Family-based association mapping provides evidence for a gene for reading disability on chromosome 15q.

Family-based association mapping was used to follow up reports of linkage between reading disability (RD) and a genomic region on chromosome 15q. Using a two-stage approach, we ascertained 101 (stage 1) and 77 (stage 2) parent-proband trios, in which RD was characterized rigorously. In stage 1, a set of eight microsatellite markers spanning the region of putative linkage was used and a highly significant association was detected between RD and a three-marker haplotype (D15S994/D15S214/D15S146: P and empirical P < 0.001). A significant association with the same three-marker haplotype was also observed in the second-stage sample (P = 0.009, empirical P = 0.006). Our data therefore provide strong evidence for one or more genes contributing to RD being located in the vicinity of the region including D15S146 and D15S994. In addition, our results provide support for association analysis being a useful method to map susceptibility loci for complex disorders.

[1]  H. Inoko,et al.  Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene. , 1999, Human molecular genetics.

[2]  H. Lubs,et al.  A new gene (DYX3) for dyslexia is located on chromosome 2 , 1999, Journal of medical genetics.

[3]  L. Kruglyak.  Prospects for whole-genome linkage disequilibrium mapping of common disease genes , 1999, Nature Genetics.

[4]  J. Stevenson,et al.  The structure of genetic influences on general cognitive, language, phonological, and reading abilities. , 1999, Developmental psychology.

[5]  R. Straub,et al.  Marker-to-marker linkage disequilibrium on chromosomes 5q, 6p, and 8p in Irish high-density schizophrenia pedigrees. , 1999, American journal of medical genetics.

[6]  K. Weiss,et al.  Linkage disequilibrium mapping of complex disease: fantasy or reality? , 1998, Current opinion in biotechnology.

[7]  J. Todd,et al.  Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13. , 1998, American journal of human genetics.

[8]  S. Cichon,et al.  Evidence for linkage of spelling disability to chromosome 15. , 1998, American journal of human genetics.

[9]  J. Todd,et al.  Transmission of haplotypes of microsatellite markers rather than single marker alleles in the mapping of a putative type 1 diabetes susceptibility gene (IDDM6). , 1998, Human molecular genetics.

[10]  W J Ewens,et al.  The TDT and other family-based tests for linkage disequilibrium and association. , 1996, American journal of human genetics.

[11]  N Risch,et al.  The Future of Genetic Studies of Complex Human Diseases , 1996, Science.

[12]  A. Hagell,et al.  Poor readers in adulthood: Psychosocial functioning , 1996, Development and Psychopathology.

[13]  Richard S. J. Frackowiak,et al.  Is developmental dyslexia a disconnection syndrome? Evidence from PET scanning. , 1996, Brain : a journal of neurology.

[14]  D. Curtis,et al.  An extended transmission/disequilibrium test (TDT) for multi‐allele marker loci , 1995, Annals of human genetics.

[15]  N. Freimer,et al.  The distribution of linkage disequilibrium over anonymous genome regions. , 1995, Human molecular genetics.

[16]  C Donlan,et al.  GENETIC BASIS OF SPECIFIC LANGUAGE IMPAIRMENT: EVIDENCE FROM A TWIN STUDY , 1995, Developmental medicine and child neurology.

[17]  D W Fulker,et al.  Quantitative trait locus for reading disability on chromosome 6. , 1994, Science.

[18]  I. Borecki,et al.  Commingling and segregation analysis of reading performance in families of normal reading probands , 1994, Behavior genetics.

[19]  M. Owen,et al.  The genetic basis of complex human behaviors. , 1994, Science.

[20]  H. Lubs,et al.  Suggestive linkage of developmental dyslexia to chromosome 1p34-p36 , 1993, The Lancet.

[21]  B. Shaywitz,et al.  Discrepancy Compared to Low Achievement Definitions of Reading Disability , 1992, Journal of learning disabilities.

[22]  J. Stevenson.  Which aspects of processing text mediate genetic effects? , 1991 .

[23]  Sandra A. Smith,et al.  Evidence for major gene transmission of developmental dyslexia. , 1991, JAMA.

[24]  D. Fulker,et al.  Specific Deficits in Component Reading and Language Skills , 1989, Journal of learning disabilities.

[25]  D. Fulker,et al.  Evidence for a genetic aetiology in reading disability of twins , 1987, Nature.

[26]  H. Eiberg,et al.  Dyslexia and chromosome 15 heteromorphism: negative lod score in a Danish material , 1987, Clinical genetics.

[27]  P Graham,et al.  A twin study of genetic influences on reading and spelling ability and disability. , 1987, Journal of child psychology and psychiatry, and allied disciplines.

[28]  B. Pennington,et al.  Specific reading disability: identification of an inherited form through linkage analysis. , 1983, Science.

[29]  H. K. Lewis.  Letter-, Word- and Mind-Blindness , 1900, Bristol Medico-Chirurgical Journal (1883).

[30]  Joan,et al.  Evidence for a genetic aetiology in reading disability of twins , 2002 .

[31]  J. Lamb,et al.  A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia. , 1999, American journal of human genetics.

[32]  E L Grigorenko,et al.  Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. , 1997, American journal of human genetics.

[33]  Peter Beighton,et al.  de la Chapelle, A. , 1997 .

[34]  J. Todd,et al.  Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31–q33 , 1995, Nature Genetics.

[35]  B. Pennington,et al.  Dyslexia subtypes: genetics, behavior, and brain imaging. , 1988, Research publications - Association for Research in Nervous and Mental Disease.