Scientific Article Review

This web page was produced as an assignment for Genetics 677, an undergraduate course at University of Wisconsin: Madison.

Picture
Figure 1. From scientific article showing the further expansion of a 110-kb region within DCDC2. SNPs
labeled with an asterisk are associated with RD phenotypes with P < 0.005. C_449792 is located within the deleted 2,445 bp in intron 2 of DCDC2 and
designated by a triangle. The heavy vertical black lines represent exons inDCDC2.

Scientific Article

Brief Summary:   
   The authors in the paper, "DCDC2 is associated with reading disability and modulates neuronal development in the brain", wanted to study reading disability (RD) also known as developmental dyslexia. Developmental dyslexia is intriguing to authors since it has prevalence rates between 5% and 17%, and is a common complex neurobehavioral disorder known to affect individuals who have normal intelligence and adequate educational opportunity, but have an impaired reading ability. In addition, the authors knew from prior studies that people who are dyslexic have altered brain patterns compared to fluent readers when challenged with reading tasks, and due to these altered brain patterns the authors believe these studies show where key genes involved in reading and language within specific brain locations are expressed and are changed in RD.

   This knowledge led the authors to investigate a locus known as DYX2 located on chromosome 6 p-arm 22 which is the most widely known, most susceptible, and most replicated region associated with RD. The goal of the authors was to identify the DYX2 gene and its corresponding alleles responsible for susceptibility to RD and to assemble a small number candidate genes to investigate. In order to start this study, the authors collected a sample size of 536 parents and siblings.  People with an IQ below 80 and English as a second language were excluded from the initial sample collected from the Colorado Learning Disabilities Research Center (CLDRC). The authors put together a high-density marker panel of 147 single nucleotide polymorphisms (SNPs) to identify high candidate genes. Through a QTDT (quantitative transmission disequilibrium test) analysis the authors identified 5 SNPs with P-value < .01.  Two of the SNPs were in DCDC2. The authors performed a linkage disequilibrium analysis between the pair of SNPs The authors discovered five haplotype blocks, labeled A-E, that showed linkage disequilibrium within the DCDC2.

   Here are some definitions one may need to knowto clarify the above paragraph. Linkage disequilibrium occurs when blocks of sequences on the same chromosome are inherited together since they lack recombination between or throughout the sequences. Those DNA sequences happen to have alleles grouped together that are rarely separated due to the lack of recombination between them are known as haplotypes within the human genome.

   Out of those five haplotype blocks, the authors discover A, C, D, and E were associated with impaired performance on reading tasks while IQ was preserved. In addition, the authors found that large polymorphic deletion within the intron 2 site of DCDC2 that is responsible for transcription factor (TF) binding sites. Alongside finding this deletion, the authors performed quantitative real time RT-PCR on several genes including DCDC2 to see where each was expressed in the brain. DCDC2 was expressed in the entorhinal cortex, inferior temporal cortex, medial temporal cortex, hypothalamus, amygdala, and hippocampus where fluent reading occurs. Lastly, the authors ran an RNAi experiment on the DCDC2 where they discovered radial neuronal migration is impaired due to down regulation.

   To be perfectly honest, this scientific article was fairly difficult to read and understand. There was a lot of material to wade through, with many experimental protocols and procedures to look over and look up to attempt to understand some of the figures. This article used a lot of acronyms that one would not know without 1) prior knowledge or 2) paying close attention to the article, or 3) googling it. I especially liked the discussion at the end which helped to clear-up and state the importance of their experiment and figures that were presented in the paper. The methods and materials in the middle of the paper created a little confusion during a first read through just to familiarize yourself with the writing style and trying to get an overall picture of what was going on and how they came to their conclusion. The experiments that were performed and set-up seem very well thought out, logical and conclusive. I learned about the process of identifying genes and SNPs from a larger region of DNA genome.

dcdc2_is_associated_with_reading_disability_and_modulates_neuronal_development_in_the_brain.pdf
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References:
Meng, H., S.D. Smith, K. Hager, M. Held, J. Liu, R.K. Olson, B.F. Pennington, et al. (2005). DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proceedings of the National Academy of Sciences of the United States of America 102, 17053-17058.1

Megan Holler
mholler@wisc.edu
Last Updated: 5/13/09