A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States.
Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb region spanning the gene TTRAP and the first four exons of the neighboring uncharacterized gene KIAA0319. The region of association is also directly upstream of a third gene, THEM2. We found evidence of these associations in a second sample of siblings from the United Kingdom, as well as in an independent sample of twin-based sibships from Colorado. One main RD risk haplotype that has a frequency of approximately 12% was found in both the U.K. and U.S. samples. The haplotype is not distinguished by any protein-coding polymorphisms, and, therefore, the functional variation may relate to gene expression. The QTL influences a broad range of reading-related cognitive abilities but has no significant impact on general cognitive performance in these samples. In addition, the QTL effect may be largely limited to the severe range of reading disability.
Francks
Clyde
C
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Paracchini
Silvia
S
Smith
Shelley D
SD
Richardson
Alex J
AJ
Scerri
Tom S
TS
Cardon
Lon R
LR
Marlow
Angela J
AJ
MacPhie
I Laurence
IL
Walter
Janet
J
Pennington
Bruce F
BF
Fisher
Simon E
SE
Olson
Richard K
RK
DeFries
John C
JC
Stein
John F
JF
Monaco
Anthony P
AP
D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003120:Colorado; D004410:Dyslexia / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D035781:Siblings; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics; D006113:United Kingdom
D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins