Nyamweya is a Kenyan scholar who has done many years of research on a diversity of topics
Dyslexia is defined as a learning disability that causes a person to have “difficulties in reading, writing, spelling and organization” and it is of neurobiological origin, meaning that there is involvement of the brain in this disorder (Dyslexia International, 2014; Lyon, S. Shaywitz, and B. Shaywitz, 2003, p. 2).However, this does not mean there is a lack of knowledge within dyslexics. Data states that about every 1 in 10 people are dyslexic (Dyslexia International, 2014); this means that about 70 million people in the world are affected by this learning disability and some of these people die without being diagnosed. Looking into the origin of this disorder could help us develop drugs to help those with the worst cases of this disorder. In addition, things like the ability to screen children to see if they are at risk could rise from this discovery.
Research has been conducted to prove dyslexia’s heritability and neurobiological origin (Lyon et al., 2003; Scerri & Schulte-Korne, 2009; Svensson et al., 2010). Due to this discovery, current research has been focusing on the potential genes, or dyslexia gene candidates, involved with dyslexia (Bates et al., 2009; Cope et al., 2005; Marino et al., 2010; Scerri et al., 2011; Svensson et al., 2010; Venkatesh et al., 2013; Wilke et al., 2009). Dyslexia’s neurobiological origin is very complex and is slowly being revealed. However, it seems like the focus of current research is on the candidate genes and not much is being done outside of those parameters.
I would like to observe outside of those parameters and look at a different aspect of dyslexia. If we just concentrate all our time one one area of the disorder, we may uncover valuable information behind it, but all aspects of dyslexia must be examined in order to understand the disorder in full. In all my research conducted I found a multitude of research that revolved around the dyslexia candidate genes and little research around the gender association of the disorder. The information I uncovered displayed that dyslexia effects a female more severally than a male, but no explanation for why this was, was stated (Sandu et al., 2008). This research could be taken even further by determining why dyslexia affects a female more severely.
This research study will examine the neurobiological differences within a male and female dyslexic. Looking at images of the brains in both genders and comparing them has already been done (Sandu et al., 2008). So the next step is to examine further into the brain and determine why these differences are present. I propose that this can be done through genetic imaging of the differing brains. Understanding the differences between a dyslexic female brain and male brain will hopefully lead to genetic correlations with candidate genes or uncover a new candidate gene. Looking at a different aspect of dyslexia will hopefully help fully uncover the origin of the disorder.
In the literature review we will look at past studies related to the genetics of dyslexia. It all begins with the realization that genes have a relationship with dyslexia, which was done through research of generations of the same family. This research was done due to the frequent reports of educators stating that dyslexics had a strong positive family history (Smith, Kinberling, Pennington, & Lubs, 1983). After that, research moved towards analysis of the genes that were found to be possibly related to dyslexia. This is currently the most important aspect of research due to dyslexia’s connection with genetics, but other topics related to dyslexia, like gender association and comorbidity, are also being studied. Dyslexia has a very complex origin that is slowly being revealed. Although, research in areas outside of just genes themselves needs to be done to fully understand the neurobiological origin of dyslexia within a human.
Currently the main focus on dyslexic research revolves around candidate genes of dyslexia. Candidate genes of dyslexia are the identified genes, through a fair amount of research, that may possibly be associated with dyslexia and how it affects a person genetically. As of 2010 there are six candidate genes related to dyslexia: KIAA0319, DYX1C1, DCDC2, ROBO1, MRPL19 and C2ORF3 (Svensson et al.). A few of the major dyslexic candidate genes are KIAA0319, DCDC2, and DYX1C1.
KIAA0319 is a candidate gene that lies on chromosome 6 (Cope et al., 2005). According to Cope et al. (2005), the research they conducted displayed strong evidence of KIAA0319’s association with dyslexia. Their data matches up with data from previous studies; therefore, the evidence is matching up. In addition, Scerri et al. (2011) provided further support of KIAA0319’s association with reading skills. Then KIAA0319 became a little more interesting; in 2013 a study was conducted on in Indian population. It determined that KIAA0319 was expressed in different parts of the brain and also that it has a role in neuronal migration and the “development of the neocortex” (Venkatesh et al., 2013, p. 534). Its association of neuronal migration, gives strong evidence to its association with dyslexia because it has to do with how the neurons develop within a human, mainly a human’s brain. If dysfunction within neuronal migration occurs, the brain affected is underdeveloped, like those with learning disabilities like dyslexia. Therefore, KIAA0319 has a long line of evidence that justifies its title of a candidate gene for dyslexia.
