Analogies for Teaching Mutant Allele Dominance Concepts

doi:10.4236/ce.2012.326133

Paper Menu >>

Journal Menu >>

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

884

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

The constructivist model of learning suggests that students

learn by connecting new ideas into an existing framework of

knowledge. Analogies are commonly used by students, teachers,

and text books to make these connections, particularly where

abstract concepts or ideas are involved. Regardless of type,

analogies share common features, such as the familiar concept

or idea (analog), the new concept or idea (target), elements of

similarity between the analog and target (links, features, or

attributes), and the mapping of similarities between the target

and analog (Glynn, 1995). Even though all analogies share

those common features, they vary significantly in their makeup,

for example, whether the analog is scientific or non-scientific,

whether the analogy is planned or not, whether the analogy is

student or teacher-initiated, and whether the analog and target

are concrete or abstract (Oliva, Axcarate, & Navarrete, 2007). It

is also important to note that six general elements are consid-

ered important for analogy use, but not do not necessarily al-

ways follow the same systematic order: 1) target introduction, 2)

analog review, 3) feature identifications, 4) analog-target simi-

larity mapping, 5) analogy breakdown, and 6) analogy conclu-

sion (Oliva, Axcarate, & Navarrete, 2007; Glynn, 2007; Glynn,

2008).

Analogies are used in all levels and subdisciplines in biology,

but none so much as in the more abstract areas of genetics,

molecular biology, and biochemistry. Indeed, the fact that the

term “gene” has many different definitions, depending on his-

torical and scientific context (Gericke & Hagberg, 2007; Smith

& Adkison, 2010), further complicates both introductory and

advanced instruction in these disciplines. Tibell and Rundgren

(2010) suggest domain-specific visualization tools will aid in

student learning of complex and abstract concepts. Here, five

visual and hands-on analogies for use in genetics are described

with the aim of helping students gain a greater understanding of

a non-intuitive concept, mutant allele dominance.

Dominance and recessiveness are terms used to describe both

phenotypes and alleles/genes. However, students generally

simply accept the use of the terms without understanding why a

mutant allele is considered dominant or recessive or how the

alleles actually generate the mutant or normal phenotype. Re-

cessiveness of a mutant allele is more easily understood by

students for a number of reasons. First, there is one model ex-

planation for recessiveness; that is, the single wildtype allele in

a heterozygote produces sufficient gene product to obtain a

“normal” phenotype. Second, this explanation can be extended

by the knowledge that most gene products are enzymes, which

are not destroyed in a chemical reaction, but continuously con-

vert substrate to the needed cellular product. However, the

dominance of a mutant allele in a heterozygote is counter-in-

tuitive since the presence of a single wildtype, functional allele

is not sufficient to generate a normal phenotype. Additionally,

the interaction of the dominant mutant and the wildtype reces-

sive allele at the molecular level can be very specific to the

function of the encoded mutant or wildtype protein. To this end,

five general examples explain a large number of valid mecha-

nisms of mutant allele dominance: haploinsufficiency, acquired

function, poison product, increased enzyme activity, and inap-

propriate expression. As these mechanisms are counter-intuitive,

an active analogy for each mechanism in connection with a

specific human genetic disease was developed and used in the

classroom to aid students in understanding these specific mo-

lecular mechanisms and thus the mechanisms of mutant allele

dominance. Student assessments of the analogies suggest the

majority of students are more engaged, have increased under-

standing, and have decreased confusion.

Study Purpose

The purpose of this study was to generate and assess teaching

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

linked back to the specific human disease verbally. Students

then filled out a short survey asking them to rate their: 1) un-

derstanding, 2) engagement, 3) interest, and 4) confusion for

each model before the analogy on a scale of 1 - 5. The survey

asked them to gauge whether these items went “up”, “down”, or

remained the “same” for each model/mechanism. Finally, stu-

dents were asked to rank the analogies on which helped under-

standing the most and why.

