Pisum sativum] 7 Mendel analysed seven binary ‘either-or’ characters in the pea plant Character Dominant trait Recessive trait Character Dominant trait Recessive trait Brooker, R. J. (2020) Genetics: Analysis & Principles, 7th edition, McGraw-Hill Education (page 22). 8 4 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendel’s experiments with pea plants Mendel began by obtaining “true-breeding” strains of pea plants for each of the seven pairs of traits. Character: a heritable feature that varies among individuals and each character had only two contrasting forms: traits. True-breeding strain: a particular trait appears to be unchanged over several generations in self-fertilising pea plants. True-breeding pea plant strains (varieties) are generated from continual self-fertilisation – pollen and ova from same plant form a zygote. Individual pea strains are highly inbred: they display very little genetic variation from generation to generation for a particular trait. Mendel could also use artificial cross-pollination between different plants whenever he wanted. Important: in modern terminology, each character studied by Mendel is controlled by a single gene. 9 A typical breeding experiment conducted by Mendel: a genetic cross Mendel could cross-fertilise (hybridise) two true-breeding varieties (e.g., purple flowers and white flowers). A monohybrid cross: involved the analysis of only one character, in this case flower colour. The parents are termed the P generation (parental). The hybrid offspring are termed the F1 generation (1st filial* generation). If the F1 self-pollinate this produces an F2 generation (2nd filial generation). Mendel usually performed his experiments across three generations (P, F1 and F2). The F2 generation was particularly important. * Filial is derived from Latin and refers to the relationship between parents and their offspring. 10 5 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendel’s plant breeding experiments: an example of a monohybrid genetic cross Blending inheritance versus particulate inheritance? Two conflicting hypotheses on heredity:  Hypothesis 1: Blending inheritance: o Genetic contributions from the two parents ‘blend’ together in the offspring. o Blending inheritance would be expected to produce uniformity in traits.  Hypothesis 2: Particulate inheritance: o With particulate inheritance, parents pass on discrete “heritable units” (Mendel called them factors, we call them genes) to offspring. o These “heritable units” (factors/genes) retain their own identity in the offspring. Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 270). 11 The (incorrect) 19th century hypothesis of blending inheritance Before the rediscovery of Mendel’s research work in the early 20th century, several scientists including Charles Darwin, considered and explored blending inheritance as a mechanism for the transmission of traits from parents to offspring. Blending inheritance can be considered analogous to ‘mixing paint’ at each generation. The traits of the parents determine the outer bounds of the trait manifested in the offspring on a continuum between the parental extremes. A Scottish Professor of Engineering (Fleeming Jenkin) demonstrated that blending inheritance would rapidly lead to complete uniformity for a biological trait. Note: See Section 5 12 6 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Charles Darwin and blending inheritance: Text from a letter to T.H. Huxley (November 12th, 1857) “I have lately been inclined to speculate very crudely & indistinctly, that propagation by true fertilisation, will turn out to be a sort of mixture & not true fusion, of two distinct individuals, or rather of innumerable individuals, as each parent has its parents & ancestors:— I can understand on no other view the way in which crossed forms go back to so large an extent to ancestral forms.” Charles Darwin (1809–1882) Thomas Henry Huxley (1825–1895) Fleeming Jenkin (1833–1885) 13 Mendel’s monohybrid genetic cross experiments supported the hypothesis of particulate inheritance in pea plants Mendel crossed true-breeding purpleflowered plants and white-flowered plants. The resulting F1 hybrids were allowed to self-pollinate or were crosspollinated with other F1 hybrids. The F2 generation plants were then observed for flower colour. Both purple-flowered and white-flowered plants appeared in the F2 generation, in a ratio of approximately 3:1 (705:224). The “heritable factor” (gene allele) for the recessive trait (white flowers) had not been destroyed, deleted, or “blended” in the F1 generation but was merely masked by the presence of the factor (gene allele) for purple flowers, which is the dominant trait. Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 271). 14 7 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendel’s 1st law: the Law of Segregation From his work on monohybrid crosses Mendel formulated his first law of inheritance. Mendel’s first law ‒ The Law of (allele) Segregation: “In a sexually reproducing organism, the two alleles of a gene controlling a character separate (segregate) into different gametes during gamete production (i.e. meiosis) such that half of the gametes carry one allele and the other half carry the other allele.” www.khanacademy.org/science/ap-biology/heredity/mendelian-genetics-ap/a/the-law-of-segregation 15 Blending inheritance versus particulate inheritance 16 8 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 A colour mixing analogy for blending inheritance (the incorrect model) and particulate inheritance (the correct Mendelian model) Note: the green coloured light obtained here is more analogous to codominance (see later in this section). 17 Mendel’s 1st Law: the Law of Segregation Demonstrate with Mendel_garden.xlsx Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 273). 