Developmental coordination disorder: What can we learn from RI mice using motor learning tasks and QTL analysis

Author:

Gill Kamaldeep12ORCID,Rajan Jeffy Rajan Soundara34,Chow Eric24,Ashbrook David G.5ORCID,Williams Robert W.5,Zwicker Jill G.267ORCID,Goldowitz Daniel234ORCID

Affiliation:

1. Rehabilitation Sciences, University of British Columbia Vancouver British Columbia Canada

2. British Columbia Children's Hospital Research Institute Vancouver British Columbia Canada

3. Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada

4. Centre for Molecular Medicine and Therapeutics Department of Medical Genetics, University of British Columbia Vancouver British Columbia Canada

5. Department of Genetics Genomics and Informatics, University of Tennessee Health Science Center Memphis Tennessee USA

6. Department of Occupational Science & Occupational Therapy University of British Columbia Vancouver British Columbia Canada

7. Department of Pediatrics University of British Columbia Vancouver British Columbia Canada

Abstract

AbstractDevelopmental 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.

Funder

BC Children's Hospital Research Institute

Canadian Institutes of Health Research

Publisher

Wiley

Subject

Behavioral Neuroscience,Neurology,Genetics

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