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Learning molecular biology involves using visual representations to communicate ideas about largely unobservable biological processes and molecules. Genes and gene expression cannot be directly visualized, but students are expected to learn and understand these and related concepts. Theoretically, textbook illustrations should help learners master such concepts, but how are genes and other DNA-linked concepts illustrated for learners? We examined all DNA-related images found in 12 undergraduate biology textbooks to better understand what biology students encounter when learning concepts related to DNA. Our analysis revealed a wide array of DNA images that were used to design a new visual framework, the DNA Landscape, which we applied to more than 2000 images from common introductory and advanced biology textbooks. All DNA illustrations could be placed on the landscape framework, but certain positions were more common than others. We mapped figures about "gene expression" and "meiosis" onto the landscape framework to explore how these challenging topics are illustrated for learners, aligning these outcomes with the research literature to showcase how the overuse of certain representations may hinder, instead of help, learning. The DNA Landscape is a tool to promote research on visual literacy and to guide new learning activities for molecular biology.

The process of meiosis is an essential topic that secondary and postsecondary students struggle with. The important meiosis-related concepts of homology, ploidy, and segregation can be described using the DNA Triangle framework, which connects them to the multidimensional nature of DNA (chromosomal, molecular, and informational levels). We have previously established that undergraduate biology students typically fail to describe and/or link appropriate levels to their explanations of meiosis. We hypothesize that students' understanding mirrors the resources they are given – in other words, textbook figures often lack many of the important connections that experts include when talking about meiosis. Prior work showed that text in meiosis chapters typically fails to include many concepts that experts consider important, so we examined how textbook figures present meiosis concepts. We found that almost all textbook representations include the chromosomal level of DNA, but few include the other levels, even to illustrate concepts that are rooted in informational and/or molecular levels. In particular, the molecular level of DNA was absent from nearly all introductory textbook figures examined, and the informational level was seldom depicted in mid/upper-level textbook figures. The previously established deficits in text portions of textbooks are clearly not compensated by their accompanying illustrations.

Concepts of molecular biology and genetics are difficult for many biology undergraduate students to master yet are crucial for deep understanding of how life works. By asking students to draw their ideas, we attempted to uncover the mental models about genes and gene expression held by biology students (n = 23) and experts (n = 18) using semistructured interviews. A large divide was identified between novice and expert conceptions. While experts typically drew box-and-line representations and thought about genes as regions of DNA that were used to encode products, students typically drew whole chromosomes rather than focusing on gene structure and conflated gene expression with simple phenotypic outcomes. Experts universally described gene expression as a set of molecular processes involving transcription and translation, whereas students often associated gene expression with Punnett squares and phenotypic outcomes. Follow-up survey data containing a ranking question confirmed students’ alignment of their mental models with the images uncovered during interviews (n = 156 undergraduate biology students) and indicated that Advanced students demonstrate a shift toward expert-like thinking. An analysis of 14 commonly used biology textbooks did not show any relationship between Punnett squares and discussions of gene expression, so it is doubtful students’ ideas originate directly from textbook reading assignments. Our findings add to the literature about mechanistic reasoning abilities of learners and provide new insights into how biology students think about genes and gene expression.

Many biology students struggle to learn about the process of meiosis and have particular difficulty understanding the molecular basis of crossing over and the importance of homologous pairing for proper segregation. To help students overcome these challenges, we designed an activity that uses a newly developed Chromosome Connections Kit® from 3-D Molecular Designs to allow learners to explore meiosis at the molecular level. We took a backwards design approach in constructing an effective classroom activity. We developed evidence-based learning objectives and designed a crossing over activity that targets students' misconceptions and key concepts about meiosis. Assessment questions were designed based on the learning objectives and common student misconceptions. The activity consists of three parts: an interactive introductory video, a model-based activity, and reflection questions. The activity was first beta-tested with a small number of students and revised based on feedback. The revised activity was deployed in a mid-level Cell and Molecular Biology course. Analysis of pre-/post-assessment data from students who completed the activity (n = 83) showed strong learning gains on concepts related to ploidy, homology, segregation, and the mechanism and purpose of crossing over. Additionally, students who participated in the activity outperformed nonparticipants on a Genetics assessment about meiosis the following semester.

