15The size of genomes isolated from mouse liver tissues increases with age, peaking
at 5 weeks and the copy number of several retro-element sub-families are up to
twofold higher in liver tissue than in lung or spleen tissue (Lee et al. 2012 ). The
fi ndings that the genome structure of an individual is variable depending on age and
organ type in association with the transposition of retroelements may have broad
implications in understanding biologic phenomena. Data from this study indicate
that there may be multiple variant isoforms of an individual. This fi nding indicates
that a new protocol or system and more research will be needed to analyze and make
sense of how the structural changes in the genome relate to an individual’s health. It
has implications for personalized medicine. Further work is required to pinpoint
which structural changes in the genome correlate to a particular disease process and
this might eventually provide clinicians with new prognostic biomarkers.
Structural Variations in the Human Genome
Structural changes are extremely common in human populations. Genetic variation
among individual humans occurs on many different scales, ranging from gross alter-
ations in the human karyotype to a SNP. More bases are involved in structural
changes in the genome than are involved in single-base-pair changes.
Although the original human genome sequencing effort was comprehensive, it
left regions that were poorly analyzed. Later investigations revealed that, even in
healthy individuals, many regions in the genome show structural variations (SVs),
which involve kilobase- to megabase-sized deletions, duplications, insertions, inver-
sions, and complex combinations of rearrangements. A study offers a new view of
what causes the greatest genetic variability among individuals − suggesting that it is
due less to single point mutations than to the presence of structural changes that
cause extended segments of the human genome to be missing, rearranged or present
in extra copies (Korbel et al. 2007 ). This study was designed to fi ll in the gaps in the
genome sequence and to create a technology to rapidly identify SVs between
genomes at very high resolution over extended regions. A novel DNA-based method
called Paired-End Mapping was used for this study. Researchers broke up the
genome DNA into manageable-sized pieces about 3,000 bases long; tagged and
rescued the paired ends of the fragments; and then analyzed their sequence with a
high-throughput, rapid-sequencing method developed by 454 Life Sciences. This
method of sequencing can generate hundreds of thousands of long read pairs, which
are unique within the human genome, to quickly and accurately determine genomic
variations. Whereas previous studies, based on point mutations estimated that there
is a 0.1 % difference between individuals, this work points to a level of variation
between 2 and 5 times higher. There were ‘hot spots’, i.e. regions with a lot of varia-
tion, which are often regions associated with genetic disorder and disease. These
results will have an impact on how genetic effects in disease are studied. It was
previously assumed that ‘landmarks,’ like the SNPs, were fairly evenly spread out
in the genomes of different people. Now, one has to take into account the SVs can
distort the map and differ between individual patients. Even in healthy persons,
Molecular Biological Basis of Personalized Medicine