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| Another area of family studies is sibling pair heritability, as in Rabin's study (Rabin et al., 1993) of nine families with three generation of RD. Originally, these families were determined from previous QTL Chromosome 15 sample groups of linkage analyses. In this study, Rabin found that Chromosome 1 was a possible QTL through protein markers with supportive evidence from Froster's study (Froster et al., 1993) mentioned below. The problems with this study were taking sample groups based on previous linkage studies instead of random sampling. Yet, this study was the first to directly mention an attempt to map the QTL to Chromosome 1 through markers. Another study done was a genealogical pedigree for one German family with the RD criteria partially based on the family�s self-assessment for dyslexia. The results suggested a QTL on Chromosomes 1 and 2 as a mutation through translocation. The problems with this study were the limited sample size, preliminary criteria including self-assessment without prior testing, and this paper�s focus on Chromosome 6 and 15. Finally, the problem of being a study from Germany could incorporate cultural bias in defining dyslexia and that heritability may differ for each population and each environment. "In humans, however, it is very difficult to determine whether a particular trait is heritable." (Griffiths et al., 1996) Linkage/heterogeneity Studies This paper's main focus was on Chromosome 6 and 15 due to the limited scope of evidence for inheriting RDs. Some of these studies, Rabin and Froster, were mentioned in the above Family section. Some of the linkage analysis studies seeking a single-gene hypothesized that RDs are autosomal dominant as research begun by Hallgren in the 1950s (DeFries et al., 1991). Later, this study was revisited by Finucci in 1976 and Stevenson in 1987. Both these studies found that RD have more than one mode of transmission that depends on the family. For instance, Finucci found that these possible modes of transmission were either autosomal dominant, autosomal recessive, or multifactoral inheritance based on the complexities associated with defining SLDs and determining human heredity for behavioral traits. Stevenson also found that the inheritance of RDs was either autosomal dominant or a QTL on Chromosome 15. The problem with these studies was the use of Hallgren�s data set from the 1950s when SLD was an unknown behavioral trait and the limited sample sizes. This limited sample size was problematic in Stevenson�s study due to only one of nine families showed the QTL on Chromosome 15 and the other families did not all demonstrate autosomal dominant inheritance. Pennington also studied autosomal dominance which was verified for only 20% of the families. These studies of autosomal dominance started a debate on penetrance, especially for females. The debate was whether RDs were fully or partially penetrant but no study has shown that dyslexia is sex-linked. This lack of sex-linked data suggests that RDs are not a simple Mendelian trait and that the phenotypic variance of more males with RDs is probably a bias on the subjective diagnosis for SLD assessment. A final note on Finucci's study was this research began further hypothesis on the possible heterogeneity of RDs and seeking QTLs on Chromosomes 1,6, and 15. This paper focused on Chromosomes 6 (C6) and 15 (C15) due to more research with less complexity as mentioned in the introduction. As previously mentioned, Stevenson found C15 as a QTL for one family. Another study like Finucci�s was done in Denmark by Bisgaard with the first hypothesis being to study the heterogeneity of RDs through C15. The null hypothesis was accepted which led to the next hypothesis of homogeneity in RDs. yet, there were problems with this study having a cultural bias like Froster's study mentioned in the above section. Another problem with suggesting RDs being homogenous was if that meant to the RD population only or if this study was meant to represent the entire population; thus, another debate on which populations these studies were representing. Another C15 QTL study was done by Smith et al. that also considered C6. Again, this research showed only one family with C15 heritability while some of the other families showed C6 heritability. This study also had limited sample sizes and represented the complexities of human heredity especially in a controversially defined disorder such as dyslexia. |
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