Ch 4 Mendelian Inheritance (1) PDF

Because learning changes everything. ® Chapter 4 Extensions of Mendelian Inheritance © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McG...

Because learning changes everything. ® Chapter 4 Extensions of Mendelian Inheritance © 2021 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.  Topics Different types of alleles and how they cause disease Effect of the environment on gene expression Incomplete dominance, overdominance, and codominance Sex-linked inheritance Sex-influenced and sex-limited inheritance Lethal alleles Gene interactions https://www.biologyonline.com/dictionary/codominance © McGraw Hill 2  Simple Mendelian Inheritance Mendelian inheritance describes inheritance patterns that obey two laws Law of segregation Law of independent assortment Simple Mendelian inheritance involves A single gene with two different alleles Alleles display a simple dominant/recessive relationship  Many traits deviate from a simple dominant/recessive relationship  They still obey Mendelian laws, but they are more complex © McGraw Hill 3  Dominant and Recessive Alleles Prevalent alleles in a population = wild-type alleles Encode proteins that Function normally Are made in the proper amounts Genetic Polymorphism can produce more than one wild- type in large populations © McGraw Hill 4  Dominant and Recessive Alleles Mutant alleles = alleles that have been altered by mutation Often defective in their ability to express a functional protein Rare in natural populations Often inherited in a recessive fashion © McGraw Hill 5  Dominant and Recessive Alleles Simple dominant/recessive relationship  the recessive allele does not affect the phenotype of the heterozygote Why not? Two possible explanations: 50% of the normal protein is enough Heterozygote may produce > 50% of the functional protein The normal gene is “up-regulated” to compensate for the lack of function of the defective allele © McGraw Hill 6  A Comparison of Protein Levels Among Genotypes Dominant (functional) allele: P (purple) Recessive (defective) allele: p (white) Genotype: Amount of functional protein P PP: 100% Pp: 50% pp: 0% PP-Purple Pp-Purple pp-White Phenotype: Simple dominant/recessive relationship Access the text alternative for slide images. © McGraw Hill 7  Genetic Diseases Are Usually Caused by Mutant Alleles Many human genetic diseases  recessive allele contains a mutation. Prevents the allele from producing a fully functional protein *Individuals who exhibit the disease are either homozygous for a recessive allele or hemizygous (for X-linked genes in human males). The disease symptoms result from a defect in the amount or function of the normal protein. https://owlcation.com/stem/Genetic-Disorders-Phenylketonuria © McGraw Hill 8  Examples of Recessive Human Diseases Protein That Is Produced by Disease Description the Normal Gene* Phenylketonuria Phenylalanine hydroxylase Inability to metabolize phenylalanine. The disease can be prevented by following a phenylalanine-free diet. If the diet is not followed early in life, the result can be severe mental impairment and physical degeneration. Albinism Tyrosinase Lack of pigmentation in the skin, eyes, and hair. Tay-Sachs disease Hexosaminidase A Defect in lipid metabolism. Leads to paralysis, blindness, and early death. Sandhoff disease Hexosaminidase B Defect in lipid metabolism. Muscle weakness in infancy, early blindness, and progressive mental and motor deterioration. Cystic fibrosis Chloride transporter Inability to regulate ion balance across epithelial cells. Leads to production of thick mucus and results in chronic lung infections, poor weight gain, and organ malfunctions Lesch-Nyhan Hypoxanthine-guanine Inability to metabolize purines, which are bases syndrome phosphoribosyl transferase found in DNA and RNA. Leads to self-mutilation behavior, poor motor skills, and usually mental impairment and kidney failure. © McGraw Hill 9  Dominant Mutants Dominant Mutants are much less common than recessive Three explanations for most dominant mutations Gain-of-function Protein encoded by the mutant gene is changed so it gains a new or abnormal function Dominant-negative Protein encoded by the mutant gene acts antagonistically to the normal protein Haploinsufficiency mutant is loss-of-function heterozygote does not make enough product to give the wild type phenotype © McGraw Hill 10  Incomplete Penetrance In some instances, a dominant allele does not influence the outcome of a trait in a heterozygote individual Example: Polydactyly Autosomal dominant trait Affected individuals have additional fingers and/or toes A single copy of the polydactyly allele is usually sufficient to cause this condition In some cases, however, individuals carry the dominant allele but do not exhibit the trait © McGraw Hill 11  Incomplete Penetrance © McGraw Hill 12  Incomplete Penetrance