18 9 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Phenotype versus genotype for Mendel’s flower colour character Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 274). 19 The molecular basis of the simple flower colour trait used by Mendel for his pea plant experiments Note: See Section 4 Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 273). 20 10 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 What is the relationship between genes (and alleles) and chromosomes? Note: See Section 3 Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 294). 21 The results of Mendel’s F1 crosses for seven characters in pea plants Mendel, J. G. (1866). "Versuche über Pflanzenhybriden", Verhandlungen des naturforschenden Vereines in Brünn, Bd. IV für das Jahr, 1865, Abhandlungen: 3–47 Demonstrate with Mendel_garden.xlsx Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 272). 22 11 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Useful genetics terminology A discrete unit of hereditary information: gene. The position of gene on a chromosome: locus (plural, loci). Different versions of a gene: alleles. A diploid organism with a pair of identical alleles for a character is a homozygote and described as homozygous. A diploid organism with pair of different alleles for a character is a heterozygote and described as heterozygous. The physical manifestation of the trait is the phenotype. The genetic composition for that trait is the genotype. 23 Mendel’s Testcross Given a purple-flowered pea plant, we cannot tell if it is homozygous (PP) or heterozygous (Pp) because both genotypes result in the same purple phenotype. To determine the genotype, we can cross this plant with a white-flowered plant (pp), which will make only gametes with the recessive allele (p). The allele in the gamete contributed by the purple-flowered plant of unknown genotype will therefore determine the appearance of the offspring. If all the offspring of the cross have purple flowers, then the purple-flowered mystery plant must be homozygous for the dominant allele (PP). But if both the purple and the white phenotypes appear among the offspring, then the purple-flowered parent must be heterozygous (Pp). Breeding an organism of unknown genotype with a recessive homozygote is called a testcross because it can reveal the genotype of that organism. Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 275). 24 12 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Some deductions from Mendel’s flower colour crossing experiments using modern genetics terms [extra notes] 1. Mendel hypothesised that purple and white flower traits were controlled by “particulate heritable factors”:  These factors were transmitted from parent to offspring through the gametes (pollen and ova [eggs]).  These factors carry hereditary information.  In modern terminology these particulate factors are genes.  NB: In modern terminology, the flower colour character is termed the flower colour phenotype.  In this example, there is a purple flower colour trait and a white flower colour trait. 25 Some deductions from Mendel’s flower colour crossing experiments using modern genetics terms [extra notes] 2. The gene controlling flower colour character existed in two different forms:  Alternative forms of a gene are termed alleles. o The word allele is derived from classical Greek and means “each other”.  Each allele specified one of the traits.  In this case the gene is a flower colour gene for which there are two alleles: o A purple flower allele (P). o A white flower allele (p). 26 13 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Some deductions from Mendel’s flower colour crossing experiments using modern genetics terms [extra notes] 3. Plants carry two alleles for the flower colour character:  The dominant allele masks the effects of the recessive allele in the F1 generation.  Only one copy of the purple allele is required to observe the purple flower trait.  Two copies of the white allele are required to observe the white flower trait.  This explains why the white flower trait disappears in the F1 generation and reappears in the F2 generation. 27 Some deductions from Mendel’s flower colour crossing experiments using modern genetics terms [extra notes] 4. Alternative versions of genes (alleles) account for variation in inherited characters.  For each character, an organism inherits two alleles, one from each parent.  The two alleles are located on different homologous chromosomes. 28 14 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Some deductions from Mendel’s flower colour crossing experiments using modern genetics terms [extra notes] 5. Alternative versions of genes (alleles) account for variation in inherited characters.  If the two alleles differ, then the dominant allele is fully expressed and the recessive allele has no noticeable effect on the organism’s phenotype.  At the cellular level, the two alleles for each character segregate during gamete production.  This led to the formulation of Mendel’s 1st Law: The Law of Segregation (also sometimes called Mendel’s Principle of Segregation) 29 Gregor Mendel and the Principles of Inheritance: Scitable at the Nature Education website https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593 30 15 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendel’s 2nd law: the Law of Independent Assortment Mendel derived his 1st law (the Law of Segregation) from monohybrid crosses. Mendel derived his 2nd law, the Law of Independent Assortment, by following two characters at the same time. He did this with crosses involving two characters (dihybrid crosses). For example, he used a dihybrid cross for these two pea plant characters:  Seed colour: yellow or green (two alleles Y or y).  Seed shape: round or wrinkled (two alleles R or r). Mendel crossed two true-breeding lines: Yellow-Round (YYRR) and GreenWrinkled (yyrr). 