The essence of molecular biology education lies in understanding of gene expression, with subtopics including the central dogma processes, such as transcription and translation. While these concepts are core to the discipline, they are also notoriously difficult for students to learn, probably because they cannot be directly observed. While nearly all active learning strategies have been shown to improve learning compared with passive lectures, little has been done to compare different types of active learning. We hypothesized that physical models of central dogma processes would be especially helpful for learning, because they provide a resource that students can see, touch, and manipulate while trying to build their knowledge. For students enrolled in an entirely active-learning-based Cell & Molecular Biology course, we examined whether model-based activities were more effective than non-model based activities. To test their understanding at the beginning and end of the semester, we employed the multiple-select Central Dogma Concept Inventory (CDCI). Each student acted as their own control, as all students engaged in all lessons yet some questions related to model-based activities and some related to clicker questions, group problem-solving, and other non-model-based activities. While all students demonstrated learning gains on both types of question, they showed much higher learning gains on model-based questions. Examining their selected answers in detail showed that while higher performing students were prompted to refine their already-good mental models to be even better, lower performing students were able to construct new knowledge that was much more consistent with an expert's understanding. © 2018 The Authors. Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology., 46(5):435-444, 2018.

The essence of molecular biology education lies in understanding of gene expression, with subtopics including the central dogma processes, such as transcription and translation. While these concepts are core to the discipline, they are also notoriously difficult for students to learn, probably because they cannot be directly observed. While nearly all active learning strategies have been shown to improve learning compared with passive lectures, little has been done to compare different types of active learning. We hypothesized that physical models of central dogma processes would be especially helpful for learning, because they provide a resource that students can see, touch, and manipulate while trying to build their knowledge. For students enrolled in an entirely active‐learning‐based Cell & Molecular Biology course, we examined whether model‐based activities were more effective than non‐model based activities. To test their understanding at the beginning and end of the semester, we employed the multiple‐select Central Dogma Concept Inventory (CDCI). Each student acted as their own control, as all students engaged in all lessons yet some questions related to model‐based activities and some related to clicker questions, group problem‐solving, and other non‐model‐based activities. While all students demonstrated learning gains on both types of question, they showed much higher learning gains on model‐based questions. Examining their selected answers in detail showed that while higher performing students were prompted to refine their already‐good mental models to be even better, lower performing students were able to construct new knowledge that was much more consistent with an expert's understanding. © 2018 The Authors. Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology., 46(5):435–444, 2018.

Biology education relies heavily on visual representations, many of which contain arrow symbols. Many different styles of arrows are used, with no correlation to their underlying meaning. This creates a problem for students, who struggle to interpret and learn from figures containing arrows in biology., In this article, we begin to unpack the phenomenon of representational competence by exploring how arrow symbols are used in introductory biology textbook figures. Out of 1214 figures in an introductory biology textbook, 632 (52%) of them contained arrows that were used to represent many different concepts or processes. Analysis of these figures revealed little correlation between arrow style and meaning. A more focused study of 86 figures containing 230 arrows from a second textbook showed the same pattern of inconsistency. Interviews with undergraduates confirmed that arrows in selected textbook figures were confusing and did not readily convey the information intended by the authors. We also present findings from an online survey in which subjects were asked to infer meaning of different styles of arrows in the absence of context. Few arrow styles had intrinsic meaning to participants, and illustrators did not always use those arrows for the meanings expected by students. Thus, certain styles of arrows triggered confusion and/or incorrect conceptual ideas. We argue that 1) illustrators need to be more clear and consistent when using arrow symbols, 2) instructors need to be cognizant of the level of clarity of representations used during instruction, and 3) instructors should help students learn how to interpret representations containing arrows.

