Extensions of Mendelian Genetics PowerPoint® Lecture Presentation for Concepts of Genetics Ninth Edition Klug, Cummings, Spencer, Palladino Chapter 4 Extensions of Mendelian Genetics Lectures by David Kass with contributions from John C. Osterman. Copyright © 2009 Pearson Education, Inc.

Alleles Alternative forms of a gene are called alleles. Mutation is the source of alleles. The wild-type allele is the one that occurs most frequently in nature and is usually, but not always, dominant.

Mutations Loss-of-function mutations Null alleles Gain-of-function mutations Neutral mutations

Phenotypic traits may be influenced by more than one gene and the allelic forms of each gene involved.

Allelic Symbols Used Dominant alleles are usually indicated either by: an italic uppercase letter (D) Recessive alleles are usually indicated either by: an italic lowercase letter (d)

Allelic Symbols Used System Used for Drosophila melanogaster e+/e+ gray homozygote (wild type) e+/e gray heterozygote (wild type) e/e ebony homozygote (mutant) +/+ gray homozygote (wild type) +/e gray heterozygote (wild type) Wr/Wr wrinkled-wing homozygote (mutant) Wr/Wr+ wrinkled-wing heterozygotes (mutant) Wr+/Wr+ normal wings (wild type)

Allelic Symbols Used If no dominance exists, italic uppercase letters and superscripts are used to denote alternative alleles (R1, R2, CW, CR).

Incomplete Dominance In incomplete dominance: neither trait is dominant offspring from a cross between parents with contrasting traits may have an intermediate phenotype

The phenotypic ratio is identical to the genotypic ratio in cases of incomplete dominance. Figure 4.1

Incomplete Dominance The threshold effect comes about if normal phenotypic expression occurs whenever a certain level (usually 50% or less) of gene product is attained. Ex. Tay-Sachs Disease

Codominance Codominance One example is the MN blood group. both alleles are expressed in the heterozygote One example is the MN blood group.

Multiple Allelism Multiple alleles (>2) can be studied only in populations, because any individual will have at most two alleles of the same gene.

Multiple Allelism – ABO Blood Group Alleles present in population: A, B, O alleles Each individual has the A, B, AB, or O phenotype IA and IB alleles are dominant to the IO allele IA and IB alleles are codominant

Figure 4.2

Bombay Phenotype Figure 4-3 A partial pedigree of a woman displaying the Bombay phenotype. Functionally, her ABO blood group behaves as type O. Genetically, she is type B. Figure 4.3

Recessive Lethal Alleles Loss-of-function mutation can sometimes be tolerated in the heterozygous state but may behave as a recessive lethal allele in the homozygous state. In this case, homozygous recessive individuals will not survive.

Figure 4.4

Dominant Lethal Alleles In some cases, a mutation can be a dominant lethal allele, in which case the heterozygote will not survive. Ex. Huntington disease For dominant lethal alleles to exist, the affected individual must reproduce before dying.

Mendel – Independent Assortment Mendel’s principle of independent assortment applies to situations in which two modes of inheritance occur simultaneously, provided that the genes controlling each character are not linked on the same chromosome.

Figure 4.5

Phenotypes Affected by Many Genes In gene interaction, the cellular function of numerous gene products contributes to the development of a common phenotype. Epigenesis – often a phenotype occurs due to many steps in a developmental process that are influenced and controlled by many genes. Ex. Development of organs

Epistasis Epistasis occurs when: one gene masks the effect of another gene, or two gene pairs complement each other such that one dominant allele is required at each locus to express a certain phenotype Ex. Bombay effect

Figure 4.6

Figure 4-7 Generation of the various modified dihybrid ratios from the nine unique genotypes produced in a cross between individuals heterozygous at two genes. Figure 4.7

Section 4.8 Eight cases of epistasis are described in Figure 4.8. These include recessive epistasis (case 1), dominant epistasis (case 2), and complementary gene interaction (case 3).

