Biology Reference
In-Depth Information
mtDNA to reactive oxygen species that are produced as byproducts in oxidative phos-
phorylation [15]. Direct analysis of mother-to-children transmissions has estimated
that a mutation in the hypervariable regions is passed from mother to child approx-
imately once in every 30 - 40 events. In the vast majority of cases where a mutation
is detected, there is only one base change between the mother and child [16, 17].
Hypervariable regions
In most forensic investigations the aim of DNA profiling is to differentiate between
individuals; therefore, the most polymorphic regions are analysed. Following the
sequencing of the human mtDNA genome it was apparent that the D-loop, also
known as the control region, was not under the same functional constraints as the
rest of the genome. Some blocks within the control region are highly conserved but
large parts are not. Two main regions are the focus of most forensic studies, these are
known as hypervariable sequence regions I and II (HV-I and HV-II) and they contain
the highest levels of variation within the mtDNA genome. Both the hypervariable
blocks are approximately 350 bp long. A third hypervariable region, HV-III has also
been used in some cases. Within the hypervariable regions the rate of mutation is
not constant and some sites are hotspots for mutation, whereas others show much
lower rates of change [18 - 20].
The polymorphic sites are concentrated within relatively small regions of the
mtDNA genome and can be analysed using PCR amplification followed by Sanger
sequencing [21]. Many of the methods used for SNP detection can also be used (see
Chapter 12).
Applications of mtDNA profiling
There are several scenarios where mtDNA is a valuable genetic marker. These are
related to two properties of mtDNA - the high copy number and the maternal inher-
itance. The high copy number is valuable when the amount of cellular material
available for analysis is very small: crime scene material that is commonly profiled
using mtDNA includes hair shafts [22 - 24] and faecal samples [25].
mtDNA is also useful for the analysis of human remains that are highly degraded
and not amenable to standard STR typing [26 - 29]. The maternal inheritance is a
useful trait for human identification when there are no direct relatives to use as a
reference sample; the identification of some of the Romanov family using Prince
Philip and other living relatives as reference samples provides a powerful illustration
of the use of maternal inheritance [30, 31] (Figure 13.2).
A series of historical cases has followed that demonstrates the application of
mtDNA when linking relatives to human remains [32 - 37].
Interpretation of mtDNA profiles
mtDNA is used for both associating crime scene samples with individuals and also in
the identification of human remains. In both cases the profile that has been generated
