## 4 Discussion
Based on these tenets and on the experimental work reporting a link between the cerebral levels of glutamate and reading abilities, we wondered whether the proteins described as markers of dyslexia could be proteins enriched in glutamate and thus particularly dependent on oxygenation for their expression. In particular, the investigation of several cerebral areas has demonstrated that high values of glutamate have a positive correlation with reading ability in 6 to 10-year-old children, while glutamine has a negative correlation with language skills [11]. Indeed, the median value of Glu in proteins markers of dyslexia is higher than the value calculated for all proteins codified by the human genome: 49 vs. 27 respectively, as absolute content, and 0.08 vs. 0.06, as relative frequencies (% of the total). In our previous work, we also found some evidence suggesting that gene clustering may represent an adaptation for responding to amino acid availability [8]. Again, we hypothesized that dyslexia loci could be regions of chromosome codifying for proteins enriched in glutamate, therefore, sensitive to oxygenation for their translation. To test our hypothesis, we performed a proof of concept investigation; we used our novel procedure to analyze the content of Glu of proteins codified by chromosome 15, which encompasses a locus for dyslexia. We obtained a list of proteins ordered by their translation position on the chromosome, and by chromosome walking and surfing analysis, we were able to find the regions of the chromosome codifying for proteins most enriched in Glu. By this analysis, we found the confirmation that the dyslexia locus DYXI overlapswith a length of DNA producing proteins with more glutamate than what codified by the neighboring genes. We concluded that the DYX1 is a gene cluster whose expression could be limited by environmental conditions and AA availability. For example, it is reasonable to expect that the proteins of the locus will be scarcely expressed in a hypoxic environment, thus revealing an interesting link between hypoxia and dyslexia. Most intriguing, our analysis discovered other three regions whose proteins are enriched in Glu; these regions could be potential loci of dyslexia, yet to be explored. We believe that this novel method of matching databases and analyzing AA content could be applied to many other disorders linked to hypoxia and to many AA other than Glu. The linkage to a region of chromosome 15 has also been demonstrated for autism (reviewed in [25]). Interestingly, several studies assessing the levels of amino acids in the brain and serum of patients with autism spectrum disorder (ASD) have reported increased levels of glutamine, or the sum of glutamate and glutamine, in specific brain regions of ASD patients, in association with lower intelligence quotient and greater impairments in social cognition, compared to typically developing individuals [26; 27]. Moreover, recent studies have described a reduction of essential amino acid levels and sex-specific alterations in serum amino acid concentration profiles in children with autism spectrum disorder, and an increasing number of studies indicate that patients with ASD may have unique metabolic patterns with a variety of amino acid metabolism dysregulations [28; 29]. Based on these observations, the analysis of chromosomes, focusing particularly on chromosome 15, could exploit the chromosome walking approach to discover differences in the amino acid composition of proteins codified by the reported ASD loci [30; 31; 32] and could reveal further critical regions. Although there are many influencing factors, the base composition is considered as the driving force in amino acid usage. In fact, the variability of the amino acidic composition of human proteins has been found strongly correlated with the GC content of first and second codon positions and the GC level of the corresponding flanking regions.