The Chilean socio-ethno-genomic cline.

Studies of the current Chilean population performed using classical genetic markers have established that the Chilean population originated primarily from the admixture of European people, particularly Spaniards, and Amerindians. A socioeconomic-ethno-genetic cline was established soon after the conquest. Spaniards born in Spain or Chile occupied the highest Socioeconomic Strata, while Amerindians belonged to the lowest. The intermediate strata consisted of people with different degrees of ethnic admixture; the larger the European admixture, the higher the Socioeconomic Level. The present study of molecular genomic markers sought to calculate the percentage of Amerindian admixture and revealed a finer distribution of this cline, as well as differences between two Amerindian groups: Aymara and Mapuche. The use of two socioeconomic classifications - Class and Socioeconomic Level - reveals important differences. Furthermore, Self-reported Ethnicity (self-assignment to an ethnic group) and Self-reported Ancestry (self-recognition of Amerindian ancestors) show variations and differing relationships between socioeconomic classifications and genomic Amerindian Admixture. These data constitute a valuable input for the formulation of public healthcare policy and show that the notions of Ethnicity, Socioeconomic Strata and Class should always be a consideration in policy development.

Quantitative interactions between Candida albicans and the mutans streptococci in patients with Down Syndrome.

BACKGROUND: Oral microorganisms produce damage through the transfer to bloodstream, colonizing other tissues or direct damage in the oral cavity. Aim to study the quantitative interactions between C. albicans and the mutans streptococci and ms serotypes in the saliva of the oral cavity of patients with Down syndrome (DS). MATERIAL AND METHODS: Included 120 patients of both genders, 60 patients with Down syndrome (DS) and 60 pa- tients as a control group (CG). Samples of saliva were taken, and bacteria and fungi were grown on TYCSB and Saboureaud agar. Microbiological, serological and quantitative analyses were performed to determine the kind of isolated of microorganisms corresponding to the ms c, e, f and k for species S. mutans and d and g for S. sobrinus and C. albicans. Electronic scanning microscopy was employed to visualize and confirm the colonies under study. Statistics analysis included t-test proofs for matched data test, Scheffé and ANOVA. RESULTS: Forming units (CFU) per mL of saliva of C. albicans a significant difference was observed among DS

Malignant melanoma in Chile: an unusual distribution of primary sites in men from low socioeconomic strata.

BACKGROUND: Mortality from malignant melanoma (MM) has increased in Chile in the past decade. The location of MM lesions on the body has been correlated with prognosis and survival. AIM: To review body site and gender relationships with histopathologically confirmed primary MM in Chile. METHODS: Records of 575 cases presenting to 5 state hospitals from 1992 to 2001 were analysed. RESULTS: There were 360 women and 215 men. Women showed a significantly higher number of MM on the legs, cheeks and arms, and in the genital area, whereas men showed a significantly higher number on the ears, backs of the hands, soles and feet. Men had a predilection for MM with a poor prognosis. CONCLUSION: The different body site distribution of primary MM in men and women may be explained by a different pattern of sun exposure. Ethnic and genetic factors may also be involved. The predominant location of MM in women in Chile is similar to white populations, whereas the location in men is similar to that observed in black and Asian populations. These observations may be relevant to the high mortality of MM in Chilean men.

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.

Human Raphe Magnus Nucleus: a morphometric Golgi-Cox study with emphasis on sex differences.

The number and proportion of neurons according to their type and size in the Raphe Magnus Nucleus stained by the Golgi-Cox and Nissl methods were compared in male and female infants. Four female/male pairs aged from 2 to 150 days were studied. While females showed more neurons than males, males showed a higher proportion of large multipolar (more than 40 microm) and fusiform neurons (more than 20 microm) but not of ovoid neurons (more than 15 microm). These differences varied according to the type of cells and age of infants. Some of these results are similar to those found in the human Median Raphe Nucleus with the same methods.

[Scientific ethics and frozen embryos]. / Etica científica y embriones congelados.

BACKGROUND: Scientific Ethics is the theory and praxis of decisions. Philosophical Ethics is presented as the theory and praxis of the good. As the good differs among cultures, Philosophical Ethics is dependent on the endo-cultural good conception. The decision (included that one of adhesion or not to a world vision) depends on neuro-psychic specific factors: i) cognitive factors that include mostly the knowledge of the alternatives and their consequences and the ideological or religious conception of good in relation to the alternatives; ii) affective factors that make alternatives pleasant, unpleasant or neutral, attractive, repulsive or neutral; iii) emotional factors that associate to alternatives anger, peace or neutrality, sadness, happiness or neutrality; iv) value factors that assign importance, triviality or neutrality to alternatives, or assign them significance, irrelevancy or neutrality. There are unspecific factors such as the psychic energy, desire or others. Mixed factors such as attitude, motivation, intention and others. Scientific Ethics deals with the mind as a materio-energetic process which is different from the soul, eggs and embryos of any species are full individuals of that species, because, they have initiated a copy of their genome that specify, give autonomy and define them as individuals. For Scientific Ethics to leave frozen embryos like that for ever, to defrost and get rid of them or to use their cells for science are synonymous of killing them. To defrost them to use their cells as stem cells for somatic cell therapy or to implant them into uteri to continue their development is to maintain alive their cells, but only the implantation allows their maintenance as individuals, thus, being the only compatible with the Christian ethics. The compatibility of these alternatives with other ethics is discussed.

[Ontogenetic origin of the human individual from his genome]. / Comienzo ontogénico del individuo humano desde su genoma.