31 Mendel’s 2nd law: the Law of Independent Assortment To follow the characters of seed colour and seed shape through the F2 generation, Mendel crossed a true-breeding plant with yellow round seeds and a true-breeding plant with green wrinkled seeds, producing dihybrid F1 plants. Self-pollination of the F1 dihybrids produced the F2 generation. We can ask the question: are the two characters, seed colour and seed shape, transmitted as a package from parent to offspring? Hypothesis 1: the Y and R alleles (and the y and r alleles) always stay together during meiosis. Hypothesis 2: the seed colour and seed shape characters are inherited independently (i.e., the Y and R alleles and the y and r alleles segregate independently into gametes). Mendel tested his seven pea characters in various dihybrid combinations and formulated his 2nd law (the Law of Independent Assortment) based on the results of these experiments. 32 16 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Do the alleles for one character segregate into gametes dependently or independently of the alleles for a different character? Mendel obtained the following F2 results for this dihybrid cross (556 plants in total): F2 plants with yellow seeds.  315 F2 plants with green seeds.  108 F2 plants with yellow wrinkled seeds.  101 F2 plants with green wrinkled seeds.  32 Demonstrate with Mendel_garden.xlsx An approximate phenotypic ratio. 9:3:3:1 Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 276). 33 Mendel’s 2nd law: the Law of Independent Assortment Mendel’s F2 results for the seed colour and shape dihybrid cross: 315 | 108 | 101 | 32 ≈ 9:3:3:1 These results support Hypothesis 2: the two characters are inherited independently. When Mendel examined the seven different pea plant characters in various dihybrid combinations, he always observed an approximate 9:3:3:1 ratio in the F2 generation. The results of Mendel’s dihybrid experiments are the basis for what we now call the Law of Independent Assortment, which states that two or more genes assort independently—that is, each pair of alleles segregates independently of any other pair of alleles—during gamete formation. Note that a 3:1 ratio remains for each character alone: 12 yellow to four green and 12 round to four wrinkled (the segregation is the same as a separate monohybrid cross for each character). 34 17 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 A 3:1 ratio remains for each character examined separately 12 plants that produce yellow seeds (peas) to 4 plants that produce green seeds (peas) 3:1 ratio 12 plants that produce round seeds (peas) to 4 plants that produce wrinkled seeds (peas) 3:1 ratio 35 The chromosomal basis of Mendel’s laws Note: See Section 3 Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 297). 36 18 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The chromosomal basis of Mendel’s laws 37 38 19 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The chromosomal basis of Mendel’s laws Note: See Section 3 39 Probability laws govern Mendelian inheritance Mendel’s laws of segregation and independent assortment reflect the same rules of probability that apply to tossing coins, rolling dice, and drawing cards from a deck. With a normal coin, the chance of tossing heads is ½ [50% or 0.500], and the chance of tossing tails is ½ [50% or 0.500]. The probability of drawing the ace of spades from a 52-card deck is 1/52 [0.0192]. The probabilities of all possible outcomes for an event must add up to 1. With a deck of cards, the chance of picking a card other than the ace of spades is 51/52 [0.9808]. Tossing a coin illustrates an important lesson about probability. For every toss, the probability of heads is ½. The outcome of any particular toss is unaffected by what has happened on previous trials. We refer to phenomena such as coin tosses as independent events. Each toss of a coin, whether done sequentially with one coin or simultaneously with many, is independent of every other toss (c.f., the Gambler’s Fallacy). 40 20 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Probability laws govern Mendelian inheritance The multiplication and addition rules applied to monohybrid crosses:  By the multiplication rule, the probability that two coin tosses will both land heads up is 0.50 × 0.50 = 0.25 [¼].  We can apply this principle to an F1 monohybrid cross (e.g., Rr for the seed shape character). For segregation in a heterozygous plant each gamete produced has a 0.50 [½] chance of carrying either the R allele or the r allele (applies to the Law of Segregation).  According to the addition rule, the probability that any one of two or more mutually exclusive events (one event or the other) will occur is calculated by adding their individual probabilities. This applies in a F1 monohybrid cross because the Rr genotype can be obtained in two different ways. Finally, for a dihybrid cross: like separate coin tosses, the alleles of one gene segregate into gametes independently of another gene’s alleles (the Law of Independent Assortment). 41 Probability laws govern Mendelian inheritance RR = 0.25 [¼] rr = 0.25 [¼] Rr = 0.50 [½] Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 277). 42 21 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Phenotype versus genotype for Mendel’s flower colour character Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 274). 43 How Mendel's pea plants helped us understand genetics https://youtu.be/Mehz7tCxjSE?si=AZoJIIpJcVwXVD0L 44 22 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Mendelian traits in humans During the early 1900s geneticists observe that the inheritance of several traits in sexually-reproducing eukaryotes (including humans) were consistent with Mendel’s observations. 1903: William Curtis Farabee documented brachydactyly (marked shortening of digits) the first Mendelian trait described in humans and showed it had an autosomal dominant pattern of inheritance. William C. Farabee (1865–1925) 45 Many human diseases are caused by mutations in single genes Griffiths A. J. F. et al. (2015) Introduction to Genetic Analysis, 11th edition, W. H. Freeman and Company (page 61). 