Genes, environment, and dyslexia the 2005 Norman Geschwind memorial lecture

This article presents an overview of some methods and results from our continuing studies of genetic and environmental influences on dyslexia, and on individual differences across the normal range that have been conducted over the past 25 years in the Colorado Learning Disabilities Research Center (CLDRC) and in related projects. CLDRC investigators compare the similarities of identical twin pairs who share all their genes and fraternal twins who share half their segregating genes to assess the balance of genetic, shared family environment, and nonshared environment influences on dyslexia and on individual differences across the normal range. We have learned that among the children we have studied in Colorado, group deficits in reading (dyslexia) and individual differences in reading across the normal range are primarily due to genetic influences, and these genetic influences are often shared with some of the same genetic influences on deficits and individual differences in language and ADHD. We have also learned from our molecular-genetic linkage studies that there are regions on several chromosomes likely to contain genes that influence dyslexia. Several specific genes within these regions have been tentatively identified through molecular-genetic association analyses, but much more research is needed to understand the pathways among specific genes, regions of noncoding DNA that regulate the activity of those genes, the brain, and dyslexia. I conclude with a discussion of our research on individual differences in early reading development, on the role of early learning constraints in dyslexia, and on how genetic influences are expressed through their interaction and correlation with the environment.     

Reading disability and chromosome 6p21.3: evaluation of MOG as a candidate gene

Linkage analysis has localized a gene influencing specific reading disability (dyslexia) to 6p21.3. The myelin oligodendrocyte glycoprotein (MOG) gene, which maps to this region, was selected as a candidate. Myelin oligodendrocyte glycoprotein is a membrane protein, a member of the immunoglobin superfamily, that is found on the outermost lamellae of mature myelin. Although the exact function of this protein is unknown, its presence in the central nervous system and the hypothesized relationship between dyslexia and temporal processing rate as well as a suggested relationship with intelligence made this gene a candidate for dyslexia. Analysis of the coding exons and adjacent splice sites in a subset of 22 children with dyslexia from 10 sibships found a missense mutation in exon 4 in 2 of the sibships. This change from the published sequence also occurred in 86 of 96 random controls, making it considerably less frequent in this small sample of individuals with dyslexia. Subsequent typing of this single nucleotide polymorphism (SNP) in 74 nuclear families in which at least one child had reading disability showed no significant difference in frequency from the controls, however. Sib-pair linkage analysis with these families did not show significant linkage with the SNP nor with a separate polymorphic dinucleotide repeat marker in the MOG gene (MOG31/32), but association analysis identified two alleles of MOG31/32 that were associated with reading disability phenotypes with a low level of significance. Thus, although alleles in the MOG gene may be in linkage disequilibrium with a locus that contributes to reading disability, it is unlikely that the MOG gene itself is involved.     

A Conservative Meta-Analysis of Linkage and Linkage-Association Studies of Developmental Dyslexia

Linkage studies of complex phenotypes such as reading ability/disability (developmental dyslexia or reading disorder) and related componential processes, where the effects attributable to individual genes appear to be modest, are critically dependent on the nature and composition of the samples and the phenotypes analyzed. Thus, it might be helpful to consider the results from individual studies collectively so that summative profiles of findings can be considered. To gain an impression of how useful such an approach might be, a conservative meta-analysis based on Fisher's pooled p values approach was performed on regional linkage/association studies of developmental dyslexia and related phenotypes published through early September 2004. The obtained results rank order the findings and stress the need to contextualize the results with more regional linkage/association studies as well as with statistical simulation studies.     

The mathematical strengths and weaknesses of children with dyslexia

This paper reports the findings of two related studies that examined the mathematical strengths and weaknesses of children with dyslexia. In study one, dyslexic children were compared to children without special educational needs on tests that assessed arithmetic fact recall, place value understanding and counting speed. Study two used the same methodology, but matched the dyslexic children with the non‐dyslexic children on a number of factors, including intellectual ability. This excluded the possibility that confounding variables accounted for the differences between the groups in study one. Both studies indicated that the dyslexic children had slower and less accurate number fact recall than the non‐dyslexic children, but had unimpaired place value understanding. The results for counting speed were more equivocal, but there was a trend for the dyslexic children to be slower counters. The results suggest that dyslexia is not normally associated with a general mathematical impairment, but rather an uneven profile of skills. This profile can be explained in terms of the phonological processing weaknesses associated with dyslexia. The finding that dyslexic children have a specific difficulty recalling arithmetic facts suggests that a teaching programme that emphasises mental methods may disadvantage them.     

