Introduction to Genetics PDF

Introduction to genetics CH 4 Dr. Radhika G Bhardwaj Incomplete Dominance, Overdominance, and Codominance  Incomplete Dominance In incomplete dominance the heterozygote exhibits a phenotype that is intermediate between the p...

Introduction to genetics CH 4 Dr. Radhika G Bhardwaj Incomplete Dominance, Overdominance, and Codominance  Incomplete Dominance In incomplete dominance the heterozygote exhibits a phenotype that is intermediate between the phenotypes of the two homozygotes Example: ◦ Flower color in the four o’clock plant ◦ Two alleles C R = wild-type allele for red flower color CW =allele for white flower color Incomplete dominance in the four-o’clock plant CRCWflowers are pink because 50% of the CR protein is not sufficient to produce the red phenotype In the F2 generation, the 1:2:1 phenotypic ratio is not the 3:1 ratio observed in simple Mendelian inheritance  Incomplete Dominance Whether a trait is dominant or incompletely dominant may depend on how closely the trait is examined Take, for example, the characteristic of pea shape ◦ Mendel concluded that ◦ RR and Rr genotypes produced round peas ◦ rr genotypes produced wrinkled peas ◦ However, a microscopic examination of round peas reveals that R and r show incomplete dominance of starch biosynthesis Example of incomplete dominance Wavy hair in humans Curly hair is the dominant trait in humans, whereas straight hair is the recessive trait. In heterozygous species, the resulting phenotype is wavy hair which is an intermediate between straight and curly. Thus, wavy hair results from incomplete dominance where the phenotype results due to the mixing of the two traits. Wavy hair, thus, represents a novel phenotype different from straight or curly hair. Offsprings formed from two parents with homozygous genotypes will have a genotypic ratio of 1:2:1 with the phenotypic ratio or curly: wavy: straight.  Overdominance Overdominance – When a heterozygote has greater reproductive success than the either homozygote ◦ It is also called heterozygote advantage  Overdominance Example: Sickle-cell anemia ◦ 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  Overdominance HbS HbS individuals have red blood cells that deform into a sickle shape under conditions of low oxygen ◦ Two major ramifications 1. Sickling greatly shortens the life span of the red blood cells, resulting in anemia 2. Sickle cells form clumps, blocking capillary circulation ◦ Thus, affected individuals tend to have a shorter life span than unaffected individuals 101 (a, b) Mary Martin/Science Source  Co-dominance Co-dominance is the mechanism of dominance seen in some alleles where both alleles of a gene in a heterozygote lack the dominant and recessive relationship, and each allele is capable of some degree of phenotypic expression.  Multiple Alleles and Codominance Many genes have multiple alleles (that is, three or more) Example: ABO blood type genes in humans ◦ Plasma membranes of red blood cells have oligosaccharides that act as surface antigens ◦ Antigens are recognized by antibodies produced by the immune system 103 Blood Types Three alleles: I A ,I B , and i ◦ i is recessive to both I I A and I B ii has type O blood I AI A and I Ai have type A blood IBIB and I B i have type B blood I AIB has type AB blood Blood Types Alleles I A and I B are codominant ◦ In cells with both alleles the trait is a combination of both phenotypes (codominance) Blood type inheritance Inheritance pattern is different than what would be predicted from two alleles with a strict dominant / recessive relationship Understanding blood type The gene that determines ABO blood type encodes glycosyl transferase which attaches a sugar to the oligosaccharide Three alleles affect this sugar addition ◦ The i allele encodes a defective enzyme that can’t add sugars ◦ The carbohydrate tree is short (called H antigen) I encodes a form of the enzyme that can add the sugar N-acetyl- A galactosamine to the carbohydrate tree (makes A antigen) I encodes a form of the enzyme that can add the sugar B galactose to the carbohydrate tree (makes B antigen) 25 A person with type AB blood has oligosaccharides with both types of sugars 26  Examples of co-dominance Blood type in humans Blood type in humans is determined on the basis of the gene for the proteins that appear on the outside of the blood cells. The alleles present are A, B, and O, where A and B represent two different proteins, but O represents the absence of any proteins. The existence of A and B proteins, like two colors in flowers, can occur together as a result of co-dominance. Thus, if both the proteins A and B are inherited to the offsprings, and both are expressed, AB blood type might occur in the offsprings. However, the blood type O represents a dominant/recessive relationship where if A and B genes are expressed, then O doesn’t get expressed.  