Kinship testing

19 Apr

Kinship testing
The application of DNA profiling to kinship analysis is widespread and offers an easy means of establishing biological relationships. Not surprisingly, paternity testing is the most common form of kinship testing, with hundreds of thousands of tests being performed worldwide each year [1]. Since the first DNA based kinship test in 1985 [2], DNA analysis has been applied to larger numbers of kinship tests, to the testing of more complex relationships and to the identification of highly compromised human remains.

Paternity testing
PCR-based STR profiling has now become the standard tool and the PowerPlex® 16 (Promega) and AmpFISTR® Identifiler® (Applied Biosystems) STR kits that can analyse 15 loci simultaneously are routinely used (see Chapter 6). Laboratories that undertake kinship testing often have over 20 genetic markers at their disposal, including STR markers on the X and Y chromosomes [3], that allow for the testing of complex relationships [4]. The sensitivity of STR analysis, while not essential for most forms of paternity testing, allows samples to be routinely collected using buccal swabs [1] and has expanded the possible scenarios where it can be used, for example, the analysis of low amounts of DNA recovered from foetal cells [5, 6] (Figure 11.1). The methodology used to produce DNA profiles for paternity testing is identical to the analysis of material recovered from crime scenes (see Chapters 4 to 7). The interpretation of results is more complex than when comparing profiles from crime scenes and suspects. If the tested man does not possess the alleles that have been inherited from the biological father we can conclude that he cannot be the biological father. However, because mutations between the father and child could lead to a false exclusion at any given loci [1, 7-10], it is standard practice is to require an exclusion at three or more loci before a test is declared negative. If we cannot exclude the tested man as being the biological father then we have to assign a value to indicate the significance of non-exclusion. Likelihood ratios (see Chapter 9), which consider two competing, and mutually exclusive hypotheses are

Figure 11.1 A STR profile generated from foetal cells recovered from amniotic fluid in early preg-nancy. In this case it was possible to determine that pregnancy had resulted from a rape, and allowed an informed decision to be made on whether or not to have the foetus aborted. The profile was generated using the AmpFISTR® Profiler Plus® STR kit (Applied Biosystems) (see plate section for full-colour version of this figure)
used. The hypotheses are:

The symbols Hp and Hd were introduced in Chapter 9 when comparing the proposition or hypothesis put forward by the prosecution (Hp) compared with the hypothesis put forward by the defence (Hd), although in many civil cases the terms prosecution and defence are not appropriate. This likelihood is called a paternity index (PI) and can be assessed using equation (11.1).

where Pr is probability. To calculate this likelihood ratio, we compare the probability of the child’s genotype (Gc) given the mother’s (Gm) and tested man’s genotype (Gtm), if the tested man is the biological father (Hp) and the probability of the child’s genotype given the mother’s and tested man’s genotype, if the tested man is not the biological father (Hd). The numerator and denominator are conditional on the genotypes of the mother, child and tested man. They can be derived using a ‘Punnet square’.

Punnett square
The equations are not difficult to understand, particularly if derived from a Punnett square and converting to text form. Consider the case where the mother is genotype a,b and child is genotype b,c and the alleged father is c,d. If he is the father then the mother must pass on allele b, and the father must pass on allele c. If he is not the father then the mother must still pass on allele b but some other man must pass on allele c. This is given in the Punnett square below.

Random Posts

Comments are closed.