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Perspective

Why Do We Have to Learn This Stuff? A New


Genetics for 21st Century Students
Rosemary J. Redfield*
Department of Zoology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

generation. Next came the evidence that phenotypes in crosses, conversations at


genes are on chromosomes, followed by office hours and tutorials revealed that
the light-microscopy view of chromosome they had only very unconventional ideas
behaviour in meiosis. Analysis of genetic about how gene products interact to
crosses then gradually revealed all the determine phenotype (see Box 2: The
standard conceptslinkage and crossing Dominance Problem). And although they
over, gene mapping, sex linkage, epistasis, could reproduce the stages of meiosis, map
chromosome changes. Some instructors genes in three-factor crosses, and diagram
supplemented these topics with a smatter- meiotic recombination in complex inver-
ing of molecular genetics, but serious sion-heterozygotes, most had no idea how
treatment was left to a later course using or why homologous chromosomes pair
the second half of the textbook. The term and recombine. Although not all instruc-
finished with a few lectures on the basic tors report these problems, similar persis-
theories of population and quantitative tent misconceptions have been described
genetics as established in the mid-20th by Smith and Knight [4]).
Several years ago, our biology program century. The committee responsible for develop-
decided to develop a new second-year This historical presentation has a long- ing our new course thought that the
Fundamentals of Genetics course to established rationale [3]. Having students historical approach was making genetic
replace the third-year course that was follow in the intellectual footsteps of the analysis harder for our students to learn,
our legacy from David Suzuki and Tony great geneticists should make the concepts not easier. Understanding even the simplest
Griffiths. Although our new syllabus easier to learn because it mirrors the cross requires combining inferences about
radically altered how the core concepts questions students will naturally ask. two complex processeshow genetic ele-
are taught, I now think the changes were Students are also expected to gain much- ments are inherited through meiosis and
much too conservative because wed needed practice in scientific thinking and a mating, and how these elements act and
ignored how drastically the role of genetics better appreciation of the nature of interact to cause the phenotypic differences
has changed. Below I first describe the scientific knowledge because each new seen in the parents and the progeny.
problems we originally identified and how principle is necessitated by experimental Pioneer geneticists treated these processes
we addressed them, and then consider the evidence. And finally, seeing how genetic as black boxes whose rules they deduced,
bigger problem of moving introductory analysis has revealed the mechanisms of but our students appeared to avoid this
genetics courses into the 21st century. inheritance should show students its value challenge by simply memorizing the rules
in dissecting other biological phenomena. and problem-solving rubrics that well-
Unfortunately, this wasnt working as meaning instructors provided. Compound-
The Canon
planned; although students learned to ing the difficulty, classic experiments often
Our old course followed the canonical solve our genetic analysis problems, their require students to also understand com-
textbook structure, using genetic analysis ability to think scientifically didnt notice- plex experimental details unrelated to the
(see Box 1 for Glossary) to teach the ably improve and they didnt seem to principle being taught (e.g., the use of
principles of transmission genetics, with understand much genetics. For example, pneumococcal transformation to show that
the history of genetics providing the although most students test results showed DNA is the genetic material). There was no
organizing framework (see, for example, that they could predict and interpret time or resources for a formal study (the
[1,2]). It began with Mendels experiments
and the principles they revealedpheno- Citation: Redfield RJ (2012) Why Do We Have to Learn This Stuff? A New Genetics for 21st Century
types are determined by genes whose Students. PLoS Biol 10(7): e1001356. doi:10.1371/journal.pbio.1001356
alleles pass unchanged through the gener- Series Editor: Cheryl A. Kerfeld, University of California Berkeley/Joint Genome Institute, United States of
ations; alleles are dominant or recessive; America
pairs of alleles separate into gametes and Published July 3, 2012
form new combinations in each new Copyright: 2012 Rosemary J. Redfield. This is an open-access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.
The Perspective section provides experts with a Funding: The author received no specific funding for this work.
forum to comment on topical or controversial issues
of broad interest. Competing Interests: The author has declared that no competing interests exist.
* E-mail: redfield@zoology.ubc.ca

