Characterization of simple sequence repeat variants linked to candidate genes for behavioral phenotypes

Abstract

Simple sequence repeats (SSRs) have traditionally been used as markers in gene mapping studies and typing for forensic purposes. Recently there has been some speculation that this type of genetic variation also plays a more direct role in influencing gene expression and hence complex phenotypic outcomes such as human behavior. For this reason it is interesting to investigate SSRs linked to candidate genes for various complex phenotypes. An economical multiplex PCR-based assay was designed to simultaneously genotype individuals at 15 loci across 10 candidate genes for human behavioural phenotypes, including seven loci previously unreported in Caucasians (five unreported in any population). All loci were tested for Hardy-Weinberg equilibrium and for two-locus Linkage Disequilibrium. Ewens-Watterson neutrality testing indicated possible selection at a previously unreported DRD2 locus.

Allele frequencies of AVPR1A and MAOA in the Afrikaner population

“…To complicate matters further, different studies have used primers that result in different sized amplicons. Working from the sequence published by Thibonnier et al 26 (AF208541), primer sets can result in an amplicon of 260 bp 41 , 324 bp 25,28,32,37 (and the present study), 316 bp [29][30][31]33,38,39 or 317 bp 34 , while others do not report primers used 36 . Fortunately, the allele spectrum for Caucasoids has a very characteristic profile that can be used to slide the alleles along so that they align well (compare Figure 1a and 1b).…”

Association analysis of 15 polymorphisms within 10 candidate genes for antisocial behavioural traits

“…Although one group has reported an association of the TFAP2B (ACAA) polymorphism with personality traits (Damberg et al, 2000), this study is the first to report an association of the TFAP2B (TC) locus with behavioural traits, in which women with the short/long form of the polymorphism were found to score higher for antisocial traits. Interestingly, the TFAP2B (ACAA) locus, which was found to be in strong linkage disequilibrium with the TFAP2B (TC) polymorphism in this sample (Prichard and Easteal, 2006) also showed a similar nonsignificant trend (P = 0.09) in which women with the short/long TFAP2B (ACAA) genotype also scored higher for antisocial traits. The consistency of the result across the two loci in linkage disequilibrium, and its survival after correction for multiple testing suggests that this association may be genuine.…”

“…Caucasian participants (N = 2096, men = 1007, women = 1089) were genotyped at 15 variable sequence repeat loci [AR (GCA), AVPR1A (TG)x(TC)y, AVPR1A (AGAT), DBH (TG), DRD2 (GA), DRD2 (GT), ESR1 (TG), LMX1B (TG), LMX1B (CA), MAOA 30 bp repeat, NR4A2 (CGG), NR4A2 (AC), OXTR (CA), TFAB2B (ACAA), TFAP2B (TC)] using a multiplex design where all 15 loci were amplified by PCR and separated by capillary electrophoresis simultaneously, using an ABI 3730 genetic analyser (Biomolecular Resource Facility, JCSMR, ANU; Biomolecular Resource Facility, John Curtain School of Medical Research, Australian National University, Canberra, Australia, SPSS version 12, Chicago, USA). Primer sequences, reagents, details of each polymorphism, and genotyping methods have been reported elsewhere (Prichard and Easteal, 2006).…”

AVPR1A andOXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans

“…Caucasian males (N=1005) and females (N=1080) were genotyped at the two AVPR1A loci [NM_000706.3: c.-5518 AVPR1A (TC)x(TG)y (NB: this is a complex mutation with both dinucleotide repeats exhibiting variation), c.-2481 AVPR1A (AGAT)7_16] and one OXTR locus [NM_000916.3: 1170*712 OXTR (CA)10_15] as part of a custom fragment analysis multiplex assay described previously (Prichard and Easteal, 2006). As low frequency variants were detected at all loci, it was necessary to group alleles similar size together to render statistical analysis more manageable.…”