A dominant allele does not always “penetrate” into the phenotype of the individual The measure of penetrance is described at the population level If 60% of heterozygotes carrying a dominant allele exhibit the trait, the trait is 60% penetrant Note: In any particular individual, the trait is either present or not © McGraw Hill 13  Expressivity Expressivity is the degree to which a trait is expressed In polydactyly, the number of digits can vary A person with several extra digits  high expressivity A person with a single extra digit  low expressivity https://boneandspine.com/polydactyly/ https://www.nejm.org/doi/full/10.1056/NEJMicm1100857?query=recirc_inIssue_bottom_article © McGraw Hill 14  Expressivity and Incomplete Penetrance Why?? In most cases, the range of phenotypes is thought to be due to influences of the Environment Other ‘modifier’ genes © McGraw Hill 15  Environmental Effects on Gene Expression Environmental conditions may impact phenotype Some animals like the arctic fox change coat color Grayish brown in summer, white in winter This is an example of a temperature-sensitive allele Humans affected by phenylketonuria (PKU) are unable to metabolize phenylalanine Symptoms include mental impairment, foul-smelling urine When detected early, individuals can be fed a restricted diet essentially free of phenylalanine and remain symptom free © McGraw Hill 16  Environmental Effects - Norm of Reaction Geneticists often examine a range of conditions when studying the effect of environment on phenotype This allows them to see the norm of reaction of the environmental influence Example: Facet number in eyes of fruit flies Access the text alternative for slide images. © McGraw Hill (right): ©Tomatito/Shutterstock 17  Incomplete Dominance, Overdominance, and Codominance Incomplete Dominance Heterozygote exhibits a phenotype that is intermediate between the corresponding homozygotes Example: Flower color in the four o’clock plant Two alleles CR = wild-type allele for red flower color CW = allele for white flower color © McGraw Hill 18  Incomplete Dominance In F1: 50% of the CR protein is not sufficient to produce the red phenotype In F2: 1:2:1 phenotypic ratio NOT the 3:1 ratio observed in simple Mendelian inheritance Access the text alternative for slide images. © McGraw Hill 19  Phenotype Comparison tra it is ly th e r a mplete In pea plants, Whe or inco end on in a nt y d ep is d o m m a tra it RR and Rr - round peas m in a nt ly the do los e o w c m i n ed rr - wrinkled peas h exa Microscopic examination Genotype: Amount of functional (starch-producing) protein RR: 100% Rr: 50% Rr: 0% © McGraw Hill 20  Phenotype Comparison Phenotype: With unaided eye (simple dominant/recessive relationship) With microscope (incomplete dominance) Round Round Wrinkled Heterozygotes look round, but they only have half the amount of starch found in homozygous dominants Access the text alternative for slide images. © McGraw Hill 21  Overdominance Heterozygote has greater reproductive success compared to both homozygotes Heterozygote advantage Example: Sickle-cell disease Autosomal recessive disorder Affected individuals produce abnormal form of hemoglobin Two alleles HbA  Encodes the normal hemoglobin, hemoglobin A HbS  Encodes the abnormal hemoglobin, hemoglobin S © McGraw Hill 22  Overdominance HbSHbS individuals have red blood cells that deform into a sickle shape under conditions of low oxygen tension This has two major ramifications Shortens the life span of the red blood cells Anemia results Odd-shaped cells clump Partial or complete blocks in capillary circulation Thus, affected individuals tend to have a shorter life span © McGraw Hill 23  Inheritance of Sickle Cell Disease (a) Normal red blood cell (b) Sickled red blood cell © McGraw Hill (a): © Mary Martin/Science Source; (b): © Science Source 24  The Hbs Allele Is Found at a Fairly High Frequency in Parts of Africa Where Malaria Is Found Malaria is caused by a protozoan, Plasmodium This parasite undergoes its life cycle in two main parts One inside the Anopheles mosquito The other inside red blood cells Red blood cells of heterozygotes, are likely to rupture when infected by Plasmodium This prevents the propagation of the parasite © McGraw Hill 25  Inheritance of Sickle Cell Disease 2 HbAHbS individuals have an “advantage” over HbSHbS, because they do not suffer from sickle cell disease HbAHbA, because they are more resistant to malaria Access the text alternative for slide images. © McGraw Hill 26  Explanations for Overdominance Two alleles produce slightly different proteins  two protein variants produce a favorable phenotype in the heterozygote Three possible explanations for overdominance at the molecular/cellular level Disease resistance Homodimer formation Variation in functional activity © McGraw Hill 27  1. Disease Resistance Examples: Tay-Sachs disease and