244 II. BIOLOGICAL  FOuNDATIONS
ecules that are found in each cell nucleus of 
the human body.1 Humans carry 22 pairs 
of autosomes and two sex-  specific chromo -
somes (XX for females and XY for males). 
Each chromosome consists of two intercon -
nected strands of nucleotides,  also known as 
the double helix. The nucleotides consist of 
different chemical groups: a sugar molecule, 
a phosphate group, and one of four nitrog -
enous bases : adenine (A), cytosine (C), gua -
nine (G) and thymine (T). Genes  are specific 
sequences of nucleotides that are functional 
and code for proteins via the processes of 
transcription and translation ( gene expres-
sion). The human genome carries approxi -
mately 20,000–25,000 genes. Ninety-  nine 
percent of the human genome is identical for 
all humans. The remaining 0.01% contains 
the genetic variation that create the individ -
ual differences among humans.
Measuring Genetic  Variation
In molecular genetics studies, different types 
of genetic variation are distinguished and 
measured. Single-  nucleotide polymorphisms 
(SNPs) are an important type of genetic 
variation that represent loci where individu -
als vary on one single nucleotide (e.g., some 
humans have A on this location, while oth -
ers have C). Most SNPs are biallelic, that is, 
just two variants occur in a specific popula -
tion. SNPs are commonly used in candidate 
gene and genomewide genetic association 
studies. Another type of genetic variation 
is represented by variable number tandem 
repeats (VNTRs), in which a sequence of 
nucleotides is repeated a variable number of 
times. VNTRs are sometimes also called mi -
crosatellites. The sequence of nucleotides is 
usually rather small (two to 10 nucleotides) 
and is commonly repeated between two and 
50 times. Together with SNPs, VNTRs are 
used in candidate gene association studies. 
VNTRs are also used in genetic linkage 
studies.2
Molecular Genetics Studies of Personality
Linkage  Studies
Genetic linkage studies examine how a ge -
netic marker cosegregates with a trait (or 
disease) within families. It uses the prin -ciple of genetic linkage; loci close together 
are said to be “linked.” Alleles at loci close 
together on the genome tend to be inherited 
together, because the chance of a recombi -
nation event for two loci close together is 
very small (Ferreira, 2004). For example, 
in pairs of siblings, one may test whether 
an increased sharing of a marker inherited 
from the same parent predicts resemblance 
for a personality trait (Haseman & Elston, 
1972). Genomewide linkage analysis uses 
multiple markers along the genome. A hand -
ful of genomewide linkage studies has been 
conducted for personality, the first of which 
appeared in 1998 (Cloninger et al., 1998). 
Most studies focused on neuroticism (Ful -
lerton et al., 2003; Kuo et al., 2007; Nash 
et al., 2004; Neale, Sullivan, & Kendler, 
2005). Another study included, besides neu -
roticism also extraversion, psychoticism 
and lying (Gillespie et al., 2008), and one 
study has been conducted for the traits harm 
avoidance, reward dependence, and novelty 
seeking (Cloninger et al., 1998). These stud -
ies identified several candidate regions, but 
many of those regions could not be repli -
cated across studies. The study by Fullerton 
et al. (2003) identified a region on chromo -
some 12q for neuroticism, which showed 
suggestive linkage in the studies by Kuo et 
al. (2007) and Gillespie et al. (2008). Ful -
lerton et al. (2003) further identified two re -
gions on chromosome 1 (on 1q and on 1p for 
females specifically). The 1p region was also 
found in the study by Nash et al. (2004), 
and the 1q region also appeared in Neale et 
al. (2005), although it should be noted that 
the locations are not exactly the same, and 
the peaks at these regions were not signifi -
cant genomewide. The study by Cloninger 
et al. (1998) found a genomewide significant 
peak on chromosome 8p for harm avoid -
ance, but nonsignificant results for reward 
dependence and novelty seeking. The peak 
for harm avoidance was replicated in an 
independent study focusing on three chro -
mosomal regions including 8p (Zohar et al., 
2003). The linkage findings for neuroticism 
did not overlap with the findings for harm 
avoidance, despite the strong phenotypic 
and genetic overlap (Gillespie, Johnstone, 
Boyce, Heath, & Martin, 2001).
In brief, genomewide linkage studies 
have not been very successful in robustly 