Etica científica de la terapia génica de individuos. Urgencia de la Cirugía Génica del ADN / Scientific ethics of gene therapy for individuals. The urgency for DNA gene surgery

Gene therapy for individuals is mainly directed to somatic or germ cells. The present technology aims to insert a DNA segment in the recipient cells. This therapy is useful in Mendelian recessive diseases. There is an ethical moratorium to perform insertion gene therapy in germ cells, because this procedure increases the human genome. Somatic cell gene therapy cures individuals but increases the gene frequency of genetic diseases in the population. This occurs because the descendants of the cured patient should carry his or her "ill" genes. We denots by "DNA gene surgery" the procedure that replaces "ill" nucleotide(s) by healthy one(s) conserving the genome size and the gene context of expression and regulation. Several procedures for gene surgery have been applied to cells and animals. Those based on DNA repair as Chimeric RNA/DNA, one stranded oligonucleotides and tristranded DNA. Those based on DNA recombination with oligo DNA or one stranded DNA, and transposable DNA segments. Gene surgery can be applied to germ cell gene therapy without ethical contraindications. It can cure Mendelian dominant diseases and it can be applied to heterozygotes. It preserves the regulation and expression gene context. If a technical safe procedure is available, the entire mankind could be treated and cured of all the Mendelian diseases, in one generation. Susceptibilities for all diseases could also be treated. The moratorium for research on germ cell gene therapy by gene surgery should be interrupted. Safe gene surgery is a moral imperative for gene therapy of patients and their descendants, for the treatment of dominant genetic diseases and for heterozygous carriers of recessive disorders.

Etica científica del aborto terapéutico / Scientific ethics of therapeutic abortion

Therapeutic abortion is proposed when a pregnancy threatens a woman's life and the fetus is not viable ex utero. As the intention is not to kill the fetus, this action should be named therapeutic interruption of pregnancy. However, in some cases the fetus directly hampers the mother's health. Thus, the removal of the cause of the disease coincides with killing the fetus. Therapeutic abortion has been proposed for several situations. A) When pregnancy and not the fetus, impairs maternal life (e.g. ovular infection, ectopic pregnancy, decompensation of a preexisting disease or diseases of pregnancy as pre-eclampsia/eclampsia, HELLP and Ballantyne syndromes, choriocarcinoma). B) A risk for maternal survival caused by the embryo or fetal genetic constitution: autoimmune diseases of the mother generated by fetal antigens, some types of eclampsia with or without HELLP syndrome due to an immune or exaggerated inflammatory response of the mother, Ballantyne syndrome associated to eclampsia due to fetal-maternal genetic incompatibility, the classic fetus-maternal genetic incompatibility, embryo or fetus diseases caused by their genomic constitution, mainly hydatidiform mole and the triploid, or fetal cancer. Scientific knowledge and a prudential Medical Ethics are capable to solve most cases.

Dimorfismo sexual en la pigmentación de la piel, color de ojos y pelo y presencia de pecas en adolescentes chilenos en dos estratos socioeconómicos / Sexual dimorphism in skin, eye and hair color and the presence of freckles in Chilean teenagers from two socioeconomic strata

BACKGROUND: The risk of skin cancer is correlated with skin colour. Pigmentation protects against the effects of UV radiation. AIM: To study skin, eyes and hair colour in Chilean teenagers. MATERIAL AND METHODS: The constitutive skin, hair and eyes colour and the presence of freckles was studied in 716 teenagers (416 females) of a low socio economical level and in 307 teenagers (155 females) of a high socio economical level. RESULTS: The proportion of foreign surnames was higher in the high stratum and we only found aboriginal surnames in the low stratum. The females of the lower stratum presented lighter skin than males. This difference was not observed in the higher stratum. We did not find significant differences in the eye colour between sexes, however, adolescents from the high stratum presented lighter eye colour. Females had lighter hair colour than males in both strata, also, we found lighter hair colour in the high stratum. We did not find significant differences in the presence of freckles between strata, but, the proportion of females with freckles was higher than that of males in both strata. CONCLUSIONS: Our results may identify different groups of people, within the Chilean population, with different susceptibility to the effects of ultraviolet radiation.

