A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia

被引:72
作者
Marino, C
Giorda, R
Lorusso, ML
Vanzin, L
Salandi, N
Nobile, M
Citterio, A
Beri, S
Crespi, V
Battaglia, M
Molteni, M
机构
[1] Sci Inst Eugenio Medea, Dept Child Psychiat, I-23842 Bosisio Parini, LC, Italy
[2] Sci Inst Eugenio Medea, Mol Biol Lab, I-23842 Bosisio Parini, LC, Italy
[3] Sci Inst Eugenio Medea, Dept Neuropsychol, I-23842 Bosisio Parini, LC, Italy
[4] Univ Vita Salute San Raffaele, IRCCS San Raffaele, Dept Psychol, Milan, Italy
[5] Natl Inst Publ Hlth, Div Epidemiol, Oslo, Norway
关键词
developmental dyslexia; DYX1C1; quantitative analysis; family-based association study;
D O I
10.1038/sj.ejhg.5201356
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We applied a family-based association approach to investigate the role of the DYX1C1 gene on chromosome 15q as a candidate gene for developmental dyslexia ( DD) to 158 families containing at least one dyslexic child. We directly sequenced exons 2 and 10 of the DYX1C1 gene and found eight single nucleotide polymorphism ( SNPs), three of which ( - 3G>A, 1249 G>T, 1259 C>G) were suitable for the genetic analyses. We performed single- and multimarker association analyses with DD as a categorical trait by FBAT version 1.4 and TRANSMIT version 2.5.4 programs. Our sample had a power of at least 80% to detect an association between the selected phenotypes and the informative polymorphisms at a significance level of 5%. The results of the categorical analyses did not support the involvement of the DYX1C1 gene variants in this sample of dyslexics and their relatives. Quantitative and multimarker analyses, which provide greater power to detect loci with a minor effect, consistently yielded nonsignificant results. While D1X1C1 is a good candidate gene for DD, we were unable to replicate the original findings between DYX1C1 gene and DD, perhaps due to genetic heterogeneity.
引用
收藏
页码:491 / 499
页数:9
相关论文
共 43 条
[1]  
[Anonymous], 1997, Diagnostic and Statistical Manual of Mental Disorders, Vfourth
[2]   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
[3]  
CARDON LR, 1995, SCIENCE, V268, P5217
[4]   A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission [J].
Clayton, D .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (04) :1170-1177
[5]   Transmission/disequilibrium tests for extended marker haplotypes [J].
Clayton, D ;
Jones, H .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (04) :1161-1169
[6]  
CORNOLDI C, 1986, PROVE LETT
[7]  
DRACOPOLI NC, 2004, CURRENT PROTOCOLS HU
[8]  
FACOETTI A, IN PRESS PROGR DYSLE
[9]  
Fagerheim T, 1999, J MED GENET, V36, P664
[10]   A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia [J].
Fisher, SE ;
Marlow, AJ ;
Lamb, J ;
Maestrini, E ;
Williams, DF ;
Richardson, AJ ;
Weeks, DE ;
Stein, JF ;
Monaco, AP .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (01) :146-156