PLoS Biology | www.plosbiology.org 1 July 2012 | Volume 10 | Issue 7 | e1001356


Box 1. Glossary mechanism. Instead of memorizing the
stages seen under a light microscope,
Epigenetic: heritable differences due to reversible modification of DNA rather students consider first the problems mitosis
than to changes in DNA sequence. and meiosis must solve (how to get the
right chromosomes into the daughter cells)
Epistasis: change in phenotype caused when different alleles of one gene alter and then their molecular solutions (cohe-
the effects of alleles of another gene. sin, separase, spindle fiber tension, and
especially the role that sequence recogni-
Exome: the expressed part of the genome, all the exon sequences. tion by invading DNA strands plays in
Genetic analysis: using the phenotypic outcomes of genetic crosses to make homolog pairing and crossing over). The
inferences about inheritance and gene function. effects of independent chromosome assort-
ment and of crossing-over are explored by
Homologous chromosomes: chromosomes carrying different versions of the first explicitly working out the genotypes of
same genes in the same order. Usually these DNA sequences differ by only about the gametes produced by meiosis, and
0.1%. then using Punnett squares to represent
how gametes come together randomly in
Haplosufficiency: a condition where having one functional and one nonfunc- mating. Once these blocks have solidified
tional version of a gene provides sufficient gene activity to give a normal the fundamental principles of phenotypes
phenotype. and inheritance, genetic analysis is used to
teach the more complex concepts.
Inversion-heterozygote: A situation where one of a pair of homologous
chromosomes has an inversion that reverses the order of genes in one segment.
The two chromosomes must contort to pair the inverted part with its The Canon Is Past Its Sell-By
homologous sequences. Date
Quantitative genetics: Analysis of the contributions of multiple, often We were all proud of the new courses
hypothetical, genes to a single phenotype. syllabus, and it was only when I taught the
first section last year that I realized how
Tetrad analysis: using a micromanipulator to separate the four spores or obsolete the contents are. Id introduced a
gametes produced by a single meiosis and then analyzing their genotypes. brief Genetics in the News segment at
the start of each class; my intent was to
Three-factor cross: a cross whose partners differ at three different positions on show students the relevance of what I was
a single chromosome; typically used to map the relative locations of the genes. teaching them, but the torrent of genetics
news I was sorting through instead showed
first validated tools for assessing genetics mating, free from the confusion of pheno- me its irrelevance.
learning were just becoming available types. Meiosis is the biggest obstacle for Our goal in designing the course had
[5,6]), so we went ahead and put our best most genetics students, and this block been to make students competent in the
ideas into the new course. emphasizes its function and molecular standard principles of transmission genetics,
Our new syllabus addresses these prob-
lems by dispensing with the historical Box 2. The Dominance Problem
approach and by deferring analysis of
crosses until after the underlying processes Mendels concept of dominance leaves students deeply confused about both its
have been explicated. Thus, our course meaning and its causes. Most students mistakenly believe that alleles are
begins not with Mendel but with two intrinsically either dominant or recessive, as did Mendel. But dominance is a
independent blocks, first a three-week relationship between allelesone allele is dominant to another if its homozygous
block on gene function (how genotype phenotype is also seen in the heterozygote. Mendels error was reasonable
determines phenotype), and then a two- because he had limited his analyses to allele pairs, but the convenient but
week block on inheritance. Our second- erroneous A/a representation he introduced has propagated his misconception
through textbooks and homework problems.
year students come to us knowing the
basics of molecular biology, but they Students also mistakenly think that dominant/recessive relationships are the
havent thought about how differences in norm. This is largely because almost all the alleles they see in their genetics
DNA cause differences in phenotypes, course are presented in dominant/recessive pairs, with alternatives presented
especially not in diploids (hence their deep only as variants of or exceptions to dominance (codominance and incomplete
confusion about dominance). Block 1 dominance). This problem also has been reinforced by generations of
teaches how diploid phenotypes arise from geneticists, who, like Mendel, have preferred to work with alleles showing
homozygous and heterozygous differences clear-cut phenotypic differences. This issue is becoming increasingly important as
in genes with various simple and/or we uncover the genetic underpinnings of natural phenotypic variation, very little
interacting functions. Students first en- of which shows classical dominance.
counter dominance and epistasis here, not
as abstractions but as predictable conse- Finally, even though most modern textbooks explain that dominance is usually
caused by haplosufficiency, informal questioning of students in our upper-level
quences of the metabolic and regulatory
genetics course reveals that most still have no idea what makes one allele dominant
interactions between functional and non-
to another. They have a hard time even understanding the question, and when
functional proteins. In Block 2, students pressed they typically speculate that dominant alleles must actively turn off their
learn to follow DNA sequence differences recessive partners, perhaps by acting as repressors or via epigenetic effects.
and named alleles through meiosis and