The authors investigated student understanding of central dogma concepts in a variety of settings. They found that students are not primed to think about “information” when presented with the canonical figure of the central dogma and uncovered interesting conceptual misunderstandings about the meaning of the arrows in the representation., The central dogma of molecular biology, a model that has remained intact for decades, describes the transfer of genetic information from DNA to protein though an RNA intermediate. While recent work has illustrated many exceptions to the central dogma, it is still a common model used to describe and study the relationship between genes and protein products. We investigated understanding of central dogma concepts and found that students are not primed to think about information when presented with the canonical figure of the central dogma. We also uncovered conceptual errors in student interpretation of the meaning of the transcription arrow in the central dogma representation; 36% of students (n = 128; all undergraduate levels) described transcription as a chemical conversion of DNA into RNA or suggested that RNA existed before the process of transcription began. Interviews confirm that students with weak conceptual understanding of information flow find inappropriate meaning in the canonical representation of central dogma. Therefore, we suggest that use of this representation during instruction can be counterproductive unless educators are explicit about the underlying meaning.

The DNA triangle integrates three distinct scales at which one can think about DNA. Applying the DNA triangle to topics in meiosis enabled the creation of a new framework for educators and researchers that ties concepts of ploidy, homology, and mechanism of homologous pairing to knowledge about DNA on the chromosomal, molecular, and informational levels., Although instruction on meiosis is repeated many times during the undergraduate curriculum, many students show poor comprehension even as upper-level biology majors. We propose that the difficulty lies in the complexity of understanding DNA, which we explain through a new model, the DNA triangle. The DNA triangle integrates three distinct scales at which one can think about DNA: chromosomal, molecular, and informational. Through analysis of interview and survey data from biology faculty and students through the lens of the DNA triangle, we illustrate important differences in how novices and experts are able to explain the concepts of ploidy, homology, and mechanism of homologous pairing. Similarly, analysis of passages from 16 different biology textbooks shows a large divide between introductory and advanced material, with introductory books omitting explanations of meiosis-linked concepts at the molecular level of DNA. Finally, backed by textbook findings and feedback from biology experts, we show that the DNA triangle can be applied to teaching and learning meiosis. By applying the DNA triangle to topics on meiosis we present a new framework for educators and researchers that ties concepts of ploidy, homology, and mechanism of homologous pairing to knowledge about DNA on the chromosomal, molecular, and informational levels.

Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and in-depth interviews under the theory of knowledge transfer to explain student difficulties with concepts related to chromosomal behavior. In this paper, we show that students typically understand basic chromosome structure but do not activate cognitive resources that would allow them to explain macromolecular phenomena (e.g., homologous pairing during meiosis). To improve understanding of topics related to genetic information flow, we suggest that instructors use pedagogies and activities that prime students for making connections between chromosome structure and cellular processes.

Chromosome structure is confusing to students at all levels, and chromosome behavior during meiosis is a notoriously difficult topic. Undergraduate biology majors are exposed to the process of meiosis numerous times during their presecondary and postsecondary education, yet understanding of key concepts, such as the point at which haploidy is established, does not improve substantially with repeated exposure. Based on student's drawings, 96% of intermediate-level biology majors have unclear or incorrect ideas about meiosis. Students have difficulty diagramming the process of meiosis starting with three unreplicated pairs of chromosomes, and even when they can produce an accurate diagram, they are unclear how to assign the terms “haploid” and “diploid.” We designed an interactive lesson based on constructivist theory to address these issues in a large lecture class. Pretest and posttest scores showed a significant improvement in students' understanding of ploidy compared to a parallel class taught in the traditional way (e.g. using the textbook diagrams). In interviews afterward, those students whose scores improved on exams specifically pointed to the features of the in-class modeling that were deliberately incorporated for that purpose. Biochemistry and Molecular Biology Education Vol. 39, No. 5, pp. 344–351, 2011