Diverse propositions about the ontogenetic origin of a live organism, specially human beings, are examined. Unambiguous and objective propositions about this origin are that a live organism is an ontogenetically programmed and integrated organisation, that the origin condition has the greater influence on other processes, that in pluricellular organisms, no organ or tissue can be considered critical to establish origins and that the origin must be established by endogenous elements. Several hypotheses about the origin of life are discarded. The integration between oocyte cytoplasm and the genetic material that it receives, that culminates in the first genome replication, is proposed as the process that gives origin to the individual. This process occurs in all living organisms.

Sexual dimorphism in number and proportion of neurons in the human median raphe nucleus.

The number and proportion of neurons in the median raphe nuclei stained by the Golgy-Cox and Nissl methods was compared in males and females infants. When subjects are matched by age and cause of death the number and proportion of fusiform, ovoid and multipolar cells differs significantly between sexes at different ages.

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.

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.

[Annual school and menarche rhythms (vacation-study)]. / Ritmos anuales escolar (vacaciones-estudio) y de menarquia.

BACKGROUND: It has been hypothesized that the yearly menarche rhythm could be caused by the seasonal variation of photoperiod and temperature or by the annual distribution of the scholar vacation and study periods. AIM: To test the hypothesis that the distribution of study vacation periods is a condition that modifies the annual menarche rhythm. SUBJECTS AND METHODS: Two thousand ninety four school girls from Chile, 2,356 girls from Madras, India, 3,454 girls from Medellin, Colombia and 2,627 girls from Debrecen, Hungary, were studied. They were asked about the month of their menarche. Vacation months were considered those with more than 6 days of leave from school. RESULTS: The seasonal hypothesis was refuted because there were contradictions with the expected antithetical behavior in both hemispheres, there was a significant heterogeneity of the yearly menarche among girls from the same region, the expected cline of the menarche frequency variance from equator to poles was not observed, finding an antithetical cline instead and there was a significant heterogeneity among months of the same season. On the other hand, months with vacation periods coincided significantly with peaks of menarche, while study months had lower proportion of menarche (total binomial probability < 10(-6)). Girls whose month of menarche was the same as their month of birth, did not agree completely with the vacation-study hypothesis as the rest of the sample. CONCLUSIONS: Vacation periods influenced menarche rhythm. However, these periods coincide with most cultural events and this strong association needs further study to be considered causal. It is not possible to assume school stress as the main explanatory variable. Ontogenetic factors such as birth imprinting also can influence the menarche rhythm, as shown in girls whose month of menarche coincided with their month of birth.

[Sexual dimorphism in human medial raphe nuclei. Preliminary study with the Golgi cox method]. / Dimorfismo sexual en el núcleo mediano del rafe humano. Estudio preliminar con el método de Golgi cox.

Brains from a female and a male newborn who died from an asphictic syndrome were examined to study the cytoarchitecture of the median raphe nucleus using the Golgi-Cox and morphometric methods. This nucleus is part of the serotonergic system. The morphometric analysis showed in the female newborn a significant increase of neurons. Also she had a higher proportion of ovoid and multipolar cells and a lower proportion of fusiform cells than the newborn male. Our findings suggest that this neuronal distribution may be the anatomical substrate for a serotonergic specific system in each sex.

Distribution of (CGG)n and FMR-1 associated microsatellite alleles in a normal Chilean population.

We report on the allele distribution in a normal Chilean population at 2 microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5' end of the FMR-1 gene, which causes the fragile X syndrome. The most common CGG repeat allele was 30 (41.7%), with 29 being second most common (30.2%). This distribution was similar from that seen in Caucasians but different from that observed in Chinese controls, where the most common allele was 29 repeats. Four alleles of FRAXAC1 and 6 of DXS548 were observed in the Chilean sample. A striking linkage disequilibrium of FMR-1 alleles with FRAXAC1 alleles was observed. In 90% of the 30 CGG repeat alleles only 31% of the 29 CGG repeat alleles had the FRAXAC1 154 bp allele. This result is in agreement with the suggestion that slippage between CGG repeat alleles 29 and 30 and between 152 and 154 FRAXAC1 alleles is very rare. This study suggests a founder chromosome effect in the Chilean population.

Intelligence and genetic markers in Chilean children.

Genetic markers and total intelligence quotient (IQ) assessed by WISC (Wechsler Intelligence Scale for Children) were studied in children of both sexes from Santiago, Chile. Heterozygous boys for phosphoglucomutase 1 (PGM) and heterozygous girls for haptoglobin (Hp) had lower IQ than homozygotes. For ABO system, B girls had lower and B boys had higher IQ than children with other ABO phenotypes. These differences were highly significant with the two tailed t'-test (Student's t-test with the Welch-Satterthwaite correction for degrees of freedom), and most of them remained significant after the correction for multiple comparisons. Girls had greater variance of IQ than boys. Relationships between homozygotes and heterozygotes were found in two independent studies. Thus, the genetic relationship found here seems likely to be a true biotic effect.

[Scientific ethics of the origin of humans]. / Etica científica del origen humano.

The analysis of the early human life from the view point of a scientific ethics is presented. Life is a historical materioenergetic process of specific organization. This phylo-ontogenetic process is a continuous process without interruption. Biology has demonstrated that human eggs or embryos are full human individuals, even though not all human conception is a human being. The contradictions involved in taking ethical decisions after knowing the percentage of conceptions obtained by in vitro or in fallopian tube fertilization that reach the birth are shown. The advantages of scientific ethics in the analysis of the origin of the different positions are indicated. These advantages come from the dissection of the different cognitive, affective-emotional and value attribution frames involved in the alternative decisions.