46 23 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Examples of Mendelian traits in humans Hartwell L.H. et al. (2018) Genetics: From Genes to Genomes, 6th edition, McGraw-Hill Education (page 31). 47 Conventional symbols used for representing human pedigrees Hartl D. L. (2020) Essential Genetics and Genomics, 7th edition, Jones & Bartlett Learning (page 52). 48 24 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Oculocutaneous albinism (OCA) – affects pigmentation in the skin, hair and eyes: a recessive genetic condition in humans OCA in a person of European ancestry An example pedigree for a recessive genetic condition such as OCA OCA in a person of African ancestry Hartl D. L. (2020) Essential Genetics and Genomics, 7th edition, Jones & Bartlett Learning (page 54). 49 Cystic fibrosis (CF) – affects epithelial tissues such as those lining the airways: a recessive genetic condition in humans Cystic fibrosis is caused by mutations in the CF transmembrane conductance regulator gene (CFTR) www.omim.org/entry/219700 50 25 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Sickle cell anaemia – red blood cells are deformed and unable to function properly: a recessive genetic condition in humans Sickle cell anaemia is caused by a mutation in the human beta globin gene (HBB) Note: See Sections 4 and 5 www.omim.org/entry/603903 51 The ability to taste phenylthiocarbamide (PTC) is due to a polymorphism in the TAS2R38 gene (non-tasting is recessive) C/C C/G G/G Can taste PTC ~25% of Europeans Can taste PTC ~50% of Europeans Cannot taste PTC ~25% of Europeans www.omim.org/entry/171200 52 26 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Huntington’s disease – a progressive nerve degeneration disease: a dominant genetic condition in humans www.omim.org/entry/143100 Hartl D. L. (2020) Essential Genetics and Genomics, 7th edition, Jones & Bartlett Learning (page 52). 53 Pseudoachondroplasia, a rare type of dwarfism that shows a dominant pattern of inheritance Seven siblings with pseudoachondroplasiais, which is caused by inactivating mutations in the cartilage oligomeric matrix protein gene (COMP). People with normal stature are genotypically d/d, and the dwarf phenotype is always D/d. Two “doses” of the D allele in the D/D genotype are thought to produce a lethal outcome during embryonic development. www.omim.org/entry/177170 54 27 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Chondrodysplasia (Bulldog dwarfism) in Dexter cattle A type of dwarfism that shows a dominant pattern of inheritance Note: See later in Section 2 for this as an example of lethal alleles www.omia.org/OMIA001271/9913 55 Some Mendelian genetics problems A recessive single gene inherited condition (e.g., cystic fibrosis) occurs when an individual inherits two copies of the recessive allele (a). Heterozygous individuals (with genotype Aa) have only one copy of the a allele and are phenotypically normal (i.e., they do not manifest the condition) but are carriers for the condition. Tom and Mary are a couple planning to have their first child. Both Tom and Mary are carriers (Aa) for the condition. 1. Calculate the probability that Tom and Mary’s first child will be affected by the condition. 2. If Tom and Mary have two children what is the probability that both children will be affected by the condition? 3. If Tom and Mary have two children, what is the probability that both children will not be affected by the condition? 4. If Tom and Mary have two children what is the probability that only one of their children will be affected by the condition? 56 28 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Extensions of Mendelian genetics Flower colour in the snapdragon plant (Antirrhinum majus) is an example of incomplete dominance – an extension of simple Mendelian inheritance. 57 Mendel’s experiments had a very simple genetic basis Each character is controlled by one gene with two alleles (one dominant and one recessive). A very simple relationship exists between genotype and phenotype, which led to the formulation of Mendel’s two laws of heredity:  The Law of (allele) Segregation.  The Law Assortment. of Independent Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 272). 58 29 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The relationship between genotype and phenotype is rarely as simple as Mendel’s pea plant characters For nearly all biological organisms the relationship between genotype and phenotype is usually relatively complicated. Most biological characters are controlled by the interaction of more than one gene and may also be influenced by environmental factors. Also, while alleles are transmitted from parent to offspring according to Mendelian principles, the alleles often do not display the clear-cut dominant/recessive relationship observed by Mendel. However, it is important to keep in mind that the concept of particulate inheritance that underpins Mendel’s basic principles still applies for more complex biological characters. 59 Complicated relationships that may be present between genotype and phenotype Lethal alleles Relationship between dominance and recessivity Multiple alleles Genotype (at a single locus) Other genes (epistasis) Environmental factors Phenotype [NB: if a gene affects multiple phenotypes – pleiotropy] 60 30 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Some patterns of inheritance that extend the simple rules that Mendel discovered in pea plants 1. Incomplete dominance:  The phenotype of a heterozygote is distinct from and often intermediate to the phenotype of either homozygote.  Example: flower colour in snapdragons. 2. Codominance:  The phenotypic effect of both alleles is evident in the heterozygote.  