The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia.
The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia.
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DOI：
10.1371/journal.pgen.0010050
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发表时间：
2005-10
期刊：
影响因子：
4.5
通讯作者：
Kere J
中科院分区：
文献类型：
--
作者：
Hannula-Jouppi K;Kaminen-Ahola N;Taipale M;Eklund R;Nopola-Hemmi J;Kääriäinen H;Kere J
诵读困难，或特定的阅读障碍，是最常见的学习障碍，具有复杂的部分遗传基础，但其生化机制仍然知之甚少。3号染色体上的DYX 5基因座与一个大家族中的阅读障碍和一个小家族中的语音障碍有关。我们发现，轴突导向受体基因ROBO 1，orthopathic到果蝇roundabout基因，被破坏的染色体易位在一个睡眠障碍的个人。在一个大的家系中，21个阅读障碍个体与ROBO 1的特定单倍型遗传连锁（在我们的样本中没有发现任何其他染色体），ROBO 1从这个单倍型的表达在受影响的个体中不存在或减弱。类人猿ROBO 1基因的测序揭示了多个编码差异，与猩猩相比，人类、黑猩猩和大猩猩分支之间的选择压力显著不同。我们还发现了ROBO 1的新外显子和剪接变体，这可能解释了人类和小鼠在ROBO 1杂合缺失中的表型差异。我们的结论是，阅读障碍可能是由于部分单倍不足的ROBO 1在罕见的家庭。因此，我们的数据表明，穿过大脑半球之间中线的神经元轴突、树突引导或ROBO 1的另一种功能的轻微干扰可能表现为人类的特定阅读障碍。诵读困难，或特定的阅读障碍，是一种常见的学习障碍，具有复杂的部分遗传基础。已经确定了许多含有与阅读障碍有关的基因的染色体区域，在这项研究中，作者描述了3号染色体上一个名为DYX 5的候选基因。作者表明，轴突导向受体基因ROBO 1在一个阅读障碍个体中被染色体易位破坏;此外，这项研究表明，在一个阅读障碍与DYX 5有关的大型谱系中，阅读障碍患者的染色体上ROBO 1的表达减少。ROBO 1在调节轴突穿过大脑半球之间的中线和引导神经元树突方面具有作用。这些发现表明，在罕见的家族中，阅读障碍可能是由ROBO 1表达的微小变化引起的，例如一个功能拷贝的丢失。因此，ROBO 1是阅读障碍易感基因的候选者。
Dyslexia, or specific reading disability, is the most common learning disorder with a complex, partially genetic basis, but its biochemical mechanisms remain poorly understood. A locus on Chromosome 3, DYX5, has been linked to dyslexia in one large family and speech-sound disorder in a subset of small families. We found that the axon guidance receptor gene ROBO1, orthologous to the Drosophila roundabout gene, is disrupted by a chromosome translocation in a dyslexic individual. In a large pedigree with 21 dyslexic individuals genetically linked to a specific haplotype of ROBO1 (not found in any other chromosomes in our samples), the expression of ROBO1 from this haplotype was absent or attenuated in affected individuals. Sequencing of ROBO1 in apes revealed multiple coding differences, and the selection pressure was significantly different between the human, chimpanzee, and gorilla branch as compared to orangutan. We also identified novel exons and splice variants of ROBO1 that may explain the apparent phenotypic differences between human and mouse in heterozygous loss of ROBO1. We conclude that dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans. Dyslexia, or specific reading disability, is a common learning disorder with a complex, partially genetic basis. A number of chromosomal regions harboring genes involved in dyslexia have been identified, and in this study the authors describe a candidate gene from one such locus, called DYX5, on Chromosome 3. The authors show that an axon guidance receptor gene, ROBO1, is disrupted by a chromosomal translocation in one dyslexic individual; furthermore, this study shows that the expression of ROBO1 is reduced on chromosomes from dyslexics in a large pedigree in which dyslexia has been linked to DYX5. ROBO1 has a role in regulating axon crossing across the midline between brain hemispheres and guidance of neuronal dendrites. As suggested by these findings, dyslexia may be caused in rare families by a small change in the expression of ROBO1, such as loss of one functional copy. Thus, ROBO1 is a candidate for a dyslexia susceptibility gene.
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DOI：
10.1002/ajmg.b.30018
发表时间：
2004-11-15
影响因子：
2.8
作者：
Chapman, NH;Igo, RP;Raskind, WH
通讯作者：
Raskind, WH
影响因子：
8
作者：
Dallol, A;Forgacs, E;Latif, F
通讯作者：
Latif, F
影响因子：
9.8
作者：
Cope, N;Harold, D;Williams, J
通讯作者：
Williams, J
DOI：
10.1016/s0169-328x(99)00329-0
发表时间：
2000-03-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Cammarota, M;Bevilaqua, LRM;Medina, JH
通讯作者：
Medina, JH
影响因子：
64.5
作者：
Bashaw, GJ;Kidd, T;Goodman, CS
通讯作者：
Goodman, CS