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A novel A/G SNP in the −615th position of the dopamine D4 receptor promoter region as a source of misgenotyping of the −616 C/G SNP

2003; Wiley; Volume: 126B; Issue: 1 Linguagem: Inglês

10.1002/ajmg.b.20112

1552-485X

Zsolt Rónai, Eszter Szántai, Richárd Szmola, Zsófia Nemoda, Anna Székely, Judit Gervai, András Guttman, Mária Sasvári‐Székely,

Autism Spectrum Disorder Research

Abstract The polymorphic 5′ upstream region of the dopamine D4 receptor ( DRD4 ) gene containing several single nucleotide polymorphisms (SNPs) has recently become a focus of association studies in psychiatric genetics. Most SNP genotyping methods are based on the two‐step procedure of restriction fragment length polymorphism (RFLP). An alternative technique is a single‐step method of allele‐specific amplification (ASA), previously introduced for genotyping the −521 C/T SNP of the DRD4 promoter region and applied here for the −616 C/G SNP. Parallel genotyping of individuals with the novel ASA method and the conventionally used Ava II RFLP showed a potential underestimation of the −616 GG genotype frequency by the conventional method. Sequencing the dubious samples clearly demonstrated a novel A/G SNP at the −615th position influencing the Ava II digestion and thus resulting in misgenotyping. To avoid this problem, we introduced the Sau96 I RFLP for the −616 C/G genotyping as this restriction enzyme is not sensitive for the −615 A/G sequence variation. Allele (−616 G = 0.48; −616 C = 0.52) and genotype (−616 GG = 0.25; −616 GC = 0.46; −616 CC = 0.29) frequencies were determined by both the novel ASA and the Sau96 I methods. The obtained genotype frequencies corresponded to the Hardy–Weinberg equilibrium in our healthy Caucasian sample (N = 534, P = 0.168). Using these methods, no association was found between the −616 C/G SNP and personality factors of Cloninger's temperament and character inventory (N = 153) in our population. © 2003 Wiley‐Liss, Inc.