Download Running Head: THE GENDER ASSOCIATION OF DYSLEXIA THE

Running Head: THE GENDER ASSOCIATION OF DYSLEXIA
The Gender Association of Dyslexia
Student Sample
Wayne State University
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THE GENDER ASSOCIATION OF DYSLEXIA
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Abstract
In this paper I am proposing a study on the gender association in relation to
dyslexia. The association is genetic, meaning that it deals with the heredity and genetics
of dyslexia. Dyslexia is a highly inheritable learning disability that is of neurobiological
origin, but the origin is unclear (Lyon, S. Shaywitz, and B. Shaywitz, 2003, p. 2). It has
been researched throughout many years and continues to be researched today. A lot of
current research is dedicated to dyslexia candidate genes, which are genes that could
possibly have an association with dyslexia. My research proposal strays away from this
research, I am proposing a gender association view on dyslexia. In all my research I
found one gender association study and the majority of the other studies were some
how related to dyslexia candidate genes. I would like to expand the research field of the
genetics behind dyslexia. It was found that female dyslexics are more severely affected
by dyslexia than males in 2008, but no reason for why this is occurring (Sandu et al.,
2008). So, I propose a study that will use fMRIs and genetic analysis to determine why
dyslexia is more severe within females. The outcome of this study could result in an
increase in knowledge of the neurobiological origin of dyslexia.
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Introduction
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
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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.
Literature Review
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
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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.
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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
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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
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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.
Methodology
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
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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).
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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.
Discussion
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,
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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
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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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References
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(2010). Dyslexia and DYX1C1L deficits in reading and spelling associated with a
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Appendix A
The figure below displays the splits in the brain that will occur while examining each
child. There will be a total of 8 different areas that will be examined.