Couto Jillian M, Gomez Lissette, Wigg Karen, Cate-Carter Tasha, Archibald Jennifer, Anderson Barbara, Tannock Rosemary, Kerr Elizabeth N, Lovett Maureen W, Humphries Tom, Barr Cathy L
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
J Neurogenet. 2008;22(4):295-313. doi: 10.1080/01677060802354328.
A locus on chromosome 1p34-36 (DYX8) has been linked to developmental dyslexia or reading disabilities (RD) in three independent samples. In the current study, we investigated a candidate gene KIAA0319-Like (KIAA0319L) within DYX8, as it is homologous to KIAA0319, a strong RD candidate gene on chromosome 6p (DYX2). Association was assessed by using five tagging single nucleotide polymorphisms in a sample of 291 nuclear families ascertained through a proband with reading difficulties. Evidence of association was found for a single marker (rs7523017; P=0.042) and a haplotype (P=0.031), with RD defined as a categorical trait in a subset of the sample (n=156 families) with a proband that made our criteria for RD. The same haplotype also showed evidence for association with quantitative measures of word-reading efficiency (i.e., a composite score of word identification and decoding; P=0.032) and rapid naming of objects and colors (P=0.047) when analyzed using the entire sample. Although the results from the current study are modestly significant and would not withstand a correction for multiple testing, KIAA0319L remains an intriguing positional and functional candidate for RD, especially when considered alongside the supporting evidence for its homolog KIAA0319 on chromosome 6p. Additional studies in independent samples are now required to confirm these findings.
1号染色体p34 - 36区域（DYX8）上的一个基因座已在三个独立样本中与发育性阅读障碍或阅读障碍（RD）相关联。在本研究中，我们调查了DYX8区域内的一个候选基因KIAA0319样基因（KIAA0319L），因为它与KIAA0319同源，KIAA0319是6号染色体p区域（DYX2）上一个强有力的阅读障碍候选基因。我们通过在291个核心家庭样本中使用5个标签单核苷酸多态性来评估关联性，这些家庭是通过一名有阅读困难的先证者确定的。在样本的一个子集中（n = 156个家庭），先证者符合我们的阅读障碍标准，将阅读障碍定义为分类性状时，发现一个单一标记（rs7523017；P = 0.042）和一个单倍型（P = 0.031）存在关联证据。使用整个样本进行分析时，相同的单倍型也显示出与单词阅读效率的定量测量（即单词识别和解码的综合得分；P = 0.032）以及物体和颜色的快速命名（P = 0.047）存在关联证据。尽管本研究的结果有一定显著性，但无法经受多重检验校正，KIAA0319L仍然是阅读障碍一个有趣的位置和功能候选基因，特别是当与6号染色体p区域上其同源基因KIAA0319的支持证据一起考虑时。现在需要在独立样本中进行更多研究来证实这些发现。
