EDITORIAL CORRESPONDENCE
Applications of DNA fingerprinting To the Editor: The recent article by McCabe, entitled "Applications of D N A Fingerprinting in Pediatric Practice" (J PEDIATR 1992;120:499509), is a unique attempt at trying to explain a new technology to a largely unversed audience. Unfortunately, a number of inaccuracies are contained in this article: 1. The statement that "methods currently available to assess the genotype allow only statistical information regarding a m a t c h " is incorrect. Developing D N A sequence information is possible and would be definitive because specific D N A sequences differ between any two individuals at approximately 0.1% of the D N A base sites. It is currently simply too cumbersome and costly to use sequencing routinely. 2. D N A is not constant in all tissues. Somatic mutation is well known to exist in lymphocyte development, and variation in chromosomal number has also been frequently detected. The exact extent of individual D N A variation is difficult to determine and is yet unknown. In addition, D N A patterns from identical twins need not be identical. In fact, Jeffreys has noted several sets of identical twins with different patterns using his techniques (personal communication). 3. Dr. M e C a b e states that "paternity cases are never resolved amicably." In m y experience, this is untrue. Resolution depends a great deal on how initial paternity counseling is delivered by medical geneticists and other counselors. 4. McCabe confuses the use of D N A technology in forensic settings. D N A analysis of evidence can never show that "the suspect is very likely to have been the assailant." Given current methods, it can only indicate a probability that a tested material has come from or not come from a population to which a suspect m a y or m a y not belong. "Assailants" are individuals who have been identified as perpetrating a crime. Genetics cannot be used for this sort of labeling. 5. According to M a r y C. King, who has been responsible for the development of D N A identification programs in Argentina, D N A typing has not as yet unified a single family in that country. 1 6. The use of D N A typing for immigration procedures (in Great Britain) and the storing of D N A by the armed services are significant extensions of medical genetics into social processes. M a n y knowledgeable scientists have raised important questions about these incursions and have pointed out the dubious history of the relationship of genetics to public process, including the horrendous history of eugenics in the United States. I believe Dr. M c C a b e should mention these facts as well.
Paul R. Billings, MD, PhD Department o f Medicine California Pacific Medical Center San Francisco, CA 94115 9/35/41174
REFERENCE 1. King MC. An application of D N A sequencing to a h u m a n rights problem. In: Friedman T, ed. Molecular genetic medicine. San Diego: Academic Press, 1991:117-31.
Reply To the Editor." Dr. Billings' response gives an opportunity to make several points that were considered during the development of the article. Material addressed by Dr. Billings was included in an early version of the manuscript but was deleted on the recommendation of colleagues who believed that such an approach was currently impractical in D N A forensics and therefore would be of little value to the readers of this article. Jeffreys et al. ~, 2 recognized at the outset of their work with hypervariable minisatellites that essential prerequisites for their use for purposes of identification would be that they "are stably inherited in a mendelian fashion, a n d . . , that these D N A fingerprints are also somatically stable," and they demonstrated these properties. These are highly variable polymorphisms; one would anticipate that the features of stability noted by Jeffreys et al. are relative, and, as noted in my article, 3 spontaneous mutations do occur in these tandem repetitive loci at a finite rate, which Jeffreys et al. observed at 0.006 per band per child. 4 Therefore, as I noted, 3 children will have bands differing from those of their parents, and these differences can be considered in calculations related to parentage. 5 It follows that, because somatic mutation is a well-recognized phenomenon, as noted by Dr. Billings, one m a y observe differences that occur after fertilization, including occasional variation between identical twins, as well as between D N A samples from cells and tissues within an individual. The rare occurrence of these events means that this type of variability will not be observed with high frequency, although when it is seen, as with band differences between identical twins, it is striking. 6 These rare somatic events do not affect the practical application of D N A forensics from the perspective of the practicing pediatrician. Two of Dr. Billings' comments seem to be in conflict. At one point he states that it is incorrect to assert that D N A identification atlows only statistical information to be obtained regarding a match; at another point, he maintains, "Given current methods, it [ D N A technology in forensic settings] can only indicate a probability that a tested material has come from or not come from a population to which a suspect m a y or m a y not belong." By all acceptable standards, current D N A technology m a y exclude an individual from identity, but inclusion can be shown only as a probability. In fact, much of the controversy concerning the use of D N A forensic evidence in the courts relates to the calculation of these probabilities. I agree with Dr. Billings that actual D N A sequence information