Mechanism 1: Haploinsufficiency

The explanation for mutant allele dominance by haploinsuf-

ficiency is probably the easiest to understand relative to the

recessiveness model since it uses similar reasoning. The idea is

that either the wildtype allele produces a minimally active pro-

tein or the amount of protein required is so great that the normal

phenotype is only generated when both alleles produce func-

tional product.

The human molecular example of haploinsufficiency was

Stickler syndrome I (Online Mendelian Inheritance in Man

(OMIM) #108300, 2012). Stickler syndrome I is a dominantly

inherited disease caused by mutations in the COL2A1 gene

which normally produces a structural protein found in cartilage

and the vitreous humor of the eye (Korkko, Ritvaniemi, Haataja,

Kaariainen, Kivirikko, Prockop, & Ala-Kokko, 1993). Het-

erozygotes exhibit myopia progressing to retinal detachment,

among other traits, due to structural defects resulting from in-

sufficient COL2A1 production during development (Richards,

Baguley, Yates, Lane, Nicol, Harper, Scott, & Snead, 2000).

The analogy involved building a structure (collagen) using

plastic blocks to represent COL2A1 proteins. Students were

given eight lego blocks (COL2A1 proteins) and asked to stack

them in sets of two. They were told that four stacks of two were

sufficient for the wild-type phenotype (homozygous wild-type,

Figure 1(A)). Students were then asked to break down the

blocks, remove four of them, mimicking a deletion at one allele

(heterozygous, Figure 1(B)). Students were asked to re-stack

the blocks in sets of two. Again, four sets were required for a

normal phenotype, but were not produced illustrating that at

times 50% production is insufficient for a maintenance of reti-

nal attachment (wildtype phenotype).

Mechanism 2: Acquired Function

The acquired function explanation for mutant allele domi-

nance involves the mutant allele encoding a protein that has

acquired something “extra” and is therefore responsible for the

abnormal phenotype. The mutant allele may encode a regulated

protein whose control has been lost or the protein may be able

Figure 1.

Examples of Analogy Visuals. (A)-(B) Haploinsufficiency (homozy-

gous wildtype vs. heterozygous); (C)-(D) Poison product (heterozygous

before vs. after cellular destruction of “poisoned complexes”; (E)-(F)

Acquired function (normal function vs. acquired function).

to perform some alternate function in a different biological

pathway or process. In this case, the phenotype may have noth-

ing to do with the normal function of the protein, but instead

result from destroying or altering a second, unrelated pathway

or process.

The human molecular example of acquired function was

sickle cell anemia variant Antilles. Sickle cell anemia can be

caused by several different mutations in the beta globin gene

(HBB, OMIM #141900, 2012). One mutation in the beta globin

gene, which is dominant, is the HbS Antilles allele (OMIM

#141900.0244, 2012). Wildtype hemoglobin, which is com-

posed of both beta and alpha globin, functions to carry oxygen

in red blood cells. This mutation, a change of valine to isoleu-

cine at amino acid 23 (V23I), results in a modified hemoglobin

molecule that polymerizes into long rods (Herrick, 1910).

These rods deform the normally pliable red blood cell into a

rigid sickle-shaped cell. Abnormal red blood cells then occlude

tiny capillaries and deprive tissue of necessary oxygen resulting

in sickle cell crisis.

The analogy involved creating a structural tangle (Sickle cell

rods) using an object with a different known function (a clothes

hanger). Students were shown a hanger and asked the function

(to hang up clothes, Figure 1(C)). Equal numbers of plastic

hangers (wildtype proteins) and wire hangers (HbS proteins)

were placed in a sack and shaken to simulate low oxygen ten-

sion. This generated a tangle of hangers (Figure 1(D)), mim-

icking the polymerization of the hemoglobin rods that generate

the inflexible, sickle-shaped red blood cell.

Mechanism 3: Poison Product

The explanation for mutant allele dominance by poison

product is probably least intuitive because it involves protein

quaternary structure and probability. Generally, one mutant

protein in a protein complex initiates the cell’s quality control

mechanism and destroys the entire protein complex. This re-

sults in only 25% normal protein complexes being present, thus

leading to a more severe phenotype than simple allele loss.

The human molecular example of poison product was osteo-

genesis imperfecta, type II (OMIM #166210, 2011). Patients

with this inherited disease have very brittle bones and severely

weakened heart valves that must be monitored closely if the

patient survives. This disease is caused by a mutation in the

alpha 1 collagen gene, which produces a protein that is a pri-

mary building block for structural collagen in bones. The col-

R. L. SEIPELT-THIEMANN

lagen trimer is composed of two molecules of alpha 1 and one

molecule of alpha 2. In heterozygotes, each trimer can contain

no, one, or two mutant alpha 1 molecules; however, only purely

wildtype trimers are not degraded by the cell. Therefore, only

25% of the original trimers are available to build structural

integrity, resulting in the brittle bones and weak heart valves

observed in the disease (Williams & Prockop, 1983).

The analogy involved building structures (collagen trimers)

using wooden blocks (alpha 1 collagen) and other miscellane-

ous materials (alpha 2 collagen, Figure 1(E)). Students were

given eight small wooden blocks among other items such as

crayons and rubberbands. Half of the blocks were marked with

an “X” to denote one allele’s “worth” of mutant alpha 1 colla-

gen molecules. Students were asked to build four identical

structures without looking at the “X” status of the blocks. Stu-

dents were then asked to destroy all structures containing a

mutant alpha 1 molecule (Figure 1(F)). On average one mole-

cule of the four remained in each group, illustrating how pro-

duction of 50% mutant alpha 1 collagen molecules could result

in only 25% normal collagen trimers which results in the ex-

tremely weakened bones and heart valves observed in osteo-

genesis imperfecta patients.

Mechanism 4: Increased Enzyme Activity

The increased enzyme activity explanation for mutant allele

dominance was that the enzyme encoded by the mutant allele is

more active than the wildtype enzyme and generates too much

product in a biochemical reaction or pathway. Build up of the

product or shunting the product to a different pathway gener-

ates the phenotype.

The human molecular example of increased enzyme activity

was hereditary gout. Hereditary gout can be caused by a muta-

tion in the PRPS (phosphoribosylpyrophosphate synthetase

gene (OMIM #300661, 2012). The metabolic/biochemical

pathway functions as a certain rate and when PRPS activity

increases, the pathway becomes overloaded so that product is

shunted to another pathway whose final product is uric acid

(Becker, Meyer, & Seegmiller, 1973). Uric acid crystallizes in

the fluid-filled spaces of the joints producing the severe joint

pain characterizing gout.

The analogy for increased enzyme activity was illustrated

using a film clip freely available on the internet. Students were

shown a video clip from the “I Love Lucy” show in which Lucy

works in a candy factory (Oppenheimer, Pugh, Carroll, & Asher,

1952). A reliably available clip of this scene can be found at

http://www.youtube.com/watch?v=0YGF5R9i53A (Busciglio,

2010). At normal speed, the candy (the product), is acted upon

by people (enzymes) to produce a box of wrapped candy (the

final product). However, when the pathway speed is increased,

via an upstream overactive enzyme, Lucy is unable to wrap

candy pieces and place them back on the conveyor belt. She

starts pulling candy off the conveyor belt without wrapping it

(buildup of intermediate product), and finally, puts candy in her

hat and shirt (shunting the product to an alternate path). This

film clip humorously illustrates how alleles for overactive en-

zymes, such as PRPS in hereditary gout, can produce unneces-

sary products that generate a phenotype even though a normal

allele is also present with the mutant allele.

Mechanism 5: Inappropriate Expression

The explanation for mutant allele dominance via inappropri-

ate expression involves altered control of gene expression ra-

ther than production of a mutant protein. A functional protein is

expressed, but in the wrong tissue or at the wrong time during

development. The presence of the protein and its functionality

produces the mutant phenotype.