Examples of co-dominance Livestock Different animals have different colors on their skin and feathers as a result of co-dominance. When a chicken with white feathers breeds with a chicken with black feathers, the offsprings have both white and black feathers as a result of co- dominance. During co-dominance, both the traits are expressed independently of each other. A similar phenomenon is also observed in cows where the breeding of black and white cows results in cows with the spotting of white and black. As a result of co-dominance, both the traits are expressed independently of each other. Sex-Influenced and Sex- Limited Inheritance Sex-influenced inheritance vs. sex-limited inheritance Predicting the outcome of crosses for sex-influenced inheritance  The inheritance pattern of certain traits is governed by the sex of the individual Sex and Traits There are two main types Sex-influenced Sex-limited traits traits Sex-Influenced Traits An allele is dominant in one sex but recessive in the other ◦ Thus, sex influence is a phenomenon of heterozygotes Sex- influenced does not mean sex-linked ◦ Most sex-influenced traits are autosomal Example: Scurs in cattle ◦ Small growths on the skull ◦ Dominant in males, recessive in females Sc P and Sc A (scurs present and absent) ScP is dominant in males; Sc A is dominant in females 32 Courtesy of Sheila M. Schmutz, Ph.D. 34 Cattle scur alleles Genotype Phenotype Males Females ScPScP Scurs Scurs ScPSc A Scurs No scurs (hornless) Sc ASc A No scurs No scurs 35 Sex-Limited Traits Traits that occur in only one of the two sexes ◦ Responsible for sexual dimorphism ◦ May be autosomal or sex-linked Example: Human sexual dimorphism ◦ Ovaries in females, testes in males Example: Bird plumage and features ◦ Roosters have more ornate plumage than hens, and larger comb and wattles 36 (a) Pixtal/agefotostock; (b) ©Image Source/PunchStock  Lethal Alleles Different types of lethal alleles Predicting how lethal alleles may affect the outcome of a cross Essential genes – Genes that are required for survival Absence of the protein product leads to a lethal phenotype It is estimated that about 1/3 of all genes are essential So, mutations in these genes can form lethal alleles Nonessential genes – Those not required for survival But nonessential genes still benefit the organism  Lethal Alleles A lethal allele is one that has the potential to cause the death of an organism ◦ These alleles are typically the result of mutations in essential genes ◦ They are usually inherited in a recessive manner 40 Many lethal alleles prevent cell division ◦ Kill an organism at an early stage Some lethal alleles exert their effect later in life ◦ Example: Huntington disease ◦ Progressive degeneration of the nervous system, dementia and early death ◦ The age of onset for the disease is usually between 30 to 50 41  Conditional Lethal and Semilethal Alleles Conditional lethal alleles kill an organism only under certain environmental conditions ◦ Temperature-sensitive (ts) lethals ◦ A developing Drosophila larva may be killed at 30° C but will survive if grown at 22° C ◦ Typically, temperature-sensitive proteins misfold at higher temperatures, becoming nonfunctional Semilethal alleles ◦ Kill some individuals in a population, not all of them ◦ Environmental factors and other genes may help prevent the detrimental effects of semilethal genes 42  How Lethal Alleles Affect Mendelian Ratios A lethal allele may produce ratios that seemingly deviate from Mendelian ratios ◦ Example: the Manx cat ◦ A dominant mutation that affects the spine ◦ This mutation shortens the tail in heterozygotes ◦ But is lethal as a homozygote – so MM are never seen and are missing from offspring ratios 43 Juniors Bildarchiv GmbH/Alamy Stock Photo  Complex phenotypes caused by mutations in single genes Explain the phenomenon of pleiotropy How embryonic development determines certain coat patterns  Pleiotropic Effects Multiple effects of a single gene on the phenotype of an organism is called pleiotropy ◦ Most genes can be pleiotropic Occurs because ◦ The gene product may affect cell function in multiple ways ◦ Example: Microtubule proteins affect cell division and movement ◦ The gene may be expressed in different cell types ◦ Example: Expression in muscle cells and nerve cells ◦ The gene may be expressed at different stages of development ◦ Example: Expression in embryo and later in adult Pleiotropic Effects2 Example: Cystic fibrosis ◦ Normal 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 ◦ Mucus can block tubes that carry digestive enzymes ◦ On the skin, causes salty sweat ◦ Thus, defect in CFTR can have multiple effects 48  Coat Color Patterns Determined by Events in Embryonic Development Many dogs and mammals have white spotting on their coats, where portions of the fur lack pigmentation Multiple alleles S + allele = full pigmentation (no white spotting) SI allele = Irish spotting S W allele = extreme white spotting Spotting gene encodes microphthalmia-associated transcription factor (MITF)- required for proper migration, proliferation, and survival of melanoblasts Reduced expression of MITF causes regions farthest from spinal cord to contain fewer melanocytes; causes white spotting 49 (a, b) ©Deanna Vout Gene Interactions Gene interactions occur when two or more different genes influence the outcome of a single trait Indeed, morphological traits such as height, weight and pigmentation are affected by many different genes in combination with environmental factors 52 TABLE 5.3 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 different parents that express the same or similar recessive phenotypes produce offspring with a wild-type phenotype. Gene modification A phenomenon in which an allele of one gene modifies the phenotypic outcome of the alleles of a different gene. Gene redundancy A phenomenon 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. A Cross Involving a Two-Gene Interaction Can Produce Two Distinct Phenotypes Due to Epistasis Example: Flower color in the sweet pea ◦ Lathyrus odoratus normally has purple