Document Detail

Segregation analysis of phenotypic components of learning disabilities. I. Nonword memory and digit span.
MedLine Citation:
PMID:  10924405     Owner:  NLM     Status:  MEDLINE    
Dyslexia is a common and complex disorder with evidence for a genetic component. Multiple loci (i.e., quantitative-trait loci [QTLs]) are likely to be involved, but the number is unknown. Diagnosis is complicated by the lack of a standard protocol, and many diagnostic measures have been proposed as understanding of the component processes has evolved. One or more genes may, in turn, influence these measures. To date, little work has been done to evaluate the mode of inheritance of individual component-as opposed to composite-phenotypes, beyond family or twin correlation studies that initially demonstrate evidence for a genetic basis of such components. Here we use two approaches to segregation analysis in 102 nuclear families to estimate genetic models for component phenotypes associated with dyslexia: digit span and a nonword-repetition task. Both measures are related to phonological skills, one of the key component processes in dyslexia. We use oligogenic-trait segregation analysis to estimate the number of QTLs contributing to each phenotype, and we use complex segregation analysis to identify the most parsimonious inheritance models. We provide evidence in support of both a major-gene mode of inheritance for the nonword-repetition task, with approximately 2.4 contributing QTLs, and for a genetic basis of digit span, with approximately 1.9 contributing QTLs. Results obtained by reciprocal adjustment of measures suggest that genes contributing to digit span may contribute to the nonword-repetition score but that there are additional QTLs involved in nonword repetition. Our study adds to existing studies of the genetic basis of composite phenotypes related to dyslexia, by providing evidence for major-gene modes of inheritance of these single-measure component phenotypes.
E M Wijsman; D Peterson; A L Leutenegger; J B Thomson; K A Goddard; L Hsu; V W Berninger; W H Raskind
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2000-07-31
Journal Detail:
Title:  American journal of human genetics     Volume:  67     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-09-19     Completed Date:  2000-09-19     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  631-46     Citation Subset:  IM    
Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
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MeSH Terms
Age Factors
Chromosome Segregation / genetics*
Dyslexia / genetics*,  physiopathology*
Fingers / physiology*
Intelligence Tests
Language Tests
Memory / physiology*
Models, Genetic
Multifactorial Inheritance / genetics
Nuclear Family
Quantitative Trait, Heritable
Sex Factors
Statistics as Topic
Grant Support
1 P41 RR03655/RR/NCRR NIH HHS; P50 33812//PHS HHS
Erratum In:
Am J Hum Genet 2000 Sep;67(3):775

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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