发展性阅读障碍的神经机制及其对第二语言学习的影响

研究表明拼音文字系统的发展性阅读障碍者与以中文为代表的表意文字系统的发展性阅读障碍者在阅读过程中大脑的激活部位存在差异。关于母语阅读障碍儿童对第二语言学习的影响是近年来发展性阅读障碍研究的热点。双语发展性阅读障碍的理论假设主要有两种语言相互依赖假设和正字法依赖假设。前者认为母语的阅读障碍可以自动迁移到第二语言的学习中;后者认为母语的阅读障碍是否会迁移到第二语言的学习中,要依赖两种语言的正字法特征。我们认为这两种理论不是相互矛盾的,阅读障碍是否会同时出现在两种语言中可能取决于这两种语言是否共用了相同的有缺陷的神经系统。     

基于Java3D的LOD算法的研究与优化

通过对LOD算法的描述与分析,阐述了基于Java3D的LOD技术的应用与实现。并结合具体实例,提出了通过建立Java3D基本共享模型的方法,来减少程序中的冗余重复数据,从而实现LOD算法的优化。     

Identifying students with dyslexia in higher education

An increasing number of students with dyslexia enter higher education. As a result, there is a growing need for standardized diagnosis. Previous research has suggested that a small number of tests may suffice to reliably assess students with dyslexia, but these studies were based on post hoc discriminant analysis, which tends to overestimate the percentage of systematic variance, and were limited to the English language (and the Anglo-Saxon education system). Therefore, we repeated the research in a non-English language (Dutch) and we selected variables on the basis of a prediction analysis. The results of our study confirm that it is not necessary to administer a wide range of tests to diagnose dyslexia in (young) adults. Three tests sufficed: word reading, word spelling and phonological awareness, in line with the proposal that higher education students with dyslexia continue to have specific problems with reading and writing. We also show that a traditional postdiction analysis selects more variables of importance than the prediction analysis. However, these extra variables explain study-specific variance and do not result in more predictive power of the model.     

Developmental dyslexia,neurolinguistic theory and deviations in brain morphology

Although some form of central nervous system involvement is presumed, evidence establishing a relationship between dyslexia and neurological dysfunction has been correlational. Recently, neuroimaging and postmortem studies have begun to provide direct evidence implicating neuropathological structures in dyslexia. This article reviews computed tomography (CT) and magnetic resonance imaging (MRI) studies examining deviations in brain morphology which appear to be associated with neurolinguistic functioning. Methodological and technical issues are discussed. Based on their own and others research, the authors conclude that dyslexics show variations in specific brain regions, namely, reversed or symmetrical plana temporale (LR), smaller insular length bilaterally, and symmetrical frontal regions. Moreover, recent studies by the senior author and colleagues suggest that specific reading tasks are associated with specific variations in brain morphology. Symmetrical frontal widths was related to poorer passage comprehension, and reversed frontal area symmetry was related to poor word attack skills. Though many conceptual and technical issues remain unresolved, neuroimaging procedures appear to provide direct evidence supporting the importance of deviations in normal patterns of brain morphology in dyslexia.     

Using genetics to understand dyslexia

This paper reviews what is currently known about the genetics of dyslexia and shows how genetic studies can help clarify which symptoms are primary and which are secondary in dyslexia. On the genetic side, current evidence supports the view that dyslexia is familial, substantially heritable, and heterogeneous in its genetic mechanisms. At least some forms of familial dyslexia appear to be autosomal dominant, with linkage studies supporting both a major locus on chromosome 15 and genetic heterogeneity. On the symptom side, current evidence supports the view that the primary symptom in dyslexia is a deficit in the phonological coding of written language. This primary symptom likewise appears to be heritable. Recent evidence suggests that the heritable precursor to this written language deficit is a spoken language deficit in the skill of phoneme segmentation and awareness.     