tuberculosis PKU and fungal toxins © McGraw Hill 28  2. Homodimer Formation For some proteins, the A1A2 homodimer may have better functional activity Gives the heterozygote an advantage The homozygotes that are A1A1 or A2A2 will make homodimers that are A1A1 and A2A2, respectively. The A1A2 heterozygote can make A1A1 and A2A2 and can also make A1A2 homodimers, which may have better functional activity. © McGraw Hill 29  3. Variation in Functional Activity 27° to 32° Celsius (optimum 30° to 37° Celsius (optimum temperature range) temperature range) A heterozygote, E1E2, would produce both enzymes and have a broader temperature range (that is, 27° to 37° Celsius) in which the enzyme would function. Advantage – a combination of both enzymes function over a wider temperature range than either E1E1 or E2E2 alone © McGraw Hill 30  Multiple Alleles Many genes have multiple alleles Commonly found within natural populations Typically three or more different alleles Only two alleles in one individual Example: the ABO blood group © McGraw Hill 31  Multiple Alleles Blood type is determined by the type of antigen present on the surface of red blood cells Antigens are substances that are recognized by antibodies produced by the immune system There are three different alleles that determine which antigen(s) are present on the surface of red blood cells Allele IA, produces antigen A Allele IB, produces antigen B Allele i, does not produce either antigen © McGraw Hill 32  Codominance: ABO Blood Types 1 Allele i is recessive to both IA and IB Alleles IA and IB are codominant They are both expressed in a heterozygous individual Access the text alternative for slide images. © McGraw Hill 33  Genes on Sex Chromosomes Many species have males and females that differ in their sex chromosome composition Certain traits are governed by genes on the sex chromosomes A pedigree for an X-linked disease shows that it is mostly males that are affected with their mothers as carriers © McGraw Hill 34  Pedigree for Duchenne Muscular Dystrophy Access the text alternative for slide images. © McGraw Hill 35  Examples of X-linked Dystrophy Inheritance Patterns Access the text alternative for slide images. © McGraw Hill 36  Sex Chromosomes and Traits Sex-linked genes are those found on one of the two types of sex chromosomes, but not both X-linked Hemizygous in males Only one copy Males are more likely to be affected Y-linked Relatively few genes in humans Referred to as holandric genes Transmitted only from father to son © McGraw Hill 37  Sex Chromosomes and Traits Pseudoautosomal inheritance refers to the very few genes found on both X and Y chromosomes Found in homologous regions needed for chromosome pairing Access the text alternative for slide images. © McGraw Hill 38  Sex-influenced and Sex-limited Inheritance Sex-influenced Inheritance Traits where an allele is dominant in one sex but recessive in the opposite sex Sex influence is a phenomenon of heterozygotes Sex-influenced does not mean sex-linked Sex-influenced traits are autosomal Scur formation © McGraw Hill 39  Sex-influenced Inheritance Example: Scurs (hornlike growth) in cattle Caused by an autosomal gene Allele Sc is dominant in males, but recessive in females Genotype Phenotype in Males Phenotype in Females ScSc Scurs Scurs Scsc Scurs No scurs (hornless) scsc No scurs No scurs © McGraw Hill 40  Sex-limited Inheritance Traits that occur in only one of the two sexes Genes are controlled by sex hormones or the sexual development pathway For example: in humans Ovary development is limited to females Testes growth is limited to males For example: in birds Males have more ornate plumage © McGraw Hill 41  Lethal Alleles Lethal allele = has the potential to cause death typically the result of mutations in essential genes usually recessive Essential genes = required for survival The absence of their protein product leads to a lethal phenotype ~ one-third of all genes are essential Nonessential genes are those not absolutely required for survival © McGraw Hill 42  Example of Manx Inheritance Patterns A lethal allele may produce ratios that seemingly deviate from Mendelian ratios Dominant mutation that affects the spine  short tail © McGraw Hill 43  Conditional Lethal Alleles & Semilethal Alleles Conditional lethal alleles may kill an organism only when certain environmental conditions prevail Temperature-sensitive (ts) lethals A developing Drosophila larva may be killed at 30° Celsius But it will survive if grown at 22° Celsius (permissive temperature) Typically caused by mutations that alter structure of the protein at the nonpermissive temperature Semilethal alleles kill some individuals in a population, but not all of them Environmental factors and other genes may help prevent the detrimental effects of semilethal genes © McGraw Hill 44  Pleiotropy Multiple effects of a single gene on the