DCDC2 is another candidate gene being researched frequently. It has been researched with relation to primary cilium, but other research has been done as well to corroborate its association to dyslexia. In a study performed by Wilke et al. (2009), DCDC2 was looked at in 72 German dyslexics and the results display that DCDC2 played a role within the dyslexics. This also increases the thought of damaged neuronal migration as a possible cause of dyslexia. Recent research also finds evidence of DCDC2’s association with mathematics (Marino et al., 2010). There seems to be a pleiotropic effect of DCDC2 within addition and subtraction of one digit numbers, and multiplication of “nuclear families of developmental dyslexia” (Marino et al., 2010, p. 67). DCDC2 has evolving evidence that strongly suggests that it is in some way associated with dyslexia.
DYX1C1 is also considered a candidate gene for dyslexia (Svensson et al., 2010). One of its earliest appearances was in 1983 in the study done by Smith, Kimberling, Pennington, and Lubs. This research was done through linkage analysis of families. The authors determined that there were probably many different etiologies to dyslexia, but due to the fact that many families being affected by it, they concluded that the primary effect may be of genetic origin (Smith et al., 1983). So they analyzed the linkage of families and found that a gene that was significantly involved resided on chromosome 15. Eventually researches found that one particular area of chromosome 15 seemed to be the area of association with dyslexia, DYX1C1. The research continued on into present day determining that DYX1C1 was associated with reading and spelling ability and it also has effects on short term memory (Bates et al., 2009). Once looking into a study performed in 2010 I found that DYX1C1 was finally considered a candidate gene for dyslexia. The research done to consider a genes association to dyslexia is extensive. It took DYX1C1 27 years before it was finally named a candidate gene for dyslexia and even this title doesn’t necessarily mean that it has a definite role in dyslexia’s origin. It just means that there is a high probability that these candidate genes are associated to dyslexia in some way. Although, this isn’t the only thing researched related to dyslexia.
One particular area I found a bit of research on is the gender association of dyslexia. It is widely known that the gender ratio of reading disabilities has recently been uncovered by Hawke et al. (2009) and their discoveries state that reading difficulties is typically higher in males than females. But if you’re looking at the severity of the reading disability that we are discussing, dyslexia, Sandu et al. (2008) uncover that females are more severely impacted with the disorder than males. The gray and white matter of dyslexic boys and girls were compared to those of the control or normal boys and girls (Sandu et al., 2008). The largest significance was shown between the normal girls and the dyslexic girls. The white matter volume of dyslexic girls was significantly lower than that of non-dyslexic girls (Sandu et al., 2008). Therefore, dyslexia’s impact on females is more severe than its impact on males (Sandu et al., 2008). Although, an issue that emerges from this research is the inability to say or show why females are more severely affected by dyslexia than males and this is where my research proposal comes into action.
I propose a study that will hopefully determine what gene(s) is/are causing female dyslexics to have more severe affects. It will look at different areas of the brain to determine the areas that are more severely affected. Then, those areas of the brain will be analyzed genetically within a non-dyslexic and dyslexic child and a dyslexic female versus a dyslexic male to determine the genetic differences that are occurring. The unveiling of the gene(s) that are labeled to be unordinary or irregular will give researchers either an increase in association of an already existing candidate gene or create a new candidate gene that has a big association to dyslexia.
This research will help the world understand the reasoning’s behind why a female is more severally affected by dyslexia than a male. I will be examining the brains of dyslexic females and males to determine what is causing more severity within female dyslexics. The majority of my methodology will be based upon a prior gender association study conducted in 2008 and it will be developed to include more advanced technology, genetic imaging, that has just recently been introduced into the genetic research of dyslexia (Sandu et al., Wilcke et al., 2012). The method section of each prior studies will be combined to create a method that will answer the question of why female dyslexics are more severely affected by dyslexia.
A study of 120 subjects will be conducted and these subjects will include 30 Caucasian dyslexic females, 30 Caucasian non-dyslexic females, 30 Caucasian dyslexic males, and 30 Caucasian non-dyslexic males. The non-dyslexic males and females will be used as the control group for the experiment. This specific study will focus on just Caucasians in order to try to eliminate other factors, like ethnicity, that could cause a differentiation in the brain images and activity. The ages of these test subjects will range from 12 to 14 years old. All test subjects will be chosen based upon consent of themselves and their parents, an assessment done by a psychiatrist and multiple different tests on cognition skills, literacy achievement and reading processing. This process of selecting candidates was developed from Sandu et al.’s (2008) prior study. A failure of 2 or more phonological test along with a history of reading issues will result in the child being identified as dyslexic. If there is no history of reading problems, the child must fail at least 3 phonological tests as well as at least 2 literacy tests to be considered dyslexic. The process for deciding whether or not a child would be considered dyslexic was derived from a prior study, Svensson et al. (2010).
The genetic imaging being done on the brain will be done through fMRIs and genetic association. fMRIs allow medical professionals the capability of looking at what areas of the brain are in control of different functions of a human. The fMRI differs from an MRI due to its ability to detect blood flow. When an area of your brain becomes active, the neurons which cause the increase in activity, require more oxygen. Since oxygen is transported via red blood cells, the area of the brain that is detected by the fMRI is the area you are using for the task you are performing. The genetic variants in the areas specific to phonological and cognitive skills will be observed to determine the genes involved in those skills. In addition, the brain will be split into 8 different areas (Appendix A). Each area of the brain will be examined separately to see the phonological and cognitive functional differences. Increasing the areas split within the brain from the prior gender association study will result in a more thorough observation of the brain (Sandu et al., 2008).
Each child will go through two fMRI scans that employ the same tests. The tests will incorporate 3 different things that incorporate into 5 tests. One test will be related to word decoding abilities, two will be phonologically related and the last two will be on cognitive abilities. These tests will be running during the fMRI scan so that each task or test that is given will show us the area of the brain that functions in order for the task to be completed. The areas of the brain that function during each task will be looked into in more depth. The brain images will help compare the differences in brain functioning for each task and a genetic analysis of each area.
The potential outcome of this study would be an increase in knowledge of candidate gene(s) association with dyslexia, as well as determining what area of the brain is more severely impacted in dyslexic females and what is causing the severity. The increase in knowledge of the areas of the brain that are more severely affected can lead to determining what phonological or cognitive abilities are more severely effect in a female dyslexic. Also, the possible discovery of the same candidate genes having involvement in any area increases its probability of actual being a gene that causes dyslexia. This study will increase our knowledge of the area in the brain of females that are more critically affected than male dyslexics. However, there are some factors that aren’t accounted for in this study.
The study takes into consideration that ethnicity could possibly have a role with dyslexia. This is done by performing this study on only Caucasians. Also, all of the children are within the age range of 12 to 14, so the ages are within a small range. This is done so that the brain development within the children are about the same. However, the age range of the subjects could also be considered too big. All children develop differently at a different pace depending on a multitude of things. Therefore, the capability of the children to do each task can vary due to this factor versus the fact that some children are dyslexic. This is mainly due to the standardized testing that is involved in this research. The requirement of standardized testing will cause a variation in results, but this variation has the capability of being due to the differing development that has been accomplished in each child rather than the dyslexic difference in each child. There are also a few other limitations to this study. First of all, the amount of things like tests that are required result in a very costly study, especially since the size sample is large, with 120 children. Another limitation is that is study is only focused on Caucasians; it gives answers to only a portion of the people affected by dyslexia. In addition to those limitations we have the possibility of inaccurate data portrayed by the fMRI. There could be another factor that causes increased blood flow in an area of the brain that would cause the fMRI to pick it up as the site of activation for the task, although it may not be.
The increase in knowledge of the areas of the brain that are more severely effect by dyslexia in a female would add to Sandu et al. (2008) study by giving a reason for why dyslexia affects females more severely than males. In addition, the possibility of uncovering a gene or genes that causes this severity would give rise to a candidate gene that has been seen within the brains of dyslexics that actually plays a role in dyslexia’s affects. It would solidify a gene’s role in dyslexia. Of course more studies on the gene must be conducted to make certain that the specific gene plays an actual role in dyslexia, but this study will establish gender association as an area worthy of exploring in studying dyslexia.
With the information gained from this study further research can be conducted on the genes that are found to have an association with the severity of dyslexia. Further research on the genes will hopefully lead to finally uncovering at least part of the gene(s) associated to the neurobiological origin of dyslexia.
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