Creative Education 2012. Vol.3, Special Issue, 884-889 Published Online October 2012 in SciRes (http://www.SciRP.org/journal/ce) http://dx.doi.org/10.4236/ce.2012.326133 Analogies for Teaching Mutant Allele Dominance Concepts Rebecca L. Seipelt-Thiemann Biology Department, Middle Tennessee State University, Murfreesboro, USA Email: [email protected] Received August 29th, 2012; revised September 27th, 2012; accepted October 9th, 2012 Analogies connect new and familiar concepts and ideas by providing a comfortable and known frame- work within which students can integrate new concepts. Use of analogies to aid understanding of abstract and/or complex ideas is commonly used in molecular sciences, such as genetics, molecular biology, and biochemistry. Five analogies for different mechanisms of mutant allele dominance, a seemingly counter- intuitive idea in genetics, were designed and assessed in an upper division undergraduate/masters level course. Each of the five mechanisms, haploinsufficiency, acquired function, poison product, increased ac- tivity, and inappropriate expression, was described in the context of a human disease and molecular mechanism and followed by a descriptive analogy which mirrored the molecular mechanism using real world items or a video clip. The majority of students reported increased interest, understanding, and en- gagement following the analogies, as well as decreased confusion. Keywords: Analogy; Genetics; Allele Dominance Introduction a non-intuitive concept, mutant allele dominance. Dominance and recessiveness are terms used to describe both The constructivist model of learning suggests that students phenotypes and alleles/genes. However, students generally learn by connecting new ideas into an existing framework of simply accept the use of the terms without understanding why a knowledge. Analogies are commonly used by students, teachers, mutant allele is considered dominant or recessive or how the and text books to make these connections, particularly where alleles actually generate the mutant or normal phenotype. Re- abstract concepts or ideas are involved. Regardless of type, cessiveness of a mutant allele is more easily understood by analogies share common features, such as the familiar concept students for a number of reasons. First, there is one model ex- or idea (analog), the new concept or idea (target), elements of planation for recessiveness; that is, the single wildtype allele in similarity between the analog and target (links, features, or a heterozygote produces sufficient gene product to obtain a attributes), and the mapping of similarities between the target “normal” phenotype. Second, this explanation can be extended and analog (Glynn, 1995). Even though all analogies share by the knowledge that most gene products are enzymes, which those common features, they vary significantly in their makeup, are not destroyed in a chemical reaction, but continuously con- for example, whether the analog is scientific or non-scientific, vert substrate to the needed cellular product. However, the whether the analogy is planned or not, whether the analogy is dominance of a mutant allele in a heterozygote is counter-in- student or teacher-initiated, and whether the analog and target tuitive since the presence of a single wildtype, functional allele are concrete or abstract (Oliva, Axcarate, & Navarrete, 2007). It is not sufficient to generate a normal phenotype. Additionally, is also important to note that six general elements are consid- the interaction of the dominant mutant and the wildtype reces- ered important for analogy use, but not do not necessarily al- sive allele at the molecular level can be very specific to the ways follow the same systematic order: 1) target introduction, 2) function of the encoded mutant or wildtype protein. To this end, analog review, 3) feature identifications, 4) analog-target simi- five general examples explain a large number of valid mecha- larity mapping, 5) analogy breakdown, and 6) analogy conclu- nisms of mutant allele dominance: haploinsufficiency, acquired sion (Oliva, Axcarate, & Navarrete, 2007; Glynn, 2007; Glynn, function, poison product, increased enzyme activity, and inap- 2008). propriate expression. As these mechanisms are counter-intuitive, Analogies are used in all levels and subdisciplines in biology, an active analogy for each mechanism in connection with a but none so much as in the more abstract areas of genetics, specific human genetic disease was developed and used in the molecular biology, and biochemistry. Indeed, the fact that the classroom to aid students in understanding these specific mo- term “gene” has many different definitions, depending on his- lecular mechanisms and thus the mechanisms of mutant allele torical and