Examples: the MN and AB blood groups in humans; roan coat colour in cattle. 3. Multiple alleles at a single gene (present in a population of organisms):  Diploid individuals carry only two alleles for a gene; however, there are more than two alleles for a particular gene present in a population.  Example: the ABO blood group system in humans. 61 Some patterns of inheritance that extend the simple rules that Mendel discovered in pea plants 4. 5. 6. Lethal alleles:  Individuals with two lethal alleles will not survive.  Examples include the Overo Lethal White Foal Syndrome (OLWFS) in horses produced by two overo parents and Bulldog Calf syndrome in Dexter cattle.  A de novo (new mutation) ‘dominant’ allele can also produce lethality. Pleiotropy:  The genotype at a genetic locus affects more than one phenotypic outcome.  A good example is the polled intersex syndrome (PIS) phenotype in domestic goats (two different characters/phenotypes controlled by the polled gene). Epistasis:  A gene alters the phenotypic expression of another gene at a different genetic locus.  A good example is the coat colour character in Labrador dogs. 62 31 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Some patterns of inheritance that extend the simple rules that Mendel discovered in pea plants 7. 8. Quantitative characters/traits:  Quantitative, complex, polygenic, or multifactorial traits (N.B., all four terms mean the same thing) are determined by genomic variation at many genes, genomic regulatory elements (GREs), and multiple environmental factors.  This type of character/trait is extremely important for plant and animal agriculture.  Good examples include human height/stature; human weight; human body mass index (BMI); milk yield in dairy cattle; fleece weight in sheep; backfat thickness in pigs; feed conversion efficiency in broiler chickens; yield per hectare for wheat or maize; and fungal disease resistance in tomatoes. Variation in the expression of simple genetic characters due to environmental effects:  We can also observe relatively simple monogenic or oligogenic characters that are affected by environmental variation. 63 The relationship between dominance and recessivity A spectrum of dominance/recessivity relationships can exist Incomplete dominance (e.g., flower colour in snapdragon plants) Complete dominance Codominance Round seed vs. wrinkled seed shape in pea plants Roan coat colour (cattle) MN blood group (humans) AB blood group (humans) 64 32 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The relationship between genotype and phenotype is rarely as simple as Mendel’s pea plant characters Can range from complete dominance through degrees of incomplete dominance to codominance. Note: incomplete dominance is not codominance. Dominance/recessivity relationships reflect the molecular mechanisms (at the DNA and protein level) by which specific alleles determine the phenotypic trait for the character. Dominance/recessivity does not involve the subjugation of one allele by another at the molecular level. Dominance/recessivity does not determine the relative abundance of alleles in a population. 65 What exactly does the term dominant allele mean? Dominant allele: for a particular monogenic character, the dominant allele is the allele that is fully expressed in a heterozygous organism. Different gene alleles are generated when the DNA sequence of a gene is altered by mutation (often very small differences can affect phenotypic outcomes). The purple and white flower alleles described by Mendel represent two different DNA sequence variations at the flower colour gene locus. Remember: an allele is not dominant because it “subdues” a recessive allele. The protein products of dominant and recessive alleles in an organism with a heterozygous genotype do not normally directly interact at the molecular level. It is the “pathway” from genotype to phenotype where dominance and recessivity come into play. 66 33 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 What exactly does the term dominant allele mean? The terms dominance and recessivity, originally codified by Gregor Mendel, are not strictly speaking intrinsic properties of genes or alleles but describe, in diploid organisms, the pattern of occurrence of a phenotypic trait with respect to the possible combinations of two alleles. If the trait is present in the heterozygote, it is said to be dominant or semidominant, and if it is present only in one of the homozygotes, it is recessive. In contemporary genetics, these terms are frequently used in a different but useful way to describe a property of the variant or mutant allele itself in relation to the normal, wild-type state; this context is very helpful for understanding the molecular mechanisms by which mutations lead to disease. Practical applications include elucidation of genotype–phenotype relationships, structure–function studies of proteins and prediction of patterns of segregation of phenotypes to offspring in contexts such as selective breeding and genetic counselling. Wilke (2018) Dominance and Recessivity; Encyclopaedia of Life Sciences [online] 67 A molecular explanation of a dominance/recessivity relationship: Mendel’s pea shape character RR or Rr rr 68 34 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Complete dominance: the biochemical basis of the round and wrinkled phenotypes observed for the seed shape character Mendel’s pea plant breeding experiments involved characters where one of the traits displayed complete dominance. For example: for the seed shape character, plants with the heterozygous genotype (Rr) show that the round seed allele (R allele) is dominant to the wrinkled seed allele (r allele).  At the biochemical level, the R allele of the pea shape gene (the starch branching enzyme 1 gene – SBE1) specifies the enzyme Sbe1, which converts unbranched starch (amylose) to branched starch (amylopectin). The r allele of the SBE1 gene is nonfunctional and does not produce the Sbe1 enzyme.  