Biology Reference
In-Depth Information
Many statistical tests have been developed to calculate the deviation of the allelic
frequencies from HWE. These include the goodness-of-fit test (also called the chi
square test), homozygosity test, likelihood ratio test and the exact test [19, 20].
However, when analysing polymorphic STR loci these tests do not have the required
sensitivity because there are many undetected genotypes and numerous genotypes
that are detected at very low frequencies at each locus. The multi-locus exact test was
developed and can detect deviation from HWE when a large dataset is tested [21, 22].
Significant deviations from HWE have not been detected in the vast majority of
populations, including some with high levels of consanguinity [23 - 25]. An exact
test will not detect variations from HWE in small datasets, unless the deviation is
extreme, and therefore conclusions from performing the exact test should not be
over interpreted.
Estimating the frequencies of STR profiles
In forensic DNA analysis the HWE is used along with an allele frequency database
to calculate genotype frequencies. An allelic frequency database is constructed by
measuring the occurrence of alleles within the defined population. It has been rec-
ommended that a database of at least 200 alleles per locus (or 100 individuals) be
used for a particular population when using the database for generating the statis-
tical estimates of the strength of DNA evidence [26]. The larger the database, the
more representative of the population it will be, and current practice dictates that
several hundred individuals should be sampled when creating an allelic frequency
database [27]. These people should not be direct relations; therefore siblings or
mother and child, and so on combinations should not be incorporated into an allele
frequency database.
Using the HWE, the expected genotype frequency at each locus is calculated
using the observed allele frequencies. Using these frequencies along with the above
HWE equations, we can calculate the frequency of a STR profile. If we take the
profile that was analysed in Chapter 6, the genotype proportions for each locus are
calculated using
p
2
for the homozygote and 2
pq
for the heterozygote loci (Table 8.1).
The overall profile frequency is calculated by multiplying the genotype frequency at
each locus. This multiplication is termed the product rule; it is possible because the
inheritance of alleles at each locus is independent of the other loci.
There have been some challenges to the approach presented above, namely that the
inaccurate estimation of allelic frequencies can lead to inaccurate profile frequency
estimates. To overcome this problem several methods have been employed that take
into consideration the limitations in allele frequency estimates.
Corrections to allele frequency databases
Allelic frequencies are calculated by measuring a number of alleles in the target
population. The more alleles that are measured as a part of the allelic frequency
database the more accurate it will be. However, it is impracticable to measure all of
