Rehabilitation Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Genes Brain Behav. 2023 Dec;22(6):e12859. doi: 10.1111/gbb.12859. Epub 2023 Aug 8.
Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder of unknown etiology that affects one in 20 children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of quantitative trait loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to better understand the human presentation of DCD. Results of this current study confirm differences in motor learning in selected BXD strains and strains with altered cerebellar volume. Five strains - BXD15, BXD27, BXD28, BXD75, and BXD86 - exhibited the most DCD-like phenotype when compared with other BXD strains of interest. Results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD86 strains struggled with both fine and gross motor skills. The functional roles of genes within significant QTLs were assessed in relation to DCD-like behavior. Only Rab3a (Ras-related protein Rab-3A) emerged as a high likelihood candidate gene for the horizontal ladder rung task. This gene is associated with brain and skeletal muscle development, but lacked nonsynonymous polymorphisms. This study along with Gill et al. (same issue) is the first studies to specifically examine the genetic linkage of DCD using BXD strains of mice.
发育性协调障碍（DCD）是一种病因不明的神经发育障碍，影响每 20 名儿童中的 1 名。有迹象表明，DCD 具有潜在的遗传成分，因为它的遗传性很高。因此，我们探索使用一种称为 BXD 面板的重组近交系小鼠来了解复杂特征（即运动学习）的遗传基础，通过识别数量性状基因座（QTL）。本研究的总体目标是利用 QTL 方法评估 BXD 系小鼠的基因组-表型相关性，以更好地理解 DCD 的人类表现。本研究的结果证实了选定 BXD 系和小脑体积改变的系之间运动学习的差异。与其他 BXD 系相比，5 个系 - BXD15、BXD27、BXD28、BXD75 和 BXD86 - 表现出最类似于 DCD 的表型。结果表明，BXD15 和 BXD75 主要在粗大运动技能方面存在困难，BXD28 主要在精细运动技能方面存在困难，BXD27 和 BXD86 系在精细和粗大运动技能方面均存在困难。在与 DCD 样行为相关的情况下，评估了显著 QTL 内基因的功能作用。只有 Rab3a（Ras 相关蛋白 Rab-3A）作为水平梯级任务的高可能性候选基因出现。该基因与脑和骨骼肌发育有关，但缺乏非同义多态性。这项研究与 Gill 等人（同一期）一起，是首次使用 BXD 系小鼠专门研究 DCD 的遗传连锁。
