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There are three outcomes that will result when STR interpretation is performed. There is
a match, no match, and inconclusive. The only result that requires statistics is a match. Statistics
are mathematically calculated to determine the estimate of a random match probability of that
sample occurring between two unrelated people. The estimate requires knowledge and testing of
allele frequency from different racial/ethnic samples. There is not one universal standard when it
comes to a statistical solution, however, there are methods that are more frequently utilized, and
those tests are recommended by NRCII and DAB.
Probability is the number of times something actually occurs divided by the amount of
times it has the opportunity to happen. It is viewed on a continuum between zero and one.
Probabilities are described mathematically with symbols. There are three laws of probability
1. Probabilities can take place in the range of zero to one
2. Events can be mutually exclusive, meaning that if any one of a particular set of events
has occurred, then none of the others has occurred.
3. When two events are independent of one another, their probabilities can be multiplied
with one another.
Likelihood ratios are comparisons made between the Null Hypothesis and the Alternative
Hypothesis. The Null Hypothesis can be described as a hypothesis indicating that a difference
does not exist. The Alternative Hypothesis suggests that a difference does exist.
There are six steps involved in making a statistical analysis of a hypothesis, they are as
follows;
1. formulate two competing hypothesis
2. select appropriate model that identifies the test statistic
3. determine level of significance (measure of risk)
4. collect a sample and calculate an estimate of the test statistic
5. define the region of rejection
6. select the appropriate hypothesis
There are two types of errors that can occur in hypothesis testing. Type I involves
rejecting the hypothesis when in fact it is really true. Type II Error involves accepting the
hypothesis when in fact it is really false.
The Chi Square test is known as the “goodness to fit” test because it is the sum of the
squared value between the observed results and the expected results divided by the expected
value. The results of this are charted and compared to determine the deviation from the expected
normal values. The differences the numbers are known as the degrees of freedom.
Using the confidence intervals will help in determining the precision of a point estimate.
They are usually measured on a 95% confidence interval, which is the sample average give, or
take two standard deviations. The confidence interval is a function of frequency of the
individuals in population and the observation.
Randomization tests are to help ask questions when collecting data that comes out
differently and to confirm the validity of the data. There are two different ways to retest the
samples, bootstrapping and jack-knifing. Bootstrapping is a computer simulation where the
sample being retested is a replacement of the original observation. Jack-knifing involves
creating a new sample that is one less than the original observation.
The study of inherited variation is known as population genetics, this is the observation
with different population groups in genotype frequencies and alleles. The alleles have two
copies of autosomal genes, one from the mother or egg and one from the father or sperm. When
there is a difference between the two alleles there are known as heterozygous. For example A
from mom and a from dad creating Aa. When two alleles come together and they are identical
they are known as homozygous. For example B from mom and B from dad creating BB. There
is variability within the alleles, which helps determine the stability of that allele being passed on
to the next generation. Forces in the population genetic are mutations, migration, natural
selection, and random genetic drift that affect gene frequency of alleles present in the population.
Laws of Mendelian Genetics:
1. Law of segregation - two members of a gene pair segredate from each other during sex
cell formation
2. Law of independent assortment - different segregating gene pairs behave independently.
Both laws used in Hardy-Weinberg equilibrium (HWE). Using a Punnett Square, each
allele frequency can be calculated based on either the observed characteristics of offspring or the
original characteristics of the parents. The relationship between the number of alleles and the
number of possible genotypes can be expressed by n(n + 1)/2.
Comparisons between two or more sets of alleles may be performed with R×C
contingency tables, which involve showing the response of one variable as a function of another
variable.
To understand the numbers used in population data publication can be used to relative
each STR maker which has been typed, the measures of the evaluated DNA makers include
Power Discrimination(PD), the power of exclusion(PE), the a priori chance of exclusion(CE),
the polymorphism information content (PIC), and a marker’s heterozygousity(H).
The “best” markers typically use STR markers, European laboratories largely using SGM
Plus kit that amplifies 10 STR loci and North American laboratories use 13 core CODIS loci.
The eight STR is common between European and North America STR testing sets: FGA,
TH01, VWA, D3S1358, D8S1179, D16S539, D18S51, and D21S11.these provide a useful
measure for evaluating the discriminating power of the DNA profiling system.
The most common type can be calculated by considering a sample type that is
heterozygous at all loci processing the two most common alleles at each locus.
Ch 20
A population DNA database is used to find common alleles present in the population
under consideration and is often done by getting healthy, unidentified samples from a blood bank
or local hospital, ideally of unrelated individuals of known ethnicity. PCR amplification is done
on the extracted samples and genotyped at the STR loci of interest, and the allele frequency is
found. 100-120 individuals per locus per population is sufficient for robust likelihood
calculations.
Institutions require approval from the Institutional Review Board (IRB) when testing a
subject. The board needs consent by those being tested or the testing is completely anonymous
and the genetic information cannot be linked to the subject.
When STR genotypes are generated, the sample data is evaluated to ensure that the
database is working for human tests. Many computer programs are now available to test the
independence of statistical tests on genetic data. When testing various tests for independence a
computer program from Ranajit Chakraborty’s group from the University of Cincinnati has a
system called DNATYPE. The system checks for errors, accuracy, and also searches for
duplicates of alleles. Program H in DNATYPE examines that the distribution of genotypes are in
frequencies of Hardy-Weinberg equilibrium.
HWE predicts the stability of alleles; the purpose is to test if alleles within a locus are
independent. Frequencies should not change if the locus is genetically stable, however; natural
populations may violate the HWE and change over time. Other purpose of HWE test is for
indications of excess homozygote; this can happen due to allelic dropout. Allele frequencies
might generate expected genotype frequencies when observed. When observed and the expected
value is similar it is said that those alleles in the genetic locus value are stable, therefore “in
equilibrium.”
Three important reasons for departure from the Hardy-Weinberg equilibrium are (1)
parents might be related to one another leading to inbreeding, (2) population structure and (3)
selection since surviving genotypes reproduce at different rates.
For random matching probabilities the loci needs to be independent. Linkage Equilibrium occurs
when STR loci is transferred independently during DNA segment meiosis.
Random match probabilities are equated respectively with the DNA profile of interest.
This test population is tested based on alleles frequencies. Deviations from independence are rare
and found in the 13 CODIS STRs because they are located on different chromosomes except for
CSF1PO and D5S818. If independence can be shown between alleles and loci, we can use the
product rule to show random match probabilities.