PLoS Biology | www.plosbiology.org 2 July 2012 | Volume 10 | Issue 7 | e1001356


the promised $1000 genome sequence will
Box 3. Headlines from a Google News Search on March 19, 2012 be cheaper than most MRI scans. By the
time our students become parents, stan-
N First Complete Full Genetic Map of Promising Energy Crop (Mapping the dard obstetrics packages may include
genome of Miscanthus.) sequencing the babys genome.
N New Genetic Test Predicts Better Egg Production for Women with Poor Ovarian A good place to see these and other
Reserve (Heterozygosity for the fragile-X gene improves fertility.) changes is headline newsBox 3 gives
N DNA Electronics Partners with geneOnyx to Offer Genalysis (Personal DNA some high-ranking hits from a recent
Google News search for genetics. These
testing for the beauty industry.)
N Geneticists Personalized Medicine Study Focuses on Himself (How Mike raise complex questions, both personal
and societal, that our students will need to
Snyder predicted and tracked his own diabetes.)
answer. Is genetic testing a wise thing to
N Genetic Tests to Generate $25 Billion a Year, UnitedHealth Says (Should you
do? Is it a sound financial investment?
invest now?)
Should I have full access to my genetic
N International Conference on Consanguineous Marriage Continues (A Middle-
information? Should my insurer and my
East country hopes to reduce genetic problems caused by inbreeding.)
employer? Should athletes be tested for
N Prehistoric Icemans DNA Reveals Startling Secrets (He was just like us!) genetic modifications (gene doping)? Is
N Genetic Testings Growth Raises Legal and Ethical Concerns (Will these outweigh it ethical to DNA-fingerprint all convicted
the expected savings in health-care costs?) criminals? All suspects? Did my genes
N Genetics Not Education Drives Investor Behaviour (Heritability is 50% in a make me gay? Are genetically modified
identical-twin study.) foods safe? Are cloned animals ethical?
N Gorillas More Related to People Than Thought, Genome Says (15% of gorilla How different are human races, and how
different are we all from chimpanzees and
genes are closer to humans than to chimps.)
gorillas?
The nature of genetics research has
but we had totally failed to consider whether Perhaps the biggest change is the rise of changed too. For our own and other
this is really what our students need to know. direct-to-consumer genetic and genomics species, emphasis has shifted from labora-
In fact, wed been failing to do this for many services. (These services arent only for tory mutations to natural genetic and
yearscomplaining about students forget- people: $69.99 plus a cheek swab will tell phenotypic variation. Humans are rapidly
ting everything wed taught when the course you the ancestry of your mutt, and $19.50 becoming the best-understood genetic
ended, but never once thinking that this plus a feather will tell you whether your system; there are many more complete
might be (i) our fault for teaching them parrot is Polly or Paul.) As of October genome sequences for humans than for
material they would never use and (ii) 2011, more than 125,000 customers of any other species, and more detailed
correctable by making the course content 23andMe have signed up for personal surveys of natural variation [7,8]. This
more relevant. Fifty years ago this wouldnt genotyping at a million SNP positions and natural variation used to be largely out of
have been a big oversight, but now genes are access to 23andMes excellent interpretive reach, only investigated using the abstrac-
everywhere, sometimes trivially (the DNA resources. Direct-to-consumer exome se- tions of classical quantitative genetics, but
of Toyota), but more often with serious quencing is already available as a pilot genome-wide association studies are now
implications for personal and public life. venture ($999 for 70-fold coverage), and able to find genes that affect just about any

Box 4. Suggested Syllabus for a 21st Century Genetics Course

N Personal genomics
N Natural genetic variation in populations (humans and others)
N Structure and function of genes and chromosomes
N Genetic variation arises by mutation
N Genetic variation and evolution (selection for function, phylogeny, homologs, gene families)
N How genes affect phenotypes: pathways, regulatory interactions, heterozygosity, dominance effects (several classes)
N Genetic variation also arises by chromosome reassortment and homologous recombination
N Mitosis and meiosis: mechanisms and genetic consequences (several classes)
N Mating: mechanisms and genetic consequences
N Linkage and sex linkage
N Genetic analysis: investigating gene action using inheritance of simple (Mendelian) alleles and phenotypes in crosses and
pedigrees (several classes)
N Organelle genetics
N Epigenetic inheritance
N Genome structure, function and evolution; causes and consequences of chromosomal changes (several classes)
N Phenotypic effects of natural genetic differences, heritability
N Genome-wide association studies and related studies linking genes to phenotypes (several classes)
N Genetics of cancer; inheritance of alleles affecting risk