This article describes the development of a research-based assessment tool, the Central Dogma Concept Inventory. The instrument consists of 23 multiple-select questions about information flow in molecular biology and gauges conceptual understanding in depth across the undergraduate curriculum., Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select–format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all levels of undergraduate biology. Questions for the Central Dogma Concept Inventory (CDCI) tool were developed and iteratively revised based on student language and review by experts. The ability of the CDCI to discriminate between levels of understanding of the central dogma is supported by field testing (N = 54), and large-scale beta testing (N = 1733). Performance on the assessment increased with experience in biology; scores covered a broad range and showed no ceiling effect, even with senior biology majors, and pre/posttesting of a single class focused on the central dogma showed significant improvement. The multiple-select format reduces the chances of correct answers by random guessing, allows students at different levels to exhibit the extent of their knowledge, and provides deeper insight into the complexity of student thinking on each theme. To date, the CDCI is the first tool dedicated to measuring student thinking about the central dogma of molecular biology, and version 5 is ready to use.

A genome-wide screen for asthma and atopy susceptibility alleles conducted in the Hutterites, a founder population of European descent, reported evidence of linkage with a short tandem repeat polymorphism (STRP) within the type I interferon (IFN) gene cluster on chromosome 9p21. The goal of this study was to identify variation within the IFN gene cluster that influences susceptibility to asthma and atopic phenotypes. We screened approximately 25 kb of sequence, including the flanking sequence of all 15 functional genes and the single coding exon in 12, in Hutterites representing different IFNA-STRP genotypes. We identified 78 polymorphisms, and genotyped 40 of these (in 14 genes) in a large Hutterite pedigree. Modest associations (0.003

Background Asthma is a chronic respiratory disease that often originates in early childhood. Although candidate gene studies have identified many potential asthma susceptibility genes in adult populations, few have studied associations with immune phenotypes in the first year that might be early clinical markers of asthma. Objective The aim of this study was to assess the contribution of genetic variation to cytokine response profiles and atopic phenotypes in the first year of life in the Childhood Origin of Asthma cohort. Methods Two hundred seven European American children participating in the Childhood Origin of Asthma study were genotyped for 61 single nucleotide polymorphisms in 35 genes involved in immune regulation. We examined the relationship between these single nucleotide polymorphisms and PHA-induced cytokine (IL-5, IL-10, IL-13, and IFN-γ) response profiles at birth and at year 1, respiratory syncytial virus–induced wheezing and atopic dermatitis in the first year of life, and total IgE levels, peripheral blood eosinophil counts, and allergic sensitization at age 1 year. The data were analyzed by using censored regression for quantitative measurements and logistic regression for qualitative phenotypes. Results The 237Gly allele of the high-affinity IgE receptor β chain ( FCER1B ) and a silent substitution in the nitric oxide synthase ( NOS)2A gene were associated with reduced IL-13 responses in cord blood ( P = .0025 and P = .0062, respectively). A significant gene-gene interaction between FCER1B 237Gly and NOS2A D346D was detected, with individuals carrying the minor allele for both polymorphisms having the lowest cord blood IL-13 levels. Furthermore, the IL13 110Gln allele showed an association with increased IgE levels at year 1 ( P = .0026), and the colony-stimulating factor 2 ( CSF2 ) 117Thr allele showed an association with a greater increase in IL-5 responses during the first year ( P = .0092). The TGF-β1 ( TGFB1 ) –509T allele was associated with respiratory syncytial virus–related wheezing in the first year ( P = .0005). None of the polymorphisms included in this study were associated with atopic dermatitis during the first year or a positive RAST result at 1 year of age. Conclusion These data suggest that variations in genes involved in immune regulation are associated with biologic and clinical phenotypes in the first year of life that might increase the risk for the subsequent development of childhood asthma.

