Quantitative-Trait Locus for Specific Language and Reading Deficits on Chromosome 6p

Gayán, Javier; Smith, Shelley D.; Cherny, Stacey S.; Cardon, Lon R.; Fulker, David W.; Brower, Amy; Olson, Richard K.; Pennington, Bruce F.; DeFries, John C.

doi:10.1086/302191

Cited by 241 publications

(205 citation statements)

References 27 publications

(30 reference statements)

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“…Phonemic reading may be influenced to a larger extent by QTLs in region 6p than is orthographic coding or whole word reading required for irregular words. While orthographic coding has been shown to be linked to this region (e.g., Gayan et al, 1999), the Cambridge test differs from orthographic coding tests used to assess dyslexia in that it contains low frequency irregular words to tap IQ. Although there was a discrepancy in the linkage findings for our two reading tests on 6p, consistent and larger peaks were shown in a region (7q32-q34) found significant in a Finnish cohort (Kaminen et al, 2003), with the peak LOD score for the Cambridge (1.82) being for the same marker (D7S530) reported in the Finnish study.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

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A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

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Section: Discussionmentioning

confidence: 99%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

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“…[1][2][3][4][5][6][7][8] Linkage studies have identified several genomic regions that may harbor susceptibility quantitative trait loci (QTL) for DD, and the most consistently replicated of these is DYX2, which lies on chromosome 6p22.2. 1,[9][10][11][12][13][14][15][16] A number of association studies have now been performed attempting to identify the DYX2 susceptibility locus. In independent samples from the UK and the US, we previously found evidence that variation in the KIAA0319 gene confers risk of dyslexia.…”

Section: Introductionmentioning

confidence: 99%

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia

et al. 2006

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The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5 0 flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.

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“…[22][23][24] However, studies in the general population show that dyslexia and its component processes are genetically heterogeneous and likely involve the influence of multiple genes. Targeted and genome-wide linkage analyses have reported possible localizations for genes contributing to reading and spelling and a variety of related processes on chromosomes 1p34-36 (DYX8) 25,26 , 2p16-15 (DYX3) 20,[27][28][29] , 3p12-q13 (DYX5) 21 , 6p21.3 (DYX2) [30][31][32][33][34][35] , 6q13-16.2 (DYX4) 36 , 11p15.5 (DYX7) 37 , 15q21 (DYX1) 32,[37][38][39][40][41][42] , and 18p11 (DYX6) 27 .…”

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confidence: 99%

A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency

et al. 2005

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Dyslexia is a common and complex developmental disorder manifested by unexpected difficulty in learning to read. Multiple different measures are used for diagnosis, and may reflect different biological pathways related to the disorder. Impaired phonological decoding (translation of written words without meaning cues into spoken words) is thought to be a core deficit. We present a genome scan of two continuous measures of phonological decoding ability: phonemic decoding efficiency (PDE) and word attack (WA). PDE measures both accuracy and speed of phonological decoding, whereas WA measures accuracy alone. Multipoint variance component linkage analyses (VC) and Markov chain Monte-Carlo (MCMC) multipoint joint linkage and segregation analyses were performed on 108 families. A strong signal was observed on chromosome 2 for PDE using both VC (LOD ¼ 2.65) and MCMC methods (intensity ratio (IR) ¼ 32.1). The IR is an estimate of the ratio of the posterior to prior probability of linkage in MCMC analysis. The chromosome 2 signal was not seen for WA. More detailed mapping with additional markers provided statistically significant evidence for linkage of PDE to chromosome 2, with VC-LOD ¼ 3.0 and IR ¼ 59.6 at D2S1399. Parametric analyses of PDE, using a model obtained by complex segregation analysis, provided a multipoint maximum LOD ¼ 2.89. The consistency of results from three analytic approaches provides strong evidence for a locus on chromosome 2 that influences speed but not accuracy of phonological decoding. Molecular Psychiatry (2005) 10, 699-711.

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Quantitative-Trait Locus for Specific Language and Reading Deficits on Chromosome 6p

Cited by 241 publications

References 27 publications

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia

A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency

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