The human molecular example of inappropriate expression

was chronic myeloid leukemia. Chronic myeloid leukemia is

caused by a fusion of chromosomes 9 and 22 that puts the ABL

oncogene under the control of a BCR locus (OMIM #608232,

2012). This inappropriate expression of a growth-promoting

protein drives proliferation of immune cells generating cancer

(De Klein, Van Kessel, Grosveld, Bartram, Hagemeijer, Bootsma,

Spurr, Heisterkamp, Groffen, & Stephenson, 1982).

The analogy for inappropriate expression involved the use of

texting-type language in a more formal situation (Table 1).

Students were directed to an internet site listing the “texting”

version of many common phrases, such as TTYL denotes “talk

to you later” and “2moro” for tomorrow. See NetLingo for

numerous examples at http://www.netlingo.com/acronyms.php.

It was agreed that this type of shorthand is generally acceptable

while texting, but then students were asked whether it was ap-

propriate to use these for 50% of the language (one mutant

“texting” allele and one wildtype allele) in a formal paper, such

as those assigned in English classes, or on essay questions in

exams. This example illustrates how appropriate timing, whether

it is expression of proliferation-promoting genes or use of for-

mal language, is critical for a good outcome (normal phenotype

or a decent grade).

Extending the Experience

 Present a genetic disease with a known molecular cause and

ask students to make a hypothesis as to whether the mutant

allele is dominant or recessive and if dominant, then iden-

tify to which mechanism it is most similar.

 Have students categorize known dominant genetic diseases

based by mechanism based on molecular information.

 Have students develop their own analogy for each mecha-

nism using different genetic diseases.

Results

The main objective of this study was to present analogies

involving the complex and counter-intuitive mechanisms of

mutant allele dominance to the molecular biology education

Table 1.

Selected texting acronyms and their meaningsa.

Text speak /Acronym Meaning

addy address

b4 before

nesec any second

ntim not that it matters

ooo out of office

ptp pardon the pun

slm see last mail

Note: aPlease see NetLingo at http://www.netlingo.com/acronyms.php/.

886

R. L. SEIPELT-THIEMANN

community for their own use. However, as noted in previous

research (Venville & Treagust, 1997; Orgill & Bodner, 2004),

analogies can be at best helpful, but at least, confusing and/or

harmful to the learning experience. To address this issue, the

analogies were evaluated by upper division undergraduates and

master’s students for two cycles of the course (two years). In-

terest, engagement, understanding and confusion were assessed

on a Likert scale (1 - 5) by students prior to the analogy (Figure

2(A)) and the change in interest, engagement, understanding,

and confusion was self-reported following the analogies (Fig-

ures 2(B) and 3). Pre-analogy interest for all analogies ranged

from a mean of 3.23 to 3.57 out of 5. For engagement, the

(A) (B)

Figure 2.

Student Assessment. Mean values of interest, engagement, understanding, and confusion relating to allele dominance (A) Prior

to analogies. Scoring was 1 - 5 with 1 being least and 5 being most and (B) Change following analogies. Scoring was −1 to +1

with −1 indicating decrease, 0 indicating no change, and +1 indicating an increase. n = 36.

(A) (B)

Figure 3.

Overview of student-reported change following analogies. Student decreases, no changes, and increases are represented as stacked columns showing

the proportion or percentage of total students having increased, decreased, and no change in (A) Interest; (B) Engagement; (C) Understanding; and (D)

Confusion. n = 36.

R. L. SEIPELT-THIEMANN

average pre-analogy scores ranged from 3.0 to 3.32. The under-

standing pre-analogy mean scores had a range of 2.82 to 3.62.

Self-reported confusion prior to analogy for all analogies

ranged from 1.85 to 2.43.