PLoS Biology | www.plosbiology.org 3 July 2012 | Volume 10 | Issue 7 | e1001356


phenotype. One consequence is that genes evolve, and how they cause differences in textbook. Although most of the topics I
are now studied in the context of popula- phenotypefollowed by how genetic dif- would introduce are at least touched on by
tions, since crosses cant distinguish the ferences are inherited and recombined. current textbooks, the material is not very
small phenotypic effects typical of natural With this under their belts, students are useful because its in advanced chapters,
variation. Finally, evolution is now explic- ready for a taste of genetic analysis, maybe not integrated into the core material.
itly intertwined with genetics at every just enough to whet their appetites for an Textbook publishers are very conservative,
point, both firmly embedded in differences advanced course on genetic methods. The and even books with an ostensibly molec-
between DNA sequences. Sequence con- course then returns to natural genetic ular focus usually leave the canon intact.
servation tells us which parts of genes are variation, now considering how it can be Online resources may be able to fill the
essential for function, and analysis of gene studied, and how to interpret the results. gap, but finding and modifying them will
families tells us how functions change. Nothing is taught as a black box still be a lot of work.
Changes in the student population have everything is presented in the context of As a first step, geneticists need to step
made the canon even less relevant. its molecular underpinnings. back from the current curriculum and
Genetics used to be an advanced elective This radical a change will encounter lots decide what 21st century students really
for intellectually ambitious students, but of obstacles. For many geneticists the most need to know about genes and inheritance.
most biology programs now require it of upsetting change will be the demotion of These decisions should be based on how
everyone. Many of these students will genetic analysis from its reigning place in students will use what they learn, and not
never take another genetics course, much the curriculum. Genetic analysis used to on what we as geneticists value. Then we
less engage in genetics research. On the be the most powerful tool for understand- can develop specific learning goalslists
other hand, students destined for profes- ing how organisms work, and thus the best of skills we want students to gain from our
sional programs in the health sciences skill we could give our students, but its teaching. Only then will we be ready to
need much more genetics than they used research role has been largely supplanted develop a syllabus, and to create the
to, since theyll increasingly be requesting by molecular methods. Cuts to genetic textbooks, assessment tools, and validation
genetic tests and explaining the results to analysis also threaten the problem-based tools well need. At the same time, we
their patients. Fortunately, the genetics learning that has been a hallmark of should be promoting parallel changes at
theyll need is just a slightly more sophis- genetics courses. Genetics instructors have earlier levels; the brief time high school
ticated version of what the others will need all devoted time to developing problems and first-year university students devote to
in their daily livesa solid understanding that replicate those arising in real genetics genetics shouldnt be wasted on Mendels
of how genes influence phenotypes, of research labs, and a major feature in
natural genetic variation, and of the laws and Punnett squares.
textbook choice is the quantity and quality I expect that just reading this article will
mechanism of heredity.
of the end-of-chapter problems. have raised the hackles of many readers
Instructors are certainly not unaware of
Other cuts will be less traumatic. Our whose favourite topics I would cut.
these changes, and many have modified
students will probably never need to do a Procrastination is attractiveif we wait
what they teach to include as much new
3-factor cross, except maybe in an outdat- long enough, maybe the pace of change
material as possible. But patching new
ed genetics laboratory course, nor to will slow, the issues will become clearer,
material onto our outdated genetics canon
analyze phenotypic ratios of progeny, once and traditionalist colleagues will retire. As
fails to address its fundamental obsoles-
one of the pillars of genetics [1]. long as we remain comfortable with
cence. Its time to make a fresh start.
Theres also little justification for retaining teaching largely irrelevant material, we
haploid genetics, fungal genetics, tetrad dont have to worry about changing it.
A Clean Break with the Canon analysis, and classical somatic-cell genetics But if we want to make the genetics we
Box 4 gives a suggested syllabus for a in an introductory genetics course. Classi- teach genuinely useful to our students, we
21st century genetics course. It begins with cal bacterial genetics (conjugation, trans- need to start the process now.
a human focus, introducing personal duction, transformation) should go too To get the discussion going, please consider
genomics and our natural genetic varia- Im a bacterial geneticist, so trust me on describing your experiences and suggestions in the
tion. Students then learn about the this one. Comments section. (Editors note: Click on the
underlying molecular explanationshow One of the biggest obstacles is purely Comments tab under the title of the article.)
differences in DNA sequences arise and practicalthe lack of any suitable

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PLoS Biology | www.plosbiology.org 4 July 2012 | Volume 10 | Issue 7 | e1001356

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