A dyslexia susceptibility locus (DYX7) linked to dopamine D4 receptor (DRD4) region on chromosome 11p15.5

被引:60
作者
Hsiung, GYR
Kaplan, BJ
Petryshen, TL
Lu, S
Field, LL
机构
[1] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada
[2] Univ Calgary, Dept Pediat, Calgary, AB T2N 1N4, Canada
[3] MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA
关键词
phonological coding; dyslexia; reading disability; genetics; linkage analysis; dopamine receptor D4; DRD4; HRAS;
D O I
10.1002/ajmg.b.20082
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Dyslexia is a disability in acquiring reading and spelling skills that is independent of general intelligence and educational opportunity, and is highly heritable. It is known that dyslexia often co-occurs with attention deficit hyperactivity disorder (ADHD), and the 7-repeat allele of the 48-bp tandem repeat in exon 3 of the dopamine D4 receptor (DRD4) has been implicated in ADHD. We, therefore, investigated DRD4 as a candidate gene for dyslexia by testing for linkage and association with 14 markers at and around the DRD4 locus on chromosome 11p15.5. Using 100 families having at least two siblings affected with dyslexia, model-free linkage analysis revealed evidence for linkage to the DRD4-exon 3 repeat (two-point MFLOD = 2.27, P = 0.001) and to HRAS located just proximal to DRD4 (two-point MFLOD = 2.68, P = 0.0004). Evidence for linkage was maximal between DRD4 and HRAS (three-point MFLOD = 3.57, P = 0.00005). However, linkage disequilibrium analysis showed no significant evidence for association between dyslexia and DRD4 or HRAS. In particular, dyslexic subjects showed no significant increase of the DRD4 7-repeat allele associated with ADHD. It is possible that other DRD4 variants, not in strong linkage disequilibrium. with the exon 3 repeat polymorphism, or alternatively, another gene very closely linked to DRD4, may influence susceptibility to dyslexia. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:112 / 119
页数:8
相关论文
共 101 条
[1]  
ASGHARI V, 1994, MOL PHARMACOL, V46, P364
[2]   MODULATION OF INTRACELLULAR CYCLIC-AMP LEVELS BY DIFFERENT HUMAN DOPAMINE D4 RECEPTOR VARIANTS [J].
ASGHARI, V ;
SANYAL, S ;
BUCHWALDT, S ;
PATERSON, A ;
JOVANOVIC, V ;
VANTOL, HHM .
JOURNAL OF NEUROCHEMISTRY, 1995, 65 (03) :1157-1165
[3]   DRD4 related to infant attention and information processing: a developmental link to ADHD? [J].
Auerbach, JG ;
Benjamin, J ;
Faroy, M ;
Geller, V ;
Ebstein, R .
PSYCHIATRIC GENETICS, 2001, 11 (01) :31-35
[4]   COMORBIDITY OF ADHD AND READING-DISABILITY AMONG CLINIC-REFERRED CHILDREN [J].
AUGUST, GJ ;
GARFINKEL, BD .
JOURNAL OF ABNORMAL CHILD PSYCHOLOGY, 1990, 18 (01) :29-45
[5]   QUANTITATIVE TRAIT LOCUS FOR READING-DISABILITY ON CHROMOSOME-6 [J].
CARDON, LR ;
SMITH, SD ;
FULKER, DW ;
KIMBERLING, WJ ;
PENNINGTON, BF ;
DEFRIES, JC .
SCIENCE, 1994, 266 (5183) :276-279
[6]  
Castor GS, 1998, ADV BOUND ELEM SER, V4, P3
[7]   A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission [J].
Clayton, D .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (04) :1170-1177
[8]   Studies of the c-Harvey-Ras gene in psychiatric disorders [J].
Comings, DE ;
Wu, SJ ;
Chiu, C ;
Muhleman, D ;
Sverd, J .
PSYCHIATRY RESEARCH, 1996, 63 (01) :25-32
[9]   Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1 [J].
Costa, RM ;
Federov, NB ;
Kogan, JH ;
Murphy, GG ;
Stern, J ;
Ohno, M ;
Kucherlapati, R ;
Jacks, T ;
Silva, AJ .
NATURE, 2002, 415 (6871) :526-530
[10]  
COTTINGHAM RW, 1993, AM J HUM GENET, V53, P252