Book Reviews

Increased awareness and improved tests have contributed to the identification of rising numbers of dyslexic students entering higher education in the United Kingdom. Nearly half of these students are not diagnosed until they start their HE courses. Studies of experiences of dyslexic students diagnosed as children exist; however, there is little comparable information on dyslexic students diagnosed as adults.

This qualitative study explores the experiences of six students diagnosed with dyslexia after starting their Masters degrees. Their personal accounts were analysed using thematic analysis. The major themes identified were: ? Distress

? Self-doubt

? Embarrassment

? Frustration

? Relief

? Confidence

? Motivation

The findings revealed that being diagnosed with dyslexia as an adult can be cathartic or devastating depending on the individual’s current emotional status and personality. However, as they develop a deeper understanding of what dyslexia means and how it affects them as individuals, the diagnosis becomes a liberating revelation. Once the label is accepted, the individual can embrace the change in lifestyle that the diagnosis necessitates. This study provides a deeper understanding of the consequences of a late diagnosis and highlights the need for management approaches to be individually tailored to specific needs.     

Visual stress in adults with and without dyslexia

The relationship between dyslexia and visual stress (sometimes known as Meares‐Irlen syndrome) is uncertain. While some theorists have hypothesised an aetiological link between the two conditions, mediated by the magnocellular visual system, at the present time the predominant theories of dyslexia and visual stress see them as distinct, unrelated conditions, a view that has received some support from studies with children. Studies of visual stress in adults are rare, yet recent reports of a high incidence of this phenomenon amongst university students with diagnosed dyslexia call for further investigation of the issue. This study sought to clarify the relationship between visual stress and dyslexia by comparing the reading performance of dyslexic and non‐dyslexic adults with, and without, colour. Degree of susceptibility to visual stress was determined by means of a symptom rating scale. Optimal colour was determined using an Intuitive Colorimeter, which was also employed to assess reading speed under the two experimental conditions. Only the dyslexic students with high visual stress showed significant gains in reading speed when using optimal colour. The use of response to treatment (rather than symptomatology) as a diagnostic criterion for visual stress is questioned, especially when applied to adults, as this may give misleading findings. On the basis of reported symptomatology, students who experience high levels of visual stress are more likely to show improvements in reading rate with optimal colour if they also have dyslexia than if they do not have dyslexia. Although not establishing an aetiological link, these findings imply an interaction between the two conditions with major implications for theory, diagnosis and treatment.     

Experiences of dyslexia and the transition to university: a case study of five students at different stages of study

ABSTRACT

Dyslexia is a common specific learning difficulty. In higher education two models of disability are prevalent, ‘disorder’ and ‘difference’, which each differentially conceptualise dyslexia and the nature of supports required. A lack of research has been undertaken in Ireland regarding students’ experience of dyslexia, and the move from second to third level education. A greater understanding of the challenges encountered is necessary to inform provision of resources to help students with dyslexia excel in higher education. Semi-structured interviews were completed with four undergraduate students and one postgraduate student with a diagnosis of dyslexia to explore their experiences of transitioning into university. Thematic analysis revealed four common themes: dyslexic identity, self-advocacy, transition experiences, and future advice. Various difficulties were identified regarding lack of appropriate academic resources, inconsistencies between supports provided in secondary and third level education, and low self-confidence which serves as a barrier to success. However, strengths including self-directed learning techniques and communication and self-advocacy skills were also evidenced, supporting a ‘difference’ view of dyslexia. The findings highlight the need to re-evaluate the current academic service provisions, in alignment with a model of dyslexia that allows individualisation and enables students, as opposed to disabling them.     