Misconceptions and false expectations in neutral evolution

Neutral evolution results from random recurrent mutation and genetic drift. A small part of random evolution, that which is related to protein or DNA polymorphisms, is the subject of the Neutral Theory of Evolution. One of the foundations of this theory is the demonstration that the mutation rate (m) is equal to the substitution rate. Since both rates are independent of population size, they are independent of drift, which is dependent upon population size. Neutralists have erroneously equated the substitution rate with the fixation rate, despite the fact that they are antithetical conceptions. The neutralists then applied the random walk stochastic model to justify alleles or bases that were fixated or eliminated. In this model, once the allele or base frequencies reach the monomorphic states (values of 1.0 or 0.0), the absorbing barriers, they can no longer return to the polymorphic state. This operates in a pure mathematical model. If recurrent mutation occurs (as in biotic real systems) fixation and elimination are impossible. A population of bacteria in which m = 10(-8) base mutation (or substitution)/site/generation and the reproduction rate is 1000 cell cycle/year should replace all its genome bases in approximately 100,000 years. The expected situation for all sites is polymorphism for the four bases rather than monomorphism at 1.0 or 0.0 frequencies. If fixation and elimination of a base for more than 500,000 years are impossible, then most of the neutral theory is untenable. A new complete neutral model, which allows for recurrent substitutions, is proposed here based on recurrent mutation or substitution and drift alone. The model fits a binomial or Poisson distribution and not a geometric one, as does neutral theory.

Idiopathic epilepsy with generalized tonic clonic seizures in Antioquia, Colombia: is the joint Amerindian and Negroid racial admixture the cause of its high prevalence?

Most Colombian populations stem from the admixture of Caucasians, Amerindians and Negroids. In the world, these two latter ethnical groups show a significantly higher prevalence of epilepsy than the former one. We tested the hypothesis that the high prevalence of idiopathic epilepsy with generalized tonic clonic seizures found in the Antioquian population (Paisas), from Colombia, is due to their possible joint Negroid and Amerindian ethnic components. We have previously demonstrated that inheritance is the principal factor for developing epilepsy in this community. Analyses of racial admixture, heterogeneity between populations, genetic distance, and phyletic relationships were performed among epileptic and non epileptic samples from the Antioquian community. Also Caucasians, Spaniards, Basques, Jews, Chileans, Negroids, Amerindians and Mongoloids were included in the analysis. Four highly polymorphic blood systems were used as genetic markers: RH, MNS, ABO and FY. They were chosen because of their high discriminant power in these ethnic groups. In the population affected with idiopathic epilepsy, the estimated Negroid and Amerindian rates of admixture were low (3 percent and 14 percent, respectively). Although, these degrees of admixture can be explained due to common ancestral origins, the estimated proportion of Amerindian admixture in the epileptic affected population, was significantly higher than the estimated for the Non affected Antioquian population. The latter finding is consistent with the analysis of heterogeneity between populations that discriminated epileptic population from non epileptic Antioquian population (p < 0.05). Epileptic and non epileptic Paisas clustered in topology with Caucasians, very close to Spaniards and Basques and highly distant from Negroids and Amerindians. Thus, far, the origin of the high prevalence of idiopathic epilepsy in the Antioquian (Paisa) population cannot be explained by the hypothetical joint Negroid and Amerindian ethnical admixture, but using additional genetic markers and other methods of racial estimation of admixture it is necessary to corroborate if the Amerindian admixture component is significantly higher in the epileptic population than in the non epileptic Paisa population

