Article

European Journal of Human Genetics (2005) 13, 491–499. doi:10.1038/sj.ejhg.5201356 Published online 26 January 2005

A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia

Cecilia Marino1, Roberto Giorda2, Maria Luisa Lorusso3, Laura Vanzin1, Nello Salandi1, Maria Nobile1, Alessandra Citterio1, Silvana Beri2, Valentina Crespi1, Marco Battaglia4,5 and Massimo Molteni1

  1. 1Department of Child Psychiatry, Scientific Institute 'Eugenio Medea', via Don L Monza 20, 23842 Bosisio Parini (LC), Italy
  2. 2Molecular Biology Laboratory, Scientific Institute 'Eugenio Medea', via Don L Monza 20, 23842 Bosisio Parini (LC), Italy
  3. 3Department of Neuropsychology, Scientific Institute 'Eugenio Medea', via Don L Monza 20, 23842 Bosisio Parini (LC), Italy
  4. 4Department of Psychology, Vita-Salute San Raffaele University at IRCCS 'San Raffaele', via Stamira d'Ancona 20, Milan, Italy
  5. 5Division of Epidemiology, National Institutes of Public Health, P.O. Box 4404 Nydalen, Oslo, Norway

Correspondence: Dr C Marino, Department of Child Psychiatry, Scientific Institute 'Eugenio Medea', via Don L Monza 20, 23842 Bosisio Parini (LC), Italy. Tel: +39 031 877 595; Fax: +39 031 877 356; E-mail: cmarino@bp.lnf.it

Received 17 July 2004; Revised 8 November 2004; Accepted 11 November 2004; Published online 26 January 2005.

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Abstract

We applied a family-based association approach to investigate the role of the DYX1C1 gene on chromosome 15q as a candidate gene for developmental dyslexia (DD) to 158 families containing at least one dyslexic child. We directly sequenced exons 2 and 10 of the DYX1C1 gene and found eight single nucleotide polymorphism (SNPs), three of which (-3G>A, 1249 G>T, 1259 C>G) were suitable for the genetic analyses. We performed single- and multimarker association analyses with DD as a categorical trait by FBAT version 1.4 and TRANSMIT version 2.5.4 programs. Our sample had a power of at least 80% to detect an association between the selected phenotypes and the informative polymorphisms at a significance level of 5%. The results of the categorical analyses did not support the involvement of the DYX1C1 gene variants in this sample of dyslexics and their relatives. Quantitative and multimarker analyses, which provide greater power to detect loci with a minor effect, consistently yielded nonsignificant results. While D1X1C1 is a good candidate gene for DD, we were unable to replicate the original findings between DYX1C1 gene and DD, perhaps due to genetic heterogeneity.

Keywords:

developmental dyslexia, DYX1C1, quantitative analysis, family-based association study

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