不同家庭结构下的传递不平衡检验的功效(英文)

近年来 ,连锁和关联分析最流行的方法要属传递不平衡检验 (TDT) 而评估TDT的功效和样本大小至关重要 许多文章已讨论此问题 但以前的方法既不精确也不一般化 他们都作了一个简单的假设 ,即每个家庭仅有一个受累子代或两个受累同胞对或非受累同胞对 一个例外是Chen和Deng发展的方法 但他们并没有考虑不同比例的这些家庭对TDT功效和样本大小的影响 本文应用“PC”软件 ,调查了在四个遗传模式下不同的家庭结构对TDT功效的影响 ,考虑以下三种情形 :(1)不同家庭结构的不同比例 ,(2 )标记和易感基因间的不同重组率 ,(3)父母的不同致病状态 调查具有实践意义 因为在实际中 ,更多的是征集到不同结构的家庭 如何设计不同家庭的比例相当重要     

The roles of cognitive and language abilities in predicting decoding and reading comprehension: comparisons of dyslexia and specific language impairment

This study aimed to (a) explore the roles of cognitive and language variables in predicting reading abilities of two groups of individuals with reading disabilities (i.e., dyslexia and specific language impairment) and (b) examine which variable(s) is the most predictive in differentiating two groups. Inclusion/exclusion criteria applied to categorize the two groups yielded a total of 63 participants (n = 44 for the dyslexia; n = 19 for the specific language impairment). A stepwise multiple regression approach was conducted to examine which cognitive and/or language variables made the largest contribution to reading abilities (i.e., Phonetic Decoding Efficiency, Word Attack, Sight Word Efficiency, and Passage Comprehension). Results revealed that there were significant differences in which measures of cognitive and language ability predicted individuals with dyslexia and speech and language impairments reading ability, showing that the cognitive and language variables underlying their difficulty with reading abilities were not the same across the two groups. A discriminant function analysis showed that a measure of Verbal Comprehension, Phonological Awareness, and Phonetic Decoding Efficiency can be used to differentiate the two groups. These findings support the tenet that dyslexia and specific language impairment are two subgroups of reading disabilities and that thorough diagnostic evaluations are needed to differentiate between these two subgroups. Distinctions of this nature are central to determining the type and intensity of language-based interventions.     

Neuropsychological treatment of dyslexia: does type of treatment matter?

In this study, 123 children with a diagnosis of developmental dyslexia were assigned to different treatment groups, either variations of Bakker's intervention program based on the balance model or a control, a specific reading training group. Thorough cognitive and neuropsychological assessment allowed determination of the subtype of dyslexia according to the balance model and the neuropsychological profile with respect to reading and spelling abilities, verbal memory, and phonemic awareness. Characteristics of hemisphere-specific stimulation were systematically manipulated in an effort to shed light on the bases and mechanisms of reading improvement. It was shown that the effects of treatment vary according to type of dyslexia and that the different intervention programs have differential effects on reading-related neuropsychological functions. Since opposite effects can be produced by the same type of treatment in different dyslexia subtypes, the results of the study suggest that accurate classification of subtype on the base of reading and reading-related variables is advantageous for an optimal planning of the therapy.     

Dyslexia assessment in Arabic

Despite advancements in empirical studies of developmental dyslexia, progress on methods of dyslexia assessment have been hampered by ongoing debate concerning diverse issues such as the role and validity of IQ in the assessment process, labelling and definitions ( Miles, 1994 ; Stanovich, 1991, 1992 ). With the emergence of cross-linguistic studies of dyslexia came the realisation that the manifestation of dyslexia is different in different languages ( Goulandris, 2003 ; Smythe, Everatt & Salter, 2004 ). It follows that the assessment of dyslexia should consider specific linguistic features of the language spoken by the individual to be assessed. This paper argues for the need of culture-fair assessment and calls for considerations to be given when assessing monolingual Arabic-speaking individuals with dyslexia which would take into account the specific linguistic feature of the Arabic language.     

Investigating self-regulated study strategies among postsecondary students with and without dyslexia: a diary method study

We investigated the use of self-regulated study strategies among undergraduates with dyslexia by means of extensive web-based diary data, comparing their strategy use to that of matched students without dyslexia who completed the diary in the same period. Additionally, we examined the perceived benefits of using the recorded strategies in both groups, as well as relationships between the recorded strategies and perceived self-efficacy and academic performance. Results indicated that across lecture, individual study, and social study contexts, students with and without dyslexia recorded a comparable, broad range of strategies, yet students with dyslexia seemed to use particular visual and social strategies more consistently than did students without dyslexia. Across the three study contexts, both students with and without dyslexia also perceived the strategies they recorded in the diaries to be quite beneficial, but with particular visual and social strategies seemingly perceived as more helpful by students with dyslexia. Finally, self-regulated study strategies were positively related to perceived self-efficacy and academic performance among the students with dyslexia but not among the students without dyslexia. We discuss the possibility that the diary method used to assess strategy use among students with dyslexia in different study contexts over time was more appropriate for revealing the breadth and value of their strategy repertoire than the decontextualized, one-time questionnaire and interview approaches used in prior work.     