A model of complete random molecular evolution by recurrent mutation

A model for random molecular evolution based on recurrent mutation is proposed. Recurrent mutation replaces completely any original base in a nucleotidic site. This occurs if more than four times the number of reproductive cycles equal to the reciprocal of the mutation rate happen; no matter the population size, the number of nucleotides a genome has, or the taxa at which it belongs. The main results are: i) the expected distribution of DNA bases in a site is an isotetranomial distribution, where Adenine (A), Guanine (G), Cytosine (C) and Thymine (T) occur with probability equal to 0.25; ii) the distribution of bases in a site is independent from the distribution of bases in other sites. Several expected consequences that can be contrasted with actual data are generated. Species or operational taxonomic units (OTUs) that evolved in big populations should present distances equal to zero and similarities equal to one. OTUs evolving in small populations should present distances equal to 3/4 and similarities equal to 1/4. Thus, random molecular evolution by recurrent mutation cannot yield a tree at all. The only possible tree is that produced by random fluctuations of distances according to their variances (stochastic tree). Some consequences of the model on the expected primary structure of proteins are also analyzed. There are sufficient generations for any DNA segment evolving apart during the last four hundred million years, to reach those expected base distributions

New evidence of non seasonal factors in the menarche rhythm

The phylogenetic, ontogenetic and seasonal hypotheses on the annual periodicity of menarche were tested. Data from European, Asian (Caucasian, Mongolian and Caucaso-Mongolian people from the northern hemisphere) and Chilean (Caucaso-Amerindian from the southern hemisphere) populations were compared with data from Hungary (Caucaso-Mongolian Europeans from a northern temperature zone) and Madras, India (a complex ethnically originated people from a tropical northern area). Chileans were compared with those Caucaso-Mongolian people because Amerindians belong also to the Mongolian group. Hungarian girls showed peaks of menarche in the month of January (winter), June, July and August (summer), in contradiction with most European Caucasians who showed peaks only in winter months; and in agreement with Finns who showed both peaks. Indian girls had peaks in April, May and June (summer) and more extreme peaks and troughs than the Finnish girls (from a temperature arctic zone). These findings do not agree with the seasonal hypothesis, but they do with the phylogenetic hypothesis. Indian girls had a peak of menarche in the same month of birth and the arrangement of data according to the gestational-menarche coincidence showed a significant heterogeneity for the monthly peaks of menarche; thus, the ontogenetic hypothesis was also supported

Analisis del grupo sanguineo Rh en fratrias. Un nuevo sistema de histocompatibilidad en el hombre?. / Analysis of the Rh blood group in brothers. A new histocompatibility system in men?

Se examina el sistema sanguineo Rh en una muestra de ninos del Area Norte de Santiago.Los antisueros utilizados fueron: antiC, antic, antiD, antiE y antie. 73 parejas de hermanos quedaron incluidas en la muestra, los hermanos no tienen mas de tres anos de diferencia en edad que sus respectivos casos indices. Los casos indices presentaron frecuencias superiores de RH3(CDe/CDe) e inferiores de RH5(CDe/cDE) y RH6(CDe/cde) que las encontradas en la muestra de hermanos. De l7 parejas de hermanos donde los indices pertenecian al grupo RH3, solo un hermano tuvo ese mismo fenotipo,el resto se distribuyo en: RH5, RH6, RH7(cDE/cDE, 1) y Rh18 (cde/cde, 1). La probabilidad de produccion al azar de este resultado es P<0.00002. Para explicar estos resultados, postulamos que hay un sistema mayor de histocompatibilidad asociado al sistema Rh en el cromosoma 1 humano

Estudio bayesiano del rendimiento escolar segun diez pruebas neurologicas. / Bayesian study of school performance according to 10 neurological tests

Existe un interes creciente en predecir las dificultades que un nino tendra en la escuela sabiendo su rendimiento en pruebas neurologicas. Hemos calculado, conocidas las frecuencias de rendimiento en 10 pruebas neurologicas de ninos clasificados segun rendimiento escolar, las probabilidades de rendimiento escolar dado un resultado en estas 10 pruebas neurologicas, aplicando la inversion Bayesiana de probabilidades condicionales