reply to geoffrey a machin

1
Letter to the Editor Reply to Geoffrey A. Machin To the Editor: We agree with Dr. Machin’s comments regarding the desirability of studying DNA from parents and auto- site, in addition to the parasite, but it was not possible; we emphasized this limitation in our paper [Logrono et al., 1997]. However, we felt that it was important to introduce the possibility of fusion of two embryos as a mechanism for conjoint twinning in the rare situation where the axis of the twins is perpendicular rather than parallel, since a parallel orientation would be ex- pected if the malformation were due to incomplete fis- sion of a single zygote. Because polarity in the embryo is established very early, we sought evidence of fusion in other mammals and, therefore, used the horse as an example. Unlike other ungulates with epitheliochorial placentation, horses do not have the intimate associa- tion between twin embryos that enables development of freemartin cattle [Jainudeen and Hafez, 1993]. The criticism that artifacts in DNA analysis could have led to misinterpretation is sometimes used in murder trials to dispute DNA evidence, and this can never be completely ruled out relative to any single locus. However, because we are comparing STRs rather than VNTRs, there is less likelihood of artifactual breakdown during processing. Although there may be a high postzygotic mutation rate of STRs, it is significant that we found four of six to be consistent with dizygos- ity, which satisfies the criterion of Martin et al. that dizygosity should not be diagnosed until two STR dif- ferences between co-twins have been found [Martin et al., 1997]. Since the error leading to fusion in our case had to have occurred shortly after implantation of the autosite and before development of the chorionic sac, there is no need to explain disruption of the diamniotic dichorionic septum. Although it would have been desirable to ex- amine the placental chorionic status at delivery, this was not possible because the obstetrician considered the placenta to be normal and, therefore, discarded it, which suggests that the placenta was unremarkable. We appreciate Dr. Machin’s comments and wish that it would have been possible to do the kind of studies that he suggested. However, based on the limited ma- terial that was available to us, we think that we have made a reasonable case for embryonic fusion as a mechanism for conjoint twinning in cases where the alignment of the twins is more perpendicular than par- allel. REFERENCES Jainudeen MR, Hafez ESE (1993): Gestation, prenatal physiology, and parturition. Genetics of reproductive failure. In: Hafez ESE (Ed): “Re- production in Farm Animals.” 6th ed. Philadelphia: Lea & Febiger, pp 213–236, 298–311. Logrono R, Garcia-Lithgow C, Harris C, Kent M, Meisner L (1997): Het- eropagus conjoined twins due to fusion of two embryos: Report and review. Am J Med Genet 73:239–243. Martin N, Boomsa D, Machin G (1997): A twin-pronged attack on complex traits. Nat Genet 17:387–392. Roberto Logrono Charles Harris Marijo Kent Lorraine Meisner* State Laboratory of Hygiene University of Wisconsin Madison, Wisconsin *Correspondence to: Dr. Lorraine Meisner, Cytogenetics Sec- tion, State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706. Received 13 January 1998; Accepted 20 February 1998 American Journal of Medical Genetics 78:390 (1998) © 1998 Wiley-Liss, Inc.

Upload: lorraine

Post on 06-Jun-2016

214 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Reply to Geoffrey A Machin

Letter to the Editor

Reply to Geoffrey A. Machin

To the Editor:

We agree with Dr. Machin’s comments regarding thedesirability of studying DNA from parents and auto-site, in addition to the parasite, but it was not possible;we emphasized this limitation in our paper [Logrono etal., 1997]. However, we felt that it was important tointroduce the possibility of fusion of two embryos as amechanism for conjoint twinning in the rare situationwhere the axis of the twins is perpendicular ratherthan parallel, since a parallel orientation would be ex-pected if the malformation were due to incomplete fis-sion of a single zygote. Because polarity in the embryois established very early, we sought evidence of fusionin other mammals and, therefore, used the horse as anexample. Unlike other ungulates with epitheliochorialplacentation, horses do not have the intimate associa-tion between twin embryos that enables developmentof freemartin cattle [Jainudeen and Hafez, 1993].

The criticism that artifacts in DNA analysis couldhave led to misinterpretation is sometimes used inmurder trials to dispute DNA evidence, and this cannever be completely ruled out relative to any singlelocus. However, because we are comparing STRs ratherthan VNTRs, there is less likelihood of artifactualbreakdown during processing. Although there may be ahigh postzygotic mutation rate of STRs, it is significantthat we found four of six to be consistent with dizygos-ity, which satisfies the criterion of Martin et al. thatdizygosity should not be diagnosed until two STR dif-ferences between co-twins have been found [Martin etal., 1997].

Since the error leading to fusion in our case had tohave occurred shortly after implantation of the autosite

and before development of the chorionic sac, there is noneed to explain disruption of the diamniotic dichorionicseptum. Although it would have been desirable to ex-amine the placental chorionic status at delivery, thiswas not possible because the obstetrician consideredthe placenta to be normal and, therefore, discarded it,which suggests that the placenta was unremarkable.

We appreciate Dr. Machin’s comments and wish thatit would have been possible to do the kind of studiesthat he suggested. However, based on the limited ma-terial that was available to us, we think that we havemade a reasonable case for embryonic fusion as amechanism for conjoint twinning in cases where thealignment of the twins is more perpendicular than par-allel.

REFERENCESJainudeen MR, Hafez ESE (1993): Gestation, prenatal physiology, and

parturition. Genetics of reproductive failure. In: Hafez ESE (Ed): “Re-production in Farm Animals.” 6th ed. Philadelphia: Lea & Febiger, pp213–236, 298–311.

Logrono R, Garcia-Lithgow C, Harris C, Kent M, Meisner L (1997): Het-eropagus conjoined twins due to fusion of two embryos: Report andreview. Am J Med Genet 73:239–243.

Martin N, Boomsa D, Machin G (1997): A twin-pronged attack on complextraits. Nat Genet 17:387–392.

Roberto LogronoCharles HarrisMarijo KentLorraine Meisner*State Laboratory of HygieneUniversity of WisconsinMadison, Wisconsin

*Correspondence to: Dr. Lorraine Meisner, Cytogenetics Sec-tion, State Laboratory of Hygiene, 465 Henry Mall, Madison, WI53706.

Received 13 January 1998; Accepted 20 February 1998

American Journal of Medical Genetics 78:390 (1998)

© 1998 Wiley-Liss, Inc.