DNA commission of the International Society of Forensic Genetics: Recommendations on the interpretation of mixtures.

The DNA commission of the International Society of Forensic Genetics (ISFG) was convened at the 21st congress of the International Society for Forensic Genetics held between 13 and 17 September in the Azores, Portugal. The purpose of the group was to agree on guidelines to encourage best practice that can be universally applied to assist with mixture interpretation. In addition the commission was tasked to provide guidance on low copy number (LCN) reporting. Our discussions have highlighted a significant need for continuing education and research into this area. We have attempted to present a consensus from experts but to be practical we do not claim to have conveyed a clear vision in every respect in this difficult subject. For this reason, we propose to allow a period of time for feedback and reflection by the scientific community. Then the DNA commission will meet again to consider further recommendations.

Symbolic kinship program.

This paper discusses a computerized algorithm to derive the formula for the likelihood ratio for a kinship problem with any arbitrarily defined relationships based on genetic evidence. The ordinary paternity case with the familiar likelihood formula 1/2q is the commonest example. More generally, any miscellaneous collection of people can be genetically tested to help settle some argument about how they are related, what one might call a "kinship" case. Examples that geneticists and DNA identification laboratories run into include sibship, incest, twin, inheritance, motherless, and corpse identification cases. The strength of the genetic evidence is always described by a likelihood ratio. The general method is described by which the computer program finds the formulas appropriate to these various situations. The benefits and the interest of the program are discussed using many examples, including analyses that have previously been published, some practical problems, and simple and useful rules for dealing with scenarios in which ancestral or fraternal types substitute for those of the alleged father.

Distinguishing minisatellite mutation from non-paternity by MVR-PCR.

Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) was devised to map the interspersion pattern of subtle variant repeats along minisatellite tandem arrays. MVR-PCR has revealed enormous diversity of allele structures at several loci, far more than can be resolved by allele length analysis. We have reported the application of MVR-PCR at minisatellite MS32 (D1S8) and MS31A (D7S21) in a paternity case lacking a mother and showed that it resulted in higher paternity probabilities than for a set of 12 other DNA markers including six STRs. Hypervariable minisatellites like MS32 and MS3lA can however, show significant germline mutation rates to new length alleles which can generate false exclusions in paternity cases although paternity cases showing mutant paternal alleles at more than one locus will be rare when several MVR loci are examined. Detailed knowledge of mutation processes coupled with MVR analysis of allele structure can help distinguish mutation from non-paternity. We now show how similar mutant alleles are to their progenitors using both real and simulated data, and demonstrate how MVR-PCR can be used to identify mutant paternal allele in paternity cases showing apparent exclusions.

A note on paternity computation in cases lacking a mother.

When the mother is unavailable for parentage testing, a calculation must usually be based on types determined for the child and the alleged father. Particularly in the case of DNA typing, the formula is easy to derive. The correct formula is apparently not widely known, however, and in fact, a formula that is obviously incorrect seems often to be used and quoted. The correct method of derivation is indicated, and formulae are given for the various possibilities for patterns of gene-sharing between child and alleged father. In most cases paternity = 1/4Pr(shared allele) is an adequate formula.

Issues and strategies in the DNA identification of World Trade Center victims.

Identification of the nearly 3000 victims of the World Trade Center attack, represented by about 15,000 body parts, rests heavily on DNA. Reference DNA profiles are often from relatives rather than from the deceased themselves. With so large a set of victims, coincidental similarities between non-relatives abound. Therefore considerable care is necessary to succeed in correlating references with correct victims while avoiding spurious assignments. Typically multiple relatives are necessary to establish the identity of a victim. We describe a 3-stage paradigm--collapse, screen, test--to organize the work of sorting out the identities. Inter alia we present a simple and general formula for the likelihood ratio governing practically any potential relationship between two DNA profiles.

Calculation of paternity probabilities from multilocus DNA profiles.

We describe a procedure for evaluation of paternity evidence from multi-locus DNA probe patterns. A computer program abstracts a "+/-" notation description from the multilocus profile and then calculates a paternity index based on observed phenotypic fragment frequencies. The biostatistical evaluation considers only bands found in the child and missing from the mother--a simplified approach that is at once robust and conservative. Mutations are of course taken into account. Particular features lending objectivity to the interpretation include computer reading and matching decisions, and specific recognition and statistical compensation for ambiguities ("faint orphans").

Likelihood ratios for mixed stains when the number of donors cannot be agreed.

Suppose that part of the prosecution's evidence in some crime case is analysis of a blood stain, and that the traits E discovered in the stain suggest multiple donors. Then the prosecution will probably allege some specific inculpatory hypothesis H0 about the sources of the stain, and P (E [symbol: see text] H0) can be calculated. It is desirable to use this as the numerator of a likelihood ratio. However, in general the obvious denominator P (E [symbol: see text] approximately H0) cannot be calculated, so unless the defense is sufficiently obliging as to stipulate to a specific choice among the potentially infinite number of more or less exculpatory alternative hypotheses, the desired likelihood ratio can't be evaluated. We show that nonetheless, in most cases there is an adequate inequality.