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Applications of DNA fingerprinting To the Editor: The recent article by McCabe, entitled "Applications of D N A Fingerprinting in Pediatric Practice" (J PEDIATR 1992;120:499509), is a unique attempt at trying to explain a new technology to a largely unversed audience. Unfortunately, a number of inaccuracies are contained in this article: 1. The statement that "methods currently available to assess the genotype allow only statistical information regarding a m a t c h " is incorrect. Developing D N A sequence information is possible and would be definitive because specific D N A sequences differ between any two individuals at approximately 0.1% of the D N A base sites. It is currently simply too cumbersome and costly to use sequencing routinely. 2. D N A is not constant in all tissues. Somatic mutation is well known to exist in lymphocyte development, and variation in chromosomal number has also been frequently detected. The exact extent of individual D N A variation is difficult to determine and is yet unknown. In addition, D N A patterns from identical twins need not be identical. In fact, Jeffreys has noted several sets of identical twins with different patterns using his techniques (personal communication). 3. Dr. M e C a b e states that "paternity cases are never resolved amicably." In m y experience, this is untrue. Resolution depends a great deal on how initial paternity counseling is delivered by medical geneticists and other counselors. 4. McCabe confuses the use of D N A technology in forensic settings. D N A analysis of evidence can never show that "the suspect is very likely to have been the assailant." Given current methods, it can only indicate a probability that a tested material has come from or not come from a population to which a suspect m a y or m a y not belong. "Assailants" are individuals who have been identified as perpetrating a crime. Genetics cannot be used for this sort of labeling. 5. According to M a r y C. King, who has been responsible for the development of D N A identification programs in Argentina, D N A typing has not as yet unified a single family in that country. 1 6. The use of D N A typing for immigration procedures (in Great Britain) and the storing of D N A by the armed services are significant extensions of medical genetics into social processes. M a n y knowledgeable scientists have raised important questions about these incursions and have pointed out the dubious history of the relationship of genetics to public process, including the horrendous history of eugenics in the United States. I believe Dr. M c C a b e should mention these facts as well.
Paul R. Billings, MD, PhD Department o f Medicine California Pacific Medical Center San Francisco, CA 94115 9/35/41174
REFERENCE 1. King MC. An application of D N A sequencing to a h u m a n rights problem. In: Friedman T, ed. Molecular genetic medicine. San Diego: Academic Press, 1991:117-31.
Reply To the Editor." Dr. Billings' response gives an opportunity to make several points that were considered during the development of the article. Material addressed by Dr. Billings was included in an early version of the manuscript but was deleted on the recommendation of colleagues who believed that such an approach was currently impractical in D N A forensics and therefore would be of little value to the readers of this article. Jeffreys et al. ~, 2 recognized at the outset of their work with hypervariable minisatellites that essential prerequisites for their use for purposes of identification would be that they "are stably inherited in a mendelian fashion, a n d . . , that these D N A fingerprints are also somatically stable," and they demonstrated these properties. These are highly variable polymorphisms; one would anticipate that the features of stability noted by Jeffreys et al. are relative, and, as noted in my article, 3 spontaneous mutations do occur in these tandem repetitive loci at a finite rate, which Jeffreys et al. observed at 0.006 per band per child. 4 Therefore, as I noted, 3 children will have bands differing from those of their parents, and these differences can be considered in calculations related to parentage. 5 It follows that, because somatic mutation is a well-recognized phenomenon, as noted by Dr. Billings, one m a y observe differences that occur after fertilization, including occasional variation between identical twins, as well as between D N A samples from cells and tissues within an individual. The rare occurrence of these events means that this type of variability will not be observed with high frequency, although when it is seen, as with band differences between identical twins, it is striking. 6 These rare somatic events do not affect the practical application of D N A forensics from the perspective of the practicing pediatrician. Two of Dr. Billings' comments seem to be in conflict. At one point he states that it is incorrect to assert that D N A identification atlows only statistical information to be obtained regarding a match; at another point, he maintains, "Given current methods, it [ D N A technology in forensic settings] can only indicate a probability that a tested material has come from or not come from a population to which a suspect m a y or m a y not belong." By all acceptable standards, current D N A technology m a y exclude an individual from identity, but inclusion can be shown only as a probability. In fact, much of the controversy concerning the use of D N A forensic evidence in the courts relates to the calculation of these probabilities. I agree with Dr. Billings that actual D N A sequence information
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