General observations and trends, rather than statistical anal-

yses, are reported here, first because there is little statistical

power in small observation samples, and second, it is of interest

to observe how individual students within the pool reflected on

their own learning and analogy use. To highlight this, the data

for change in interest, engagement, understanding, and confu-

sion are presented as stacked columns where each student’s

response within the pool is visible (Figure 3). Following the

analogy, students reported little to no decreases in interest,

engagement, or understanding and little to no increases in con-

fusion (Figures 3(A)-(D)). Approximately half of all students

noted an increase in interest and engagement for all analogies

(Figures 3(A) and (B)), while most students reported an in-

crease in understanding for three of the five analogies (Figure

3(C)). The self-reported change in confusion differed the most

of all measurements, with the analogy for inappropriate expres-

sion being ranked as least helpful and the analogy for increased

activity being rated as most helpful (data not shown).

Discussion

Science students and teachers commonly use analogies inside

and outside the classroom to bridge the gap between an idea

they understand and a similar new idea or concept. In particular,

analogies for genetics, molecular biology, and biochemistry

concepts, which are highly abstract, can benefit students’ un-

derstanding. The purpose of this project was to construct and

evaluate analogies of molecular mechanisms to help gain a

greater understanding of mutant allele dominance in human

genetic disease. Five analogies for five distinct molecular

mechanisms were tested with upper-level undergraduates and

masters-level students in two cycles of a human genetics course

(n = 36). All were positively reviewed by the majority of stu-

dents. Extending the experiences with other examples and

thought-provoking problems, as noted in the section above, in

addition to having students identify areas in which the analogy

breaks down, will be helpful to those students who may not

have benefited from the initial analogy. These analogies may be

particularly useful for those instructors who are moving to-

wards a curriculum that is centered on genetic and phenotypic

variation, molecular consequences, and genomics, as proposed

for different educational audiences by Dougherty (2009) and

Redfield (2012), as they help visually illustrate molecular con-

nections among genes, heterozygosity, biochemistry, genotype,

and phenotype in the human.

Acknowledgements and Supplementary Material

RLST thanks Dr. Michael Rutledge and Ms. Chatoria Kent

for their helpful comments. RSLT will gladly share the intro-

ductory powerpoint slides. Please contact her by email at re-

[email protected].

REFERENCES

Becker, M. A., Meyer, L. J., & Seegmiller, J. E. (1973). Gout with

purine overproduction due to increased phosphoribosyl phosphate

synthetase activity. American Journal of Medicine, 55, 232-242.

doi:10.1016/0002-9343(73)90174-5

Busciglio, R. (2010). Lucy candy 3.

http://www.youtube.com/watch?v=0YGF5R9i53A

De Klein, A., Van Kessel, A. G., Grosveld, G., Bartram, C. R., Hage-

meijer, A., Bootsma, D., Spurr, N. K., Heisterkamp, N., Groffen, J.,

& Stephenson, J. R. (1982). A cellular oncogene is translocated to

the Philadelphia chromosome in chronic myelocytic leukaemia. Na-

ture, 300, 765-767. doi:10.1038/300765a0

Dougherty, M. J. (2009). Closing the gap: Inverting the genetics cur-

riculum to ensure an informed public. The American Journal of Hu-

man Genetics, 85, 6-12. doi:10.1016/j.ajhg.2009.05.010

Gericke, N. M., & Hagberg, M. (2007). Definition of historical models

of gene function and their relation to students’ understanding of ge-

netics. Science & Education, 16, 849-881.

doi:10.1007/s11191-006-9064-4

Glynn, S. M. (1995). Conceptual bridges: Using analogies to explain

scientific concepts. The Science Teacher, 62, 25-27.

Glynn, S. M. (2007). Methods and strategies: The Teaching-with-

analogies model. Science and Children, 44, 52-55.

Glynn, S. M. (2008). Making science concepts meaningful to students:

Teaching with analogies. In S. Mikelskis-Seifert, U. Ringelband, &

M. Brückmann (Eds.), Four decades of research in science educa-

tion: From curriculum development to quality improvement (pp. 113-

125). Münster: Waxmann.

Herrick, J. B. (1910). Peculiar elongated and sickle-shaped red blood

corpuscles in a case of severe anemia. Archives of Internal Medicine,

6, 517-521.

Korkko, J., Ritvaniemi, P., Haataja, L., Kaariainen, H., Kivirikko, K. I.,

Prockop, D. J., & Ala-Kokko, L. (1993). Mutation in type II procol-

lagen (COL2A1) that substitutes aspartate for glycine alpha-I-67 and

that causes cataracts and retinal detachment: Evidence for molecular

heterogeneity in the Wagner syndrome and the Stickler syndrome

(arthro-ophthalmopathy). The American Journal of Human Genetics,

53, 55-61.

Oliva, J. M., Axcarate, P., & Navarrete, A. (2007). Teaching models in

the use of analogies as a resource in the science classroom. Interna-

tional Journal of Science Education, 2 9, 45-66.

doi:10.1080/09500690600708444

Online Mendelian Inheritance in Man (2012). MIM Number: {108300}.

Baltimore, MD: Johns Hopkins University. URL (last checked 20

January 2012). http://omim.org/

Online Mendelian Inheritance in Man (2012). MIM Number: {141900}.

Baltimore, MD: Johns Hopkins University. URL (last checked 6 June

2012). http://omim.org/

Online Mendelian Inheritance in Man (2011). MIM Number: {166210}.

Baltimore, MD: Johns Hopkins University. URL (last checked 6 Oc-

tober 2011). http://omim.org/

Online Mendelian Inheritance in Man (2012). MIM Number: {300661}.

Baltimore, MD: Johns Hopkins University. URL (last checked 20

April 2012). http://omim.org/

Online Mendelian Inheritance in Man (2012). MIM Number: {608232}.

Baltimore, MD: Johns Hopkins University. URL (last checked 27

July 2012). http://omim.org/

Oppenheimer, J., Pugh, M., Carroll, B. Jr. (Writers), & Asher, W. (Di-

rector) (1952). Job switching [39]. In D. Arnaz (Producer), I love

Lucy. Hollywood, CA: Columbia Broadcasting System.

Orgill, M. and Bodner, G. (2004). What research tells us about using

analogies to teach chemistry. Chemistry Education: Research and

Practice, 5, 15-32.

Richards, A. J., Baguley, D. M., Yates, J. R. W., Lane, C., Nicol, M.,

Harper, P. S., Scott, J. D., & Snead, M. P. (2000). Variation in the

vitreous phenotype of Stickler syndrome can be caused by different

amino acid substitutions in the X position of the type II collagen

Gly-X-Y triple helix. The American Journal of Human Genetics, 67,

1083-1094. doi:10.1086/321189

Redfield, R. J. (2012). “Why do we have to learn this stuff?”—A new

genetics for 21st century students. PLOS Biology, 1 0 , e1001356.

doi:10.1371/journal.pbio.1001356

Smith, M. U., & Adkison, L. R. (2010). Updating the model definition

of the gene in the modern genomic era with implications for instruc-

tion. Science & Education, 19, 1-20. doi:10.1007/s11191-008-9161-7

Tibell, L. E. A., & Rundgren, C.-J. (2010). Educational challenges of

888

R. L. SEIPELT-THIEMANN

molecular life science characteristics and implications for education

and research. CBE Life Sciences Education, 9, 25-33.

doi:10.1187/cbe.08-09-0055

Venville, G. J., & Teagust, D. F. (1997). Analogies in biology educa-

tion: A contentious issue. The American Biology Teacher, 59, 282-

287. doi:10.2307/4450309

Williams, C. J., & Prockop, D. J. (1983). Synthesis and processing of a

type I procollagen containing shortened pro-alpha-1(I) chains by fi-

broblasts from a patient with osteogenesis imperfecta. The Journal of

Biological Chemistry, 258, 5915-5921.