To avoid problems related to unknown population substructure, association studies may be conducted in founder populations. In such populations, however, the relatedness among individuals may be considerable. Neglecting such correlations among individuals can lead to seriously spurious associations. Here, we propose a method for case-control association studies of binary traits that is suitable for any set of related individuals, provided that their genealogy is known. Although we focus here on large inbred pedigrees, this method may also be used in outbred populations for case-control studies in which some individuals are relatives. We base inference on a quasi-likelihood score (QLS) function and construct a QLS test for allelic association. This approach can be used even when the pedigree structure is far too complex to use an exact-likelihood calculation. We also present an alternative approach to this test, in which we use the known genealogy to derive a correction factor for the case-control association chi2 test. We perform analytical power calculations for each of the two tests by deriving their respective noncentrality parameters. The QLS test is more powerful than the corrected chi2 test in every situation considered. Indeed, under certain regularity conditions, the QLS test is asymptotically the locally most powerful test in a general class of linear tests that includes the corrected chi2 test. The two methods are used to test for associations between three asthma-associated phenotypes and 48 SNPs in 35 candidate genes in the Hutterites. We report a highly significant novel association (P=2.10-6) between atopy and an amino acid polymorphism in the P-selectin gene, detected with the QLS test and also, but less significantly (P=.0014), with the transmission/disequilibrium test.

Serum triglyceride (TG) level is a well-known risk factor for cardiovascular disease, a leading cause of morbidity and mortality in Western countries. Although genome-wide scans for TG have been conducted in several populations, few loci have shown strong evidence for linkage. The Hutterites are a founder population, which practices a communal lifestyle that includes a uniformly high-fat, high-cholesterol diet. We measured serum TG in 485 Hutterites � 14 years old and performed a genome-wide scan to find genetic determinants of the observed variation in TG levels, using mapping methods that take advantage of the extensive inbreeding and linkage disequilibrium (LD) in this single, 1623-member pedigree. We report two highly significant associations with TG levels, alleles at D2S410 on 2q14 (locus P ¼ 5.8 � 10 � 6 , genome-wide P ¼ 0.005) and at IFNA on chromosome 9p21 (locus P ¼ 4.3 � 10 � 5 , genome-wide P ¼ 0.024). In each case, homozygosity at the locus is associated with low TG levels, suggesting that alleles at nearby loci may protect against high TG levels.

SummaryAfter a genomewide screen in the Hutterites was completed, the IL4RA gene was examined as the 16p-linked susceptibility locus for asthma and atopy. Seven known variants and one novel variant, representing all nonsynonymous substitutions in the mature protein, were examined in the Hutterites; on the basis of studies in the Hutterites, outbred white, black, and Hispanic families were genotyped for selected markers. All population samples showed evidence of association to atopy or to asthma (P values .039–.0044 for atopy and .029–.0000061 for asthma), but the alleles or haplotypes showing the strongest evidence differed between the groups. Overall, these data suggest that the IL4RA gene is an atopy- and asthma-susceptibility locus but that variation outside the coding region of the gene influences susceptibility.

Age-related hearing impairment (ARHI), or presbycusis, is a common condition of the elderly that results in significant communication difficulties in daily life. Clinically, it has been defined as a progressive loss of sensitivity to sound, starting at the high frequencies, inability to understand speech, lengthening of the minimum discernable temporal gap in sounds, and a decrease in the ability to filter out background noise. The causes of presbycusis are likely a combination of environmental and genetic factors. Previous research into the genetics of presbycusis has focused solely on hearing as measured by pure-tone thresholds. A few loci have been identified, based on a best ear pure-tone average phenotype, as having a likely role in susceptibility to this type of hearing loss; and GRM7 is the only gene that has achieved genome-wide significance. We examined the association of GRM7 variants identified from the previous study, which used an European cohort with Z-scores based on pure-tone thresholds, in a European–American population from Rochester, NY (N = 687), and used novel phenotypes of presbycusis. In the present study mixed modeling analyses were used to explore the relationship of GRM7 haplotype and SNP genotypes with various measures of auditory perception. Here we show that GRM7 alleles are associated primarily with peripheral measures of hearing loss, and particularly with speech detection in older adults.

