A molecular genetic study of autism and related phenotypes in extended pedigrees

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Piven, Joseph
    • Affiliation: School of Medicine, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Vieland, Veronica J.
    • Other Affiliation: Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital
  • Parlier, Morgan
    • Affiliation: School of Medicine, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Thompson, Ann
    • Other Affiliation: McMaster Department of Psychiatry and Behavioural Neurosciences
  • O’Conner, Irene
    • Other Affiliation: McMaster Department of Psychiatry and Behavioural Neurosciences
  • Woodbury-Smith, Mark
    • Other Affiliation: McMaster Department of Psychiatry and Behavioural Neurosciences
  • Huang, Yungui
    • Other Affiliation: Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital
  • Walters, Kimberly A.
    • Other Affiliation: Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital
  • Fernandez, Bridget
    • Other Affiliation: Provincial Medical Genetics Program, Health Sciences Center
  • Szatmari, Peter
    • Other Affiliation: McMaster Department of Psychiatry and Behavioural Neurosciences
Abstract
  • Background: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas ‘repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD.
Date of publication
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Joseph Piven et al.; licensee BioMed Central Ltd.
License
Journal title
  • Journal of Neurodevelopmental Disorders
Journal volume
  • 5
Journal issue
  • 1
Page start
  • 30
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1866-1955
Bibliographic citation
  • Journal of Neurodevelopmental Disorders. 2013 Oct 05;5(1):30
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • October 10, 2013

Relations

Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
file details 1866-1955-5-30.pdf 2019-05-07 Public Download
file details 1866-1955-5-30.xml 2019-05-07 Public Download