flowers ◦ Bateson and Punnett obtained several true-breeding varieties with white flowers ◦ Crossing them together resulted in purple flowers ◦ The two genes complemented each other ◦ This is a way of saying the mutations were in different genes ◦ Thus each strain contributed a wild-type allele Epistasis 1 They allowed the purple hybrids to self-fertilize ◦ This produced interesting results ◦ C is dominant to c ◦ P is dominant to p ◦ But cc masks the P allele ◦ And pp masks the C allele ◦ We say that cc is epistatic to Pp (or PP) ◦ And pp is epistatic to Cc (or CC) ◦ Both enzymes are needed to produce purple pigment 133 Epistasis 2 Epistasis – when a gene can mask the phenotypic effects of another gene Epistatic interactions often arise because two different proteins participate in a common cellular function ◦ For example, an enzymatic pathway If an individual is homozygous for either recessive allele ◦ It will not make a functional enzyme required for the production of purple pigment: (cc) no enzyme C, (pp) no enzyme P ◦ Therefore, the flowers remain white 58 What is the difference between epistasis and dominance? Epistasis is a relationship between alleles of two different genes. Whereas dominance refers to the relationship between two variants or alleles of the same gene. TABLE 5.1 Types of Mendelian Inheritance Patterns Involving Single Genes Type Description Simple Inheritance: As described in Chapter 3, this term is commonly applied to the inheritance of Mendelian alleles that obey Mendel’s laws and follow a strict dominant/recessive relationship. In this chapter, we will see that some genes occur as three or more alleles, making the dominant/recessive relationship more complex. Molecular: The dominant allele encodes a functional protein, and 50% of the protein is sufficient to produce the dominant trait. X-linked Inheritance: As described in Chapter 4, this pattern involves the inheritance of genes that are located on the X chromosome. In mammals and fruit flies, males have a single copy of X - linked genes, whereas females have two copies. Molecular: If a pair of X-linked alleles shows a simple dominant/recessive relationship, the dominant allele encodes a functional protein, and 50% of the protein is sufficient to produce the dominant trait in a heterozygous female. Males have only one copy of X-linked genes and therefore express the copy they carry. Incomplete Inheritance: This pattern occurs when a dominant phenotype is not expressed even though an penetrance individual carries a dominant allele. An example is an individual who carries the polydactyly allele but has a normal number of fingers and toes. Molecular: Even though a dominant gene may be present, the protein encoded by the gene may not exert its effects. This can be due to environmental influences or to other genes that may encode proteins that counteract the effects of that from the dominant allele. Incomplete Inheritance: This pattern occurs when the heterozygote has a phenotype that is intermediate dominance between either corresponding homozygote. For example, a cross between homozygous red- flowered and homozygous white-flowered parents produces heterozygous offspring with pink flowers. Molecular: 50% of a functional protein is not sufficient to produce the same trait as in a homozygote with 100% of that protein. 74 TABLE 5.1 Types of Mendelian Inheritance Patterns Involving Single Genes Type Description Overdominance Inheritance: This pattern occurs when the heterozygote has a trait that confers a greater level of reproductive success than either homozygote has. Molecular: Three common ways that heterozygotes may gain benefits: (1) Their cells may have increased resistance to infection by microorganisms; (2) they may produce more forms of protein dimers with enhanced function; or (3) they may produce proteins that function under a wider range of conditions. Codominance Inheritance: This pattern occurs when the heterozygote expresses both alleles simultaneously without forming an intermediate phenotype. For example, with regard to human blood types, an individual carrying the A and B alleles has an AB blood type. Molecular: The codominant alleles encode proteins that function slightly differently from each other, and the function of each protein in the heterozygote affects the phenotype uniquely. Sex-influenced Inheritance: This pattern refers to the effect of sex on the phenotype of the individual. Some inheritance alleles are recessive in one sex and dominant in the opposite sex. Molecular: Sex hormones may regulate the molecular expression of genes. This regulation can influence the phenotypic effects of alleles. Sex-limited Inheritance: In this pattern, a trait occurs in only one of the two sexes. An example is breast inheritance development in mammals. Molecular: Sex hormones may regulate the molecular expression of genes. This regulation can influence the phenotypic effects of alleles. In this pattern of inheritance, sex hormones that are primarily produced in only one sex are essential for an individual to display a particular phenotype. Lethal alleles Inheritance: A lethal allele is one that has the potential of causing the death of an organism. Molecular: Lethal alleles are most commonly loss-of-function alleles that encode proteins that are necessary for survival. In some cases, such an allele may be due to a mutation in a nonessential gene that changes a protein so that it functions with abnormal and detrimental consequences.