scientific context (Gericke & Hagberg, 2007; Smith dominance. Student assessments of the analogies suggest the & Adkison, 2010), further complicates both introductory and majority of students are more engaged, have increased under- advanced instruction in these disciplines. Tibell and Rundgren standing, and have decreased confusion. (2010) suggest domain-specific visualization tools will aid in student learning of complex and abstract concepts. Here, five Study Purpose visual and hands-on analogies for use in genetics are described with the aim of helping students gain a greater understanding of The purpose of this study was to generate and assess teaching 884 Copyright © 2012 SciRes. R. L. SEIPELT-THIEMANN tools that may enable students to gain an increased understand- ing of molecular mechanisms of mutant allele dominance. Procedures and Relevant Descriptions First, a verbal and visual description of the dominance mechanism was introduced using one powerpoint slide per mechanism that included a list of symptoms included in the phenotype for a specific human genetic disease, a picture of an affected person, and either a drawing or micrograph of the mo- lecular appearance of the trait. Next, each active analogy dis- cussed in the context of the disease mechanism and then dem- onstrated to or engaged in by the students. The analogy was Figure 1. linked back to the specific human disease verbally. Students Examples of Analogy Visuals. (A)-(B) Haploinsufficiency (homozy- then filled out a short survey asking them to rate their: 1) un- gous wildtype vs. heterozygous); (C)-(D) Poison product (heterozygous derstanding, 2) engagement, 3) interest, and 4) confusion for before vs. after cellular destruction of “poisoned complexes”; (E)-(F) each model before the analogy on a scale of 1 - 5. The survey Acquired function (normal function vs. acquired function). asked them to gauge whether these items went “up”, “down”, or remained the “same” for each model/mechanism. Finally, stu- to perform some alternate function in a different biological dents were asked to rank the analogies on which helped under- pathway or process. In this case, the phenotype may have noth- standing the most and why. ing to do with the normal function of the protein, but instead result from destroying or altering a second, unrelated pathway Mechanism 1: Haploinsufficiency or process. The human molecular example of acquired function was The explanation for mutant allele dominance by haploinsuf- sickle cell anemia variant Antilles. Sickle cell anemia can be ficiency is probably the easiest to understand relative to the caused by several different mutations in the beta globin gene recessiveness model since it uses similar reasoning. The idea is (HBB, OMIM #141900, 2012). One mutation in the beta globin that either the wildtype allele produces a minimally active pro- gene, which is dominant, is the HbS Antilles allele (OMIM tein or the amount of protein required is so great that the normal #141900.0244, 2012). Wildtype hemoglobin, which is com- phenotype is only generated when both alleles produce func- posed of both beta and alpha globin, functions to carry oxygen tional product. in red blood cells. This mutation, a change of valine to isoleu- The human molecular example of haploinsufficiency was cine at amino acid 23 (V23I), results in a modified hemoglobin Stickler syndrome I (Online Mendelian Inheritance in Man molecule that polymerizes into long rods (Herrick, 1910). (OMIM) #108300, 2012). Stickler syndrome I is a dominantly These rods deform the normally pliable red blood cell into a inherited disease caused by mutations in the COL2A1 gene rigid sickle-shaped cell. Abnormal red blood cells then occlude which normally produces a structural protein found in cartilage tiny capillaries and deprive tissue of necessary oxygen resulting and the vitreous humor of the eye (Korkko, Ritvaniemi, Haataja, in sickle cell crisis. Kaariainen, Kivirikko, Prockop, & Ala-Kokko, 1993). Het- The analogy involved creating a structural tangle (Sickle cell rods) using an object with a different known function (a clothes erozygotes exhibit myopia progressing to retinal detachment, hanger). Students were shown a hanger and asked the function among other traits, due to structural defects resulting from in- (to hang up clothes, Figure 1(C)). Equal numbers of plastic sufficient COL2A1 production during development (Richards, hangers (wildtype proteins) and wire hangers (HbS proteins) Baguley, Yates, Lane, Nicol, Harper, Scott, & Snead, 2000). were placed in a sack and shaken to simulate low oxygen ten- The analogy involved building a structure (collagen) using sion. This generated a tangle of hangers (Figure 1(D)), mim- plastic blocks to represent COL2A1 proteins. Students