Seed wrinkling happens in rr plants because the amylose breaks down leading to elevated levels of simple sugars (glucose, sucrose and fructose), which initially results in higher water content in immature seeds due to increased osmotic pressure. Higher water content leads to swelling, which produces wrinkled seeds (peas) when they mature and dry out.  Pea plants with a functional (R) and non-functional copy (r) of SBE1 produce enough enzyme to prevent mature seeds wrinkling. Therefore, Rr heterozygotes manifest the dominant phenotype. 69 Disruption of the Pisum sativum SBE1 gene by an 800 bp insertion leads to the wrinkled phenotype in the rr genotype The r allele of the SBE1 gene is disrupted by an 800 bp (0.8 kb) insertion of DNA that interrupts the protein-coding sequence of the gene, producing a non-functional enzyme. Hartwell L.H. et al. (2018) Genetics: From Genes to Genomes, 6th edition, McGraw-Hill Education (page 29). 70 35 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The molecular basis of the simple flower colour trait used by Mendel for his pea plant experiments Note: See Section 4 Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 273). 71 Dominant does not mean more frequent in the population Approximately one in 400 babies are born with extra digits – polydactyly. The allele for polydactyly is dominant to the allele for the normal five digits. Therefore approximately 399/400 (99.75%) people are recessive homozygotes. Therefore, the recessive allele is much more frequent than the dominant allele. Another example: in commercial cultivated varieties of pea plants, the recessive green seed colour allele (y) has become fixed (has a frequency of 1.0 [100%] in each cultivated variety). 72 36 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Polydactyly: a dominant trait present at low frequencies in human populations Anne Boleyn 1501‒1536 73 The green y allele (and yy genotype) is fixed (present at a frequency of 100%) in commercial pea plant varieties 74 37 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Incomplete dominance Incomplete dominance: for an organism with the heterozygous genotype, one allele is not completely dominant over the other allele. The heterozygote has an intermediate phenotype compared to the two homozygous genotypes (N.B. this is not blending inheritance). Flower colour in the snapdragon plant (Antirrhinum majus) is an example of incomplete dominance. 75 Incomplete dominance in the snapdragon plant Phenotype Genotype Amount of gene product CR CR 2× CR CW 1× CW CW 0 1:2:1 ratio Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 279). 76 38 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Incomplete dominance in the snapdragon plant The F1 pink heterozygous phenotype in the cross is not due to blending inheritance (i.e., the CR and the CW alleles have not combined to create a ‘pink allele’). There is segregation of the red and white alleles in the gametes produced by pink flowered plants during meiotic cell division (in the snapdragon, the flower colour character is heritable and particulate). However, there is a dosage effect in the amount of flower pigment produced (unlike the purple/white flower colour character examined by Mendel in pea plants). 77 Codominance Codominance: codominance occurs in a monogenic character when both phenotypes separately manifest in heterozygous organisms. The heterozygote exhibits the phenotypes for both homozygotes simultaneously. Codominance is often observed in human blood group characters.  The human MN blood group system.  The human ABO blood group system. 78 39 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 An example of codominance: the human MN blood group system There are three different MN blood groups: M, N and MN. The MN blood group system is controlled by a single gene with two alleles (LM and LN) that encode antigens expressed on the surface of red blood cells.  M blood group: only the M-type antigen is present.  N blood group: only the N-type antigen is present.  MN blood group: both antigens are present. N.B. The MN phenotype is not intermediate between M and N. Diagnosis of human MN blood groups is performed by a reaction with antisera. 79 An example of codominance: the human MN blood group system Genotype Blood type (antigen present) Reactions with anti-sera Anti-M sera LMLM M LMLN M and N LNLN N Anti-N sera N.B. The “L” is a tribute to Karl Landsteiner (discoverer of blood-groups) 80 40 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 An example of codominance in livestock: roan coat colour in shorthorn cattle If purebred red shorthorn cattle are crossed with purebred white shorthorn cattle, a uniform F1 is produced with intermingled white and red hairs (roan coat colour). N.B., this is not incomplete dominance: both phenotypes are still manifested (white and red hairs - not pink hairs!). The causative mutation for the roan coat colour trait has been identified: a change to the codon encoding amino acid 193 (Ala  Asp) in the bovine KIT ligand gene (KITLG) on bovine chromosome 5 (BTA5). www.omia.org/OMIA001216/9913 81 An example of codominance in livestock: Roan coat colour in shorthorn cattle CRCR red coat P generation CWCW white coat CR CW CRCW roan coat F1 generation CR ova CW F2 generation CR CW CR sperm CW 1:2:1 ratio 82 41 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 An example of multiple alleles at the same gene locus: the ABO blood group system in humans There are four possible ABO blood group phenotypes: blood groups A, B, AB, or O. Similarly, to the MN system, A and B antigens can be present on the surface of red blood cells (N.B., the MN and ABO blood group systems are controlled by different genes). The ABO blood group system is controlled by a gene with three alleles present in human populations:  The A IA allele expresses the A antigen.  