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. 2008 Sep;38(5):462-75.
doi: 10.1007/s10519-008-9215-2. Epub 2008 Jul 8.

Genome scan of a nonword repetition phenotype in families with dyslexia: evidence for multiple loci

Zoran Brkanac  1 , Nicola H Chapman, Robert P Igo Jr, Mark M Matsushita, Kathleen Nielsen, Virginia W Berninger, Ellen M Wijsman, Wendy H Raskind
Affiliations

Genome scan of a nonword repetition phenotype in families with dyslexia: evidence for multiple loci

Zoran Brkanac et al. Behav Genet. 2008 Sep.

Abstract

To understand the genetic architecture of dyslexia and identify the locations of genes involved, we performed linkage analyses in multigenerational families using a phonological memory phenotype--Nonword Repetition (NWR). A genome scan was first performed on 438 people from 51 families (DS-1) and linkage was assessed using variance components (VC), Bayesian oligogenic (BO), and parametric analyses. For replication, the genome scan and analyses were repeated on 693 people from 93 families (DS-2). For the combined set (DS-C), analyses were performed with all three methods in the regions that were identified in both samples. In DS-1, regions on chromosomes 4p, 6q, 12p, 17q, and 22q exceeded our initial threshold for linkage, with 17q providing a parametric LOD score of 3.2. Analysis with DS-2 confirmed the locations on chromosomes 4p and 12p. The strongest VC and BO signals in both samples were on chromosome 4p in DS-C, with a parametric multipoint LOD(max) of 2.36 for the 4p locus. Our linkage analyses of NWR in dyslexia provide suggestive and reproducible evidence for linkage to 4p12 and 12p in both samples, and significant evidence for linkage to 17q in one of the samples. These results warrant further studies of phonological memory and chromosomal regions identified here in other datasets.

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Figures

Fig. 1
Fig. 1
DS-1 whole genome scan for nonword repetition using variance component linkage and Bayesian oligogenic MCMC joint segregation and linkage analysis. The dotted lines mark the thresholds for regions of interest for further analysis
Fig. 2
Fig. 2
DS-2 whole genome scan for nonword repetition using variance component linkage and Bayesian oligogenic MCMC joint segregation and linkage analysis. The dotted lines mark the thresholds for regions of interest for further analysis
Fig. 3
Fig. 3
Multipoint variance component linkage, Bayesian oligogenic MCMC segregation and linkage and parametric linkage analysis for chromosomes 4 and 12 for DS-1, DS-2, and DS-C
See this image and copyright information in PMC

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