Figure 4.8

Figure 4-9 Summer squash exhibiting various fruit-shape phenotypes, where disc (white), long (orange gooseneck), and sphere (bottom left) are apparent. Figure 4.9

Eye color in Drosophila Eye color in Drosophila. Interaction of two gene products result in the wild-type eye color, which is brick red. Figure 4-10 A theoretical explanation of the biochemical basis of the four eye-color phenotypes produced in a cross between Drosophila with brown eyes and scarlet eyes. In the presence of at least one wild-type bw+ allele, an enzyme is produced that converts substance b to c, and the pigment drosopterin is synthesized. In the presence of at least one wild-type st+ allele, substance e is converted to f, and the pigment xanthommatin is synthesized. The homozygous presence of the recessive bw and st mutant alleles blocks the synthesis of these respective pigment molecules. Either one, both, or neither of these pathways can be blocked, depending on the genotype. Figure 4.10

Complementation Analysis Two cases of mutation in Drosophila (Figure 4.11) Case 1: All offspring develop normal wings Case 2: All offspring fail to develop normal wings

Figure 4.11

Pleiotropy Pleiotropy occurs when expression of a single gene has multiple phenotypic effects, and it is quite common. Examples of pleiotropy are Marfan syndrome and porphyria variegata. Abraham_Lincoln_standing_portrait_1863.jpg Flo Hyman

X-Linkage Genes present on X chromosome exhibit unique patterns of inheritance due to presence of only one X chromosome in males.

X-Linkage Drosophila eye color one of the first examples of X-linkage described

Hemizygosity Hemizygosity Occurs in males due to the inability of males to be homozygous or heterozygous for an X-linked gene Have only one copy of that gene despite having diploid cells

Figure 4-14 (a) A human pedigree of the X-linked color-blindness trait Figure 4-14 (a) A human pedigree of the X-linked color-blindness trait. (b) The most probable genotypes of each individual in the pedigree. The photograph is of an Ishihara color-blindness chart. Red-green color-blind individuals see a 3 rather than the 8 visualized by those with normal color vision. Figure 4.14

Figure 12-31 part 2 Hemophilia among the royal families of Europe A famous genetic pedigree involves the transmission of sex-linked hemophilia from Queen Victoria of England (seated center front, with cane, 1885) to her offspring and eventually to virtually every royal house in Europe. Because Victoria's ancestors were free of hemophilia, the hemophilia allele must have arisen as a mutation either in Victoria herself or in one of her parents (or as a result of marital infidelity). Extensive intermarriage among royalty spread Victoria's hemophilia allele throughout Europe. Her most famous hemophiliac descendant was great-grandson Alexis, Tsarevitch (crown prince) of Russia. The Tsarina Alexandra (Victoria's granddaughter) believed that only the monk Rasputin could control Alexis's bleeding. Rasputin may actually have used hypnosis to cause Alexis to cut off circulation to bleeding areas by muscular contraction. The influence that Rasputin had over the imperial family may have contributed to the downfall of the tsar during the Russian Revolution. In any event, hemophilia was not the cause of Alexis's death; he was killed with the rest of his family by the Bolsheviks (Communists) in 1918.

Lethal X-Linked Recessive Disorders Lethal X-linked recessive disorders are observed only in males. Usually never reproduce Females can only be heterozygous carriers that do not develop the disorders.

Individual’s Sex Can Influence Phenotype Sex-limited inheritance occurs in cases where the expression of a specific phenotype is absolutely limited to one sex. In sex-influenced inheritance, the sex of an individual influences the expression of a phenotype that is not limited to one sex or the other.

Figure 4-15 Hen feathering (left) and cock feathering (right) in domestic fowl. The hen’s feathers are shorter and less curved. Figure 4.15

Figure 4-16 Pattern baldness, a sex-influenced autosomal trait in humans.

Epigenetics Phenotypic expression of a trait may be influenced by environment as well as by genotype.

Figure 4-19 (a) A Himalayan rabbit. (b) A Siamese cat Figure 4-19 (a) A Himalayan rabbit. (b) A Siamese cat. Both show dark fur color on the muzzle, ears, and paws. These patches are due to the effect of a temperature-sensitive allele responsible for pigment production at the lower temperatures of the extremities, which is inactive at slightly higher temperatures. Figure 4.19

Genomic (Parental) Imprinting In cases of genomic (parental) imprinting, phenotypic expression may depend on the parental origin of the chromosome. Imprinting is thought to occur before or during gamete formation and may involve DNA methylation.

The End