A molecular biological study on identification of common septicemia bacteria using 16s–23s rRNA gene spacer regions

In the search for a rapid and reliable method for identification of bacteria in blood and cerebrospinal fluid , we developed a unified set of primers and used them under polymerase chain reaction(PCR) to amplify the spacer regions between the 16s and 23s genes in the prokaryotic rRNA genetic loci . Spacer regions within these loci showed a significant level of length and sequence polymorphism across most of the species lines. A generic pair of priming sequences was selected from highly conserved sequences in the 16s and 23s genes occurring adjacent to these polymorphic regions. This single set of primers and reaction conditions were used for the amplification of the 16s-23s spacer regions for 61 strains of standard bacteria and corresponding clinical isolates belonging to 20 genera and 27 species, including Listeria, Staphylococcus and Salmonella species, et al. When the spacer amplification products were resolved by electrophoresis, the resulting patterns could be used to distinguish most of the bacteria species within the test group, and the amplification products of the clinical isolates clustered at the standard species level. Some species presenting similar pattern were further analyzed by HinfI or AluI digestion or DNA clone and sequences analysis in order to establish the specific 16s-23s rRNA gene spacer regions map. Analysis of 42 blood specimens from septicemic neonates and 6 CSF specimens from suspected purulent meningitis patients by bacterial culture and PCR-RFLP(Restriction Fregament Length Polymorphism) showed that 15 specimens of blood culture were positive(35.7%) in the 42 septicemic neonates; 27 specimens were positive(64.2%) by PCR, and that the positive rate by PCR was significantly higher than that by blood culture(P<0.01). Among the 6 CSF specimens, one specimen found positive by blood culture was also positive by PCR, two found negative by blood culture showed positive by PCR; all three were S.epidermidis according to the DNA map. One C.neoformans found positive by blood culture showed negative by PCR. The remaining two specimens were both negative by PCR and blood culture. These results indicated that the method of detecting bacterial 16s-23s rRNA spacer regions using PCR and RFLP techniques was rapid, sensitive and specific in the detection of bacterial infections; and so, has very important application in the clinical diagnosis of sepsis in neonates.     

Students' voices: a report of the student view of dyslexia study skills tuition

This article reports research using case studies of 22 university students receiving study skills development funded by the Disabled Student's Allowance at an independent dyslexia consultancy. In‐depth semi‐structured interviews were conducted. The students identify the primary benefits of the tuition as: developing an understanding of dyslexia and specific learning difficulty as part of the process of self‐development; normalising their experiences; and developing their critical analysis and problem‐solving techniques to support the skills needed for studying. The implications for good practice in supporting university students with dyslexia are considered.     

Nonsense passage reading as a diagnostic aid in the study of adult familial dyslexia

We examined Nonsense-Passage oral reading in adults, using data derived from new and previously published studies (Finucci et al 1976, Gross-Glenn et al 1985). Time-scores and error-frequency data are presented for five samples of non-dyslexic readers with a minimum of a high-school education and no childhood history of dyslexia (N=127). Considerable uniformity is demonstrated across these samples, and reading performance of non-dyslexic individuals contrasts sharply with that observed in four samples of adult familial dyslexics. Both affected and compensated-affected dyslexic subjects read the passages significantly more slowly and with more errors than did nondyslexic readers. Results are discussed in relation to the cognitive and neural processes that may underlie this specific reading difficulty in dyslexics. We have found Nonsense-Passage reading to be especially useful in family studies of inherited dyslexia as a means of quantifying oral reading deficits in adults who have learned to compensate for their children reading difficulties.