The B IB allele expresses the B antigen.  The O i allele expresses neither antigen (this version of the gene is nonfunctional). Matching compatible blood groups is critical for blood transfusions. If the donor’s blood has a factor (A or B antigen) that is foreign to the recipient, host antibodies will cause the donated red blood cells to agglutinate. 83 An example of multiple alleles at the same gene locus: the ABO blood group system in humans 84 42 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 An example of multiple alleles at the same gene locus: the ABO blood group system in humans  =  no clumping = Clumping (not suitable for transfusion) (suitable for transfusion) Recipient’s blood group information Donor’s blood group information Phenotype (blood group) Genotypes Antigens on RBC surface Antibodies in blood serum O A B AB O ii None Anti-A Anti-B     A IAIA or IAi A antigen Anti-B     B IBIB or IBi B antigen Anti-A     AB IAIB A and B antigens None     85 The molecular basis of the agglutination test for ABO blood groups Clumping of A cells by anti-A antibodies No reaction of A cells with anti-B antibodies Unaided eye Microscope Schematic molecular view Red blood cell surface antigen (A antigen) Anti-A antibody binds to A antigen Anti-B antibody will not bind to A antigen 86 43 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 A lethal allele: the overo lethal white foal syndrome (OLWFS) Certain gene alleles are fatal in the homozygous condition and fatality happens during gestation, at birth, or between birth and puberty. A DNA sequence polymorphism at the equine endothelin receptor type B gene (EDNRB) on equine chromosome 17 (ECA17) determines if a horse will be solid, mottled (overo) or white (N.B., other coat colours and patterns are specified by different genes). The homozygous genotype that produces a white coat (WW) is lethal. The heterozygous genotype (Ww) is overo (mottled), and the other homozygous genotype (ww) is normal (produces a solid coat colour). Note: the lethal allele is considered dominant (W) because the heterozygote manifests the overo coat (it is actually a form of semi-dominance). The condition is also termed megacolon in horses and there is a similar genetic disorder in humans termed Hirschsprung disease. www.omia.org/OMIA000629/9796 87 A horse with the overo (mottled) phenotype (Ww) 88 44 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 A lethal allele: the overo lethal white foal syndrome (OLWFS) Parents (Overo) Ww w ww W Ww w W Ww w w W Ww W WW 1:2 phenotypic ratio (viable offspring only) 1:2:1 phenotypic ratio for all actual progeny (including those that die at birth or soon afterwards) 89 A foal with OLWFS and a heterozygous overo mare: the foal has a non-functional colon and will die within a few days https://youtu.be/YJ3-9KvoB-g 90 45 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Chondrodysplasia (bulldog dwarfism) in Dexter cattle: an example of a lethal allele in cattle A lethal allele present in the Dexter cattle population causes bulldog calf syndrome in the homozygous condition (two copies of the lethal allele). Affected bulldog calves are stillborn during the latter stages of pregnancy with dead foetuses normally expelled by a natural abortion around the 7th month of gestation. Animals with the heterozygous genotype show a milder form of dwarfism (chondrodysplasia), most noticeably shorter legs. Two different causative mutations for Bulldog dwarfism have been identified in the aggrecan gene (ACAN) on bovine chromosome 21 (BTA21). www.omia.org/OMIA001271/9913 91 Chondrodysplasia (bulldog dwarfism) in Dexter cattle: an example of a lethal allele in cattle www.omia.org/OMIA001271/9913 92 46 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Chondrodysplasia (bulldog dwarfism) in Dexter cattle: an example of a lethal allele in cattle A heterozygous animal that has a copy of the normal allele and a copy of the lethal allele (manifests as a dwarf phenotype) A stillborn calf homozygous for the lethal allele 93 Pleiotropy: an example is horn development and the polled intersex syndrome (PIS) phenotype in goats The term “pleiotropy” is derived from classical Greek: pleio (“many”) and tropic (“affecting”). The term intersexual is used when an animal has genitalia or secondary sexual characteristics suggesting both female and male features. Intersexuality occurs with a higher frequency in goats than in many other mammals. In goats, intersexuality is often due to a recessive trait associated with the dominant allele for the absence of horns (polled). The genetic basis of this common intersex phenotype in goats (polled intersex syndrome – PIS) is a complex structural genomic polymorphism affecting the potassium inwardly rectifying channel subfamily J member 15 gene (KCNJ15) and ETS transcription factor ERG gene (ERG) on Capra hircus chromosome 1 (CHI1). www.omia.org/OMIA000483/9925 94 47 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Pleiotropy: an example is horn development and the polled intersex syndrome (PIS) phenotype in goats 95 Pleiotropy: an example is horn development and the polled intersex syndrome (PIS) phenotype in goats × Parents Pp Can be less fertile Pp PP ? Intersex - PIS Pp Male progeny 3:1 Female Progeny 1:2:1 Pp pp 96 48 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Pleiotropy: an example is horn development and the polled intersex syndrome (PIS) phenotype in goats Male polled (Pp) ? Female intersex (PP) Female polled (Pp) Simon R. et al. (2020) New genomic features of the polled intersex syndrome variant in goats unraveled by long-read whole-genome sequencing. Anim. Genet. 51, 439-48. 