Founder populations have been the subjects of complex disease studies because of their decreased genetic heterogeneity, increased linkage disequilibrium and more homogeneous environmental exposures. However, it is possible that disease alleles identified in founder populations may not contribute significantly to susceptibility in outbred populations. In this study we examine the Hutterites, a founder population of European descent, for 103 polymorphisms in 66 genes that are candidates for cardiovascular or inflammatory diseases. We compare the frequencies of alleles at these loci in the Hutterites to their frequencies in outbred European-American populations and test for associations with cardiovascular disease-associated phenotypes in the Hutterites. We show that alleles at these loci are found at similar frequencies in the Hutterites and in outbred populations. In addition, we report associations between 39 alleles or haplotypes and cardiovascular disease phenotypes (P

To the Editor: Most common diseases, such as asthma, type 2 diabetes, bipolar disorder, and cardiovascular disease, are known to have genetic components, but the susceptibility genes have been notoriously difficult to localize and to identify. These complex diseases likely have a large number of genetic and nongenetic risk factors that together have varying effects on phenotype. Many investigators have recommended founder populations for complex-trait mapping, with the expectation that fewer susceptibility alleles will be segregating in these restricted gene pools (Lander and Schork 1994; Wright et al. 1999; Shifman and Darvasi 2001). Some or all individuals in these populations are inbred, but often the exact relationships between all members are either unknown or not taken into account. It is tempting to use such populations for their presumed homogeneity, even in the absence of accurate pedigree information. The failure to take full pedigree information into account can either reduce the power to detect linkage (Dyer et al., in press) or inflate LOD scores (Miano et al. 2000). The failure to account for relatedness among individuals will also affect association studies. In particular, many statistical tests of association are not strictly valid, owing to the lack of true independence between individuals. Nonetheless, such populations have been used widely in association studies (e.g., de Silva et al. 1999; Laprise et al. 2000; Ospina-Duque et al. 2000; Summerhill et al. 2000; Bitti et al. 2001; Hegele et al. 2001), and some authors have even recommended the inclusion of founder populations in case-control studies, owing to their decreased heterogeneity (Shifman and Darvasi 2001). However, the impact that ignoring pedigree relationships has on tests of association has not been evaluated. The Hutterites are an extreme example of a large, complex pedigree with multiple inbreeding loops. We are in the unique position of having complete genealogical information on this 12,903-person, 13-generation pedigree (Abney et al. 2000). Additionally, we have extensive phenotype characterization and a dense microsatellite map (of 568 short-tandem-repeat–polymorphism markers) of ∼750 members of this population, who are descendants of just 64 Hutterite founders (Ober et al. 2000). Thus, we were able to assess the effect that ignoring pedigree information has on statistical tests of association. We performed two separate genomewide scans of association on each of three quantitative phenotypes: serum immunoglobulin E (IgE), serum LDL, and body-mass index (BMI). These phenotypes were chosen to represent quantitative traits associated with diverse complex diseases (asthma, cardiovascular disease, and diabetes, respectively). All phenotypes were adjusted for age and sex and were transformed so that the residuals were approximately normally distributed (Abney et al. 2001). The heritabilities of IgE and BMI were completely accounted for by additive genetic variance, with heritabilities of .63 and .54, respectively; the heritability of LDL had a strong dominance component in addition to additive genetic variance, with a broad heritability of .96 (discussed in detail by Abney et al. [2001]). To estimate the effect that each allele at each locus has on the trait values, we used a statistical test of association, developed specifically for use in large, inbred pedigrees (Ober et al. 2001 [in this issue]). Pedigree structure is taken into account by the use of variance components to model the polygenic background (Abney et al. 2000, 2001). When pedigree structure is ignored, the method is equivalent to a linear regression of the trait on age, sex, and genotype, with a Bonferroni correction applied to the P value for the t test for significance of genotype. In the first scan, we included the variance components and therefore took into account the relatedness between individuals. In the second scan, we did not include any pedigree information (additive and dominance variances were 0). In both scans, the observed P values were adjusted for multiple comparisons, by use of a Bonferroni correction. The two methods yielded dramatically different results. In general, the significance of association with a given marker was considerably inflated when pedigree structure was not included, although in some cases the reverse was true (see fig. 1). Only two loci were among the five most significant results, by both methods, for the three traits (the same marker at 7p21 was associated with IgE, by both methods, and the same marker at 8q12 was associated with LDL, by both methods). In addition, many more loci showed evidence of association when the pedigree structure was not included (see fig. 2). In fact, 10%–22% of all markers appeared to have a strong association (P