phenotype = pleiotropy Can be caused because The gene product can affect cell function in more than one way The gene may be expressed in different cell types The gene may be expressed at different stages of development © McGraw Hill 45  Pleiotropic Effects Example: Cystic fibrosis Functional (wild-type) allele encodes the cystic fibrosis transmembrane conductance regulator (CFTR) Regulates ionic balance by transporting Cl- ions Mutant does not transport Chloride effectively In lungs, this causes very thick mucus On the skin, causes salty sweat Poor weight gain due to blockages in tubes that carry digestive enzymes Defect in CFTR can have multiple effects © McGraw Hill 46  Gene Interactions Two or more different genes influence the outcome of a single trait Essentially all traits are affected by contributions of many genes Morphological traits such as height weight and pigmentation are affected by many different genes in combination with environmental factors © McGraw Hill 47  Types of Mendelian Inheritance Patterns Involving Two Genes Type Description Epistasis An inheritance pattern in which the alleles of one gene mask the phenotypic effects of the alleles of a different gene. Complementation A phenomenon in which two parents that express the same or similar recessive phenotypes produce offspring with a wild-type phenotype. Gene modifier A phenomenon in which an allele of one gene modifies the effect phenotypic outcome of the alleles of a different gene. Gene redundancy A pattern in which the loss of function in a single gene has no phenotypic effect, but the loss of function of two genes has an effect. Functionality of only one of the two genes is necessary for a normal phenotype; the genes are functionally redundant. © McGraw Hill 48  Cross Between Two White Pea Varieties C (one purple-color- and producing) allele is is tasis ntation dominant to c (white) ep eme m pl c o P (another purple-color- producing) allele is dominant to p (white) cc or pp masks P or C alleles, producing white color Access the text alternative for slide images. © McGraw Hill 49  Epistasis Epistasis = a gene can mask the phenotypic effects of another gene Often arise because two (or more) different proteins participate in a common cellular function Example: colorless Enzyme C colorless Enzyme P purple     precusor intermediate pigment Recessive alleles do not produce a functional enzyme © McGraw Hill 50  Gene Modifier Effect Example: Inheritance of coat color in rodents A true-breeding black rat crossed to true-breeding albino results in agouti coat color Agouti have black at the tips of each hair that changes to brown (a mixture of yellow and black) near the root If two F1 agouti animals are crossed, they produce offspring in the following ratios 9 agouti 3 black 4 albino © McGraw Hill 51  Coat Color Inheritance in Rodents Access the text alternative for slide images. © McGraw Hill 52  Gene Redundancy Due to gene redundancy, loss-of-function alleles may have no effect on phenotype Geneticists have developed techniques to directly generate loss-of-function alleles This is called a gene knockout Allows scientists to understand the affects of the gene on structure or function of the organism Many knockouts have no obvious effect on phenotype © McGraw Hill 53  A Molecular Explanation of Gene Redundancy Gene duplication A species may have two or more copies of similar genes Paralogs - not identical If one gene is missing, a paralog may be able to carry out the missing function © McGraw Hill 54  A Molecular Explanation for Gene Redundancy Access the text alternative for slide images. © McGraw Hill 55  Inheritance of Capsule Shape Shepherd’s purse seed capsule shape investigated by George Shull At least one copy of T or V present is triangular Only recessive for both genes ttvv is ovate T and V are redundant Access the text alternative for slide images. © McGraw Hill 56  Ch 4 Mini Study Guide Differentiate wild-type alleles and mutant alleles Describe genetic polymorphism Differentiate how recessive mutants and dominant mutants exert effects (potentially cause disease) Describe incomplete penetrance and recognize examples Define expressivity and norm of reaction Describe how the environment can affect phenotype (ex. temperature, diet) Differentiate incomplete dominance, overdominance, and codominance. Recognize examples of each and predict outcomes of crosses. Describe 3 reasons for a heterozygote advantage Predict outcomes for crosses in cases of X-linked inheritance Define: hemizygous, reciprocal cross, holandric genes, pseudoautosomal inheritance Differentiate sex-influenced and sex-limited inheritance Define the following types of alleles: lethal, semi-lethal, conditional, essential, and non-essential Define pleiotropy and describe types of gene interactions Epistasis Complementation Gene modifier effect Gene redundancy © McGraw Hill 57