97 Epistasis: an example is certain coat colour polymorphisms in particular mammals The term epistasis is derived from classical Greek and basically means “stopping” or “stands upon” in English. Epistasis occurs when a gene at one locus alters the phenotypic expression of a gene at a second locus. A good example is coat colour in Labrador dogs: two genes are involved, and each gene has two alleles:  Gene 1 (coat colour):  The black coat colour allele (B) is dominant to a brown coat colour allele (b).  Gene 2 (pigment deposition):  The deposition allele (E) is dominant to a non-deposition allele (e).  Black or brown coat development is determined by the genotype at the pigment deposition gene ( so there are two genes affecting a single character).  The black or brown coat will not appear if the individual is homozygous for the non-deposition allele (ee) and these animals are always cream-coloured (no coat pigment). 98 49 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Epistasis in Labrador dogs Urry L. A. et al. (2020) Campbell Biology, 12th edition, Pearson Education, Inc. (page 281). 99 Quantitative, complex, polygenic, or multifactorial traits are influenced by multiple genes and environmental factors Quantitative, complex, polygenic, or multifactorial traits (N.B., all four terms mean the same thing) are determined by genomic variation at many genes, genomic regulatory elements (GREs), and multiple environmental factors. This type of character/trait is extremely important for plant and animal agriculture. Good examples include human height/stature; human weight; human body mass index (BMI); milk yield in dairy cattle; fleece weight in sheep; backfat thickness in pigs; feed conversion efficiency in broiler chickens; yield per hectare for wheat or maize; and fungal disease resistance in tomatoes. Understanding the genetic architecture of complex traits is a key aim of quantitative genetics and its application to animal and plant breeding. Estimating the proportion of variation for a trait in a population due to genetic factors allows us to determine the heritability for a polygenic trait. 100 50 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Complex (polygenic) traits tend to follow a normal (Gaussian) distribution Examples of mathematically generated normal (Gaussian) distributions 101 A “living histogram” showing the distribution of height, a complex (polygenic, quantitative) trait in humans Genetics students at the University of Connecticut in Storrs, who have helpfully arranged themselves by height to form a “living histogram.” Note: adult height is generally highly heritable for human populations in developed countries (narrow sense heritability [h2] ≈ 0.70–0.80). Hartl D. L. (2020) Essential Genetics and Genomics, 7th edition, Jones & Bartlett Learning (page 480). 102 51 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Milk yield in dairy cattle: an example of a complex (polygenic) trait that follows a normal (Gaussian) distribution Number of animals Heritability (h2) for milk yield ≈ 0.30–0.40 Milk yield (binned) kg/annum [for 1000 hypothetical North American Holstein dairy cattle] 103 Fleece weight in sheep: an example of a complex (polygenic) trait that follows a normal (Gaussian) distribution Number of animals Heritability (h2) for fleece weight ≈ 0.25–0.60 Fleece weight (binned) kg [for 1000 hypothetical Merino wool sheep] 104 52 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Variation in a complex trait for a particular population can be separated into genetic and environmental components The distribution of binned phenotypes determined by the segregation of 3 and 30 independent genes. Both distributions are approximated by the same normal distribution (black curve). Segregation of three independent genes affecting a complex trait. Each uppercase allele in a genotype contributes one unit to the phenotype. Even in the absence of environmental variation, the distribution of phenotypes, by itself, provides no information about the number of genes influencing a trait and no information about the dominance relations of the alleles. The distribution of a trait in a population provides no information about the relative importance of genotype and environment. Variation in the trait can be entirely genetic, entirely environmental, or a combination of both influences. Hartl D. L. (2020) Essential Genetics and Genomics, 7th edition, Jones & Bartlett Learning (pages 483-484). 105 United States dairy production per cow (kg/year) 1925 – 2021 11,000 10,000 9,000 8,000 Introduction of genomic selection 7,000 6,000 5,000 Introduction of scientific breeding and AI (frozen sperm) 4,000 3,000 2,000 1,000 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Source: USDA National Agricultural Statistics Service: www.nass.usda.gov 106 53 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 Artificial selection in broiler chickens over 60 years (older lines: selection halted in 1957 and 1978) Zuidhof M.J. et al. (2014) Growth, efficiency, and yield of commercial broilers from 1957, 1978, and 2005. Poult. Sci. 93, 2970-82. 107 Two different chicken lines at eight weeks of age This illustrates size-based breeding by geneticist Paul Siegel at Virginia Tech. “We’re using artificial selection as a tool to look at natural selection. We just accelerate it.” www.nationalgeographic.com/magazine/2011/03/animal-domestication 108 54 ANSC20010 Genetics and Biotech: Section 2 Spring Trimester, 2023-24 The effect of environment on phenotype: variation in the expression of simple genetic characters due to environmental effects We can also observe relatively simple monogenic or oligogenic characters that are affected by environmental variation in a systematic way. Some examples are shown below. The acidity and free aluminium content of the soil affect the colour of hydrangea (Hydrangea spp.) flowers, which range from pink (basic soil) to blue-violet (acidic soil). Free aluminium is necessary for bluer colours. Arctic foxes (Vulpes lagopus), have completely white dense fluffy winter fur, whereas their summer fur is much thinner and mostly brown with lighter ventral sides. 109 55