Reading disability and chromosome 6p21.3: evaluation of MOG as a candidate gene.
Linkage analysis has localized a gene influencing specific reading disability (dyslexia) to 6p21.3. The myelin oligodendrocyte glycoprotein (MOG) gene, which maps to this region, was selected as a candidate. Myelin oligodendrocyte glycoprotein is a membrane protein, a member of the immunoglobin superfamily, that is found on the outermost lamellae of mature myelin. Although the exact function of this protein is unknown, its presence in the central nervous system and the hypothesized relationship between dyslexia and temporal processing rate as well as a suggested relationship with intelligence made this gene a candidate for dyslexia. Analysis of the coding exons and adjacent splice sites in a subset of 22 children with dyslexia from 10 sibships found a missense mutation in exon 4 in 2 of the sibships. This change from the published sequence also occurred in 86 of 96 random controls, making it considerably less frequent in this small sample of individuals with dyslexia. Subsequent typing of this single nucleotide polymorphism (SNP) in 74 nuclear families in which at least one child had reading disability showed no significant difference in frequency from the controls, however. Sib-pair linkage analysis with these families did not show significant linkage with the SNP nor with a separate polymorphic dinucleotide repeat marker in the MOG gene (MOG31/32), but association analysis identified two alleles of MOG31/32 that were associated with reading disability phenotypes with a low level of significance. Thus, although alleles in the MOG gene may be in linkage disequilibrium with a locus that contributes to reading disability, it is unlikely that the MOG gene itself is involved.
Smith
S D
SD
Center for Human Molecular Genetics, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha 68198-5455, USA.
Kelley
P M
PM
Askew
J W
JW
Hoover
D M
DM
Deffenbacher
K E
KE
Gayán
J
J
Brower
A M
AM
Olson
R K
RK
D000293:Adolescent; D002648:Child; D002896:Chromosomes, Human, Pair 6; D003434:Crossing Over, Genetic / Q000235:genetics; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007360:Intelligence / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype
D005819:Genetic Markers; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein