Heterogeneity coordinates bacterial multi-gene expression in single cells.

For a genetically identical microbial population, multi-gene expression in various environments requires effective allocation of limited resources and precise control of heterogeneity among individual cells. However, it is unclear how resource allocation and cell-to-cell variation jointly shape the overall performance. Here we demonstrate a Simpson's paradox during overexpression of multiple genes: two competing proteins in single cells correlated positively for every induction condition, but the overall correlation was negative. Yet this phenomenon was not observed between two competing mRNAs in single cells. Our analytical framework shows that the phenomenon arises from competition for translational resource, with the correlation modulated by both mRNA and ribosome variability. Thus, heterogeneity plays a key role in single-cell multi-gene expression and provides the population with an evolutionary advantage, as demonstrated in this study.

Association of Ancestral Genetic Admixture and Excess Weight at Twelve Months of Age.

Background/Objective: Understanding the influence of genetically determined ancestry may give insight into the disparities of obesity seen in different ethnic groups beginning at a very early age. Aim: To investigate the relationship between children's ancestral genetic proportions and excess weight at 12 months of age. Methods: Eight hundred twenty-one 12-month-old children were included in this cross-sectional study. Their genetic admixture was estimated using the ancestry and kinship tool kit by projecting the samples into the 1000 Genomes principal component database. Weight-for-length percentile (WFLP) at 12 months of age was categorized as <95th percentile or ≥95th percentile. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association of admixture proportions, including European (EUR), admixed American (AMR), African (AFR), South Asian (SAS), and East Asian (EAS) populations, with WFLP categories, adjusting for maternal education, birth weight, frequency of breastfeeding, and juice consumption. Results: Eight hundred twenty-one children were included; WFLP <95th percentile = 671 (81.7%) and WFLP ≥95th percentile = 150 (18.3%). Crude ORs showed that the EUR admixture was protective [OR 0.45 (95% CI 0.27-0.74)], whereas AMR [OR 3.85 (95% CI 1.92-7.70)] and AFR [OR 5.70 (95% CI 2.19-14.85)] admixtures were positively associated with excess weight. After adjusting for confounding variables, only the AFR admixture was associated with WFLP ≥95th percentile [OR 7.38 (95% CI 2.31-23.59)]. Conclusions: AFRs remain associated with early excess weight after accounting for confounding variables, suggesting that this ancestral genetic background may contribute to the differences seen in early childhood obesity.

Further evidence of a left hemisphere specialization and genetic basis for tool use skill in chimpanzees (Pan troglodytes): Reproducibility in two genetically isolated populations of apes.

It has been hypothesized that the evolution of tool use may have served as a preadaptation for the emergence of left hemispheric specialization in motor skill in humans. Here, we tested for intermanual differences in performance on a tool use task in a sample of 206 captive chimpanzees in relation to their sex, age, and hand preference. In addition, we examined heritability in tool use skill for the entire sample, as well as within 2 genetically isolated populations of captive chimpanzees. This was done to determine the degree of reproducibility in heritability on motor performance. The results revealed a significant effect of hand preference on intermanual differences in performance. Right-handed chimpanzees performed the task more quickly with their right compared with left hand. In contrast, no significant intermanual differences in performance were found in left- and ambiguous-handed apes. Tool use performance was found to be significantly heritable for overall performance, as well as separately for the left and right hands. Further, significant heritability in tool use performance was found in both populations of apes, suggesting these results were reproducible. The results are discussed in the context of evolutionary theories of handedness and hemispheric specialization and the genetic mechanisms that underlie their expression in primates, including humans. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Causality in Biological Transmission: Forces and Energies.

Transmission is a basic process in biology that can be analyzed in accordance with information theory. A sender or transmitter located in a particular patch of space is the source of the transmitted object, the message. A receiver patch interacts to receive the message. The "messages" that are transmitted between patches (eventually located in different hierarchical biological levels) are "meaningful" biological entities (biosemiotics). cis-acting transmission occurs when unenclosed patches acting as emitter and receiver entities of the same hierarchical level are linked (frequently by a vehicle) across an unfit space; trans-acting transmission occurs between biological individuals of different hierarchical levels, embedded within a close external common limit. To understand the causal frame of transmission events, we analyze the ultimate, but most importantly also the proximate, causes of transmission. These include the repelling, centrifugal "forces" influencing the transmission (emigration) and the attractive, centripetal "energies" involved in the reception (immigration). As transmission is a key process in evolution, creating both genetic-embedded complexity-diversity (trans-acting transmission, as introgression), and exposure to novel and alternative patches-environments (cis-acting transmission, as migration), the causal frame of transmission shows the cis-evolutionary and trans-evolutionary dimensions of evolution.

Transtorno do espectro autista: onde estamos e para onde vamos / Autism spectrum disorders: where we are and where we are going / Trastorno de espectro autista: dónde estamos y hacia dónde vamos

A ampliação do conhecimento científico sobre o autismo pode ser identificado pelo aumento na produção de pesquisas sobre este transtorno nas últimas décadas, implicando atualizações recentes em sua classificação, compreensão e intervenção. O objetivo deste artigo é apresentar uma revisão da literatura sobre o autismo, apontando como os avanços investigativos recentes têm lançado luz sobre a compreensão do transtorno. Relata historicamente como os critérios para o diagnóstico nos manuais médicos de classificação foram aprimorados, complementados e suplantados com base em evidências até o atual DSM-5. É realizada uma revisão das contribuições teóricas e empíricas que impulsionaram essas mudanças para sintetizar o que tem sido considerado como aspectos centrais desse transtorno como espectro dimensional. Problematiza o aumento do número de diagnósticos a partir dos dados epidemiológicos atuais, destacando o que as pesquisas multidisciplinares têm identificado como fatores etiológicos e prognósticos para a vida adulta. Por fim, revisa brevemente o panorama dos principais programas e modelos de intervenção baseados em evidências para pessoas com autismo nas áreas da saúde e educação, para então apontar os atuais desafios neste contexto.

The diffusion of scientific knowledge about autism can be explained trough the increasing number of researches on this disorder in the last decades, implying in recent updates in its classification, understanding and intervention. The purpose of this paper is to present a literature review on autism highlighting how the recent investigative advances that have shed light on the understanding ofthe disorder. It reports historically how the first diagnostic criteria were being improved, supplemented and supplanted in the medical classification manuals, based on research until DSM-5. A review of empirical researches that drove these changes is performed to synthesize what has been considered as core aspects of this disorder as a dimensional spectrum. Discusses the increasing number of diagnoses, emphasizing the points that the multidisciplinary research has identified as possible causes, and the knowledge about the development expectations for adulthood. Finally, it reviews the landscape of the main programs and intervention models for people with autism in health and education fields, to point out to the current challenges and those to be addressedin the future

El propósito de este artículo es presentar una revisión de la literatura sobre el autismo señalando los avances recientes de investigación resultantes que han arrojado luz sobre la comprensión del trastorno. Informa históricamente como los criterios para este diagnóstico en la clasificación de los manuales de medicina se están siendo avanzados, complementados y suplantados con base en la investigación por la corriente del DSM-5. Se realiza una revisión de las investigaciones empíricas que impulsó a estos cambios para sintetizar lo que se ha considerado como aspectos centrales de este trastorno como un espectro dimensional. Se analiza el creciente número de diagnósticos, enfatizando o que las investigaciones multidisciplinares han identificado como posibles causas, y lo que se sabe acerca de las expectativas de desarrollo para la edad adulta. Por último, revisa el panorama de los principales programas y modelos de intervención para las personas con autismo en las áreas de salud y educación, para apuntar a los retos actuales en este contexto y aquellos que se abordarán en el futuro.

Estimação de valores genéticos para codornas europeias em função dos níveis da relação treonina: lisina da dieta: do nascimento aos 21 dias de idade / Estimation of breeding values for European quails in function of threonine: lysine ratios of diet: from birth to 21 days of age

O presente trabalho foi realizado com o objetivo de avaliar a sensibilidade dos valores genéticos dos pesos corporais e as características de carcaças de codornas europeias às mudanças do gradiente ambiental (níveis da relação treonina com a lisina das dietas), do nascimento aos 21 dias de idade, por meio de modelos de regressão aleatória com diferentes classes de variância residual. Os dados utilizados neste estudo são provenientes de 915 codornas de corte da linhagem LF1 e 839 da linhagem LF2, pertencentes ao Programa de Melhoramento Genético da Universidade Federal dos Vales do Jequitinhonha e Mucuri. Foram avaliados os pesos corporais e os rendimentos da carcaça das aves. As sensibilidades dos valores genéticos às mudanças nos níveis da relação treonina:lisina (interação genótipo x ambiente) foram obtidas por modelos de regressão aleatória (utilizando normas de reação) por meio do programa Wombat, que utiliza o princípio da máxima verossimilhança restrita (REML). O modelo de regressão aleatória que considerou duas classes de variância residual foi o mais indicado para a maioria das análises realizadas. Verificaram-se alterações na classificação dos valores genéticos para as duas linhagens de codornas de corte estudadas. Esse comportamento indica sensibilidade de valores genéticos aditivos às mudanças nutricionais, o que caracteriza a existência de interação genótipo x ambiente. A predição dos valores genéticos deve ser feita com o mesmo nível da relação treonina:lisina da dieta com a qual as codornas serão alimentadas no sistema de produção.(AU)

This research was carried out to evaluate the sensitivity of breeding values of body weight and carcass traits in two lines of European quails (LF1 and LF2) to changes in the environment gradient (levels of threonine: lysine ratio of diets) from hatch to 21 days of age in two lines LF1 and LF2 using Random Regression Models with different classes of residual variance. Records are from 915 quails of line LF1 and 839 of line LF2 belonging to the Breeding Improvement Program of Universidade Federal dos Vales do Jequitinhonha e Mucuri. Live body weight and weights and yields of carcass, breast, and thigh and drumstick were measured. The sensitivities of breeding values to changes in threonine: lysine ratios (genotype x environment interaction) of diets were obtained by random regression models (reaction model) using the WOMBAT program using the Restricted Maximum Likelihood principle. Model considering two classes of residual variance showed the best goodness of fit. The Reaction Norms analyses indicated changes in the ranking of breeding values for both lines suggesting quails selected in one level of threonine: lysine ratio will not express all their genetic potential if fed different threonine: lysine ratio diets. This behavior indicates sensitivity of breeding values to changes in the nutrition characterizing the genotype by environment interaction. The prediction of breeding values must be performed using the same level of threonine: lysine ratio in diet the quails will be fed in the production system.(AU)

Heritability of the network architecture of intrinsic brain functional connectivity.

The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23 ± 2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h(2) (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤ 15%), and when global signal regression was implemented, heritability estimates decreased substantially h(2) (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.

Genomic editing tools to model human diseases with isogenic pluripotent stem cells.

Patient-specific induced pluripotent stem cells (iPSCs) are considered a versatile resource in the field of biomedicine. As iPSCs are generated on an individual basis, iPSCs may be the optimal cellular material to use for disease modeling, drug discovery, and the development of patient-specific cellular therapies. Recently, to gain an in-depth understanding of human pathologies, patient-specific iPSCs have been used to model human diseases with some iPSC-derived cells recapitulating pathological phenotypes in vitro. However, complex multigenic diseases generally have not resulted in concise conclusions regarding the underlying mechanisms of disease, in large part due to genetic variations between disease-state and control iPSCs. To circumvent this, the use of genomic editing tools to generate perfect isogenic controls is gaining momentum. To date, DNA binding domain-based zinc finger nucleases and transcription activator-like effector nucleases have been utilized to create genetically defined conditions in patient-specific iPSCs, with some examples leading to the successful identification of novel mechanisms of disease. As the feasibility and utility of genomic editing tools in iPSCs improve, along with the introduction of the clustered regularly interspaced short palindromic repeat system, understanding the features and limitations of genomic editing tools and their applications to iPSC technology is critical to expending the field of human disease modeling.

[RTEL1 (regulator of telomere elongation helicase 1), a DNA helicase essential for genome stability]. / RTEL1, une hélicase de l'ADN essentielle à la stabilité du génome.

RTEL1 (regulator of telomere length helicase 1) is a DNA helicase that has been identified more than 10 years ago. Many works since, mainly in the nematode Caenorhabditis elegans and the mouse, have highlighted its role in chromosomal stability, maintenance of telomere length, and DNA repair. Recently, four laboratories have characterized RTEL1 mutations in patients with dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson (HH) syndrome, a rare and severe variant of DC. We here summarize the current knowledge on RTEL1 and discuss the possible other functions that RTEL1 could play.

Phenocopies in families with essential tremor and restless legs syndrome challenge Mendelian laws. Epigenetics might provide answers.

Essential Tremor (ET) and Restless Legs Syndrome (RLS) are both highly heritable neurological disorders. The frequent occurrence of multi-incident families suggests the existence of highly penetrant alleles. However, linkage analyses and positional cloning approaches performed within the last 10 years essentially failed to identify responsible mutations. Several loci were found, but their relevance was questioned given the occurrence of suspected phenocopies in many of those families. Remarkably, in some ET and RLS families with an apparent autosomal dominant mode of transmission, the proportion of affected individuals was higher than the expected 50% and therefore suggests a non-mendelian inheritance in some cases. In fact, there is increasing evidence that epigenetic modifications, which refer to changes in gene expression without changes in DNA sequence, can be transmitted to the next generation. Moreover, epigenetic information can be transferred from one allele of a gene to the other allele of the same gene; if then inherited to the next generation, the offspring consequently presents phenotypic properties related to the untransmitted allele. This phenomenon known as paramutation is well documented in plants and has recently been shown to occur also in mammals. Here, I explore the possibility that it is the epigenetic and not only the genetic state which confers disease risk in families. Inheritance of epigenetic mutations along with paramutational events have the potential to explain the non-mendelian features in the genetics of both diseases.

Phylogeny of Mycobacterium tuberculosis Beijing strains constructed from polymorphisms in genes involved in DNA replication, recombination and repair.

BACKGROUND: The Beijing family is a successful group of M. tuberculosis strains, often associated with drug resistance and widely distributed throughout the world. Polymorphic genetic markers have been used to type particular M. tuberculosis strains. We recently identified a group of polymorphic DNA repair replication and recombination (3R) genes. It was shown that evolution of M. tuberculosis complex strains can be studied using 3R SNPs and a high-resolution tool for strain discrimination was developed. Here we investigated the genetic diversity and propose a phylogeny for Beijing strains by analyzing polymorphisms in 3R genes. METHODOLOGY/PRINCIPAL FINDINGS: A group of 3R genes was sequenced in a collection of Beijing strains from different geographic origins. Sequence analysis and comparison with the ones of non-Beijing strains identified several SNPs. These SNPs were used to type a larger collection of Beijing strains and allowed identification of 26 different sequence types for which a phylogeny was constructed. Phylogenetic relationships established by sequence types were in agreement with evolutionary pathways suggested by other genetic markers, such as Large Sequence Polymorphisms (LSPs). A recent Beijing genotype (Bmyc10), which included 60% of strains from distinct parts of the world, appeared to be predominant. CONCLUSIONS/SIGNIFICANCE: We found SNPs in 3R genes associated with the Beijing family, which enabled discrimination of different groups and the proposal of a phylogeny. The Beijing family can be divided into different groups characterized by particular genetic polymorphisms that may reflect pathogenic features. These SNPs are new, potential genetic markers that may contribute to better understand the success of the Beijing family.

Estudo da função do gene kerV de Pseudomonas aeruginosa / Function of Pseudomonas aeruginosa kerV gene

P. aeruginosa PA14 é uma linhagem isolada de queimadura que apresenta vários fatores de patogenicidade comuns no quadro de infecção de hospedeiros filogeneticamente distintos (plantas, mamíferos ou invertebrados). O gene kerV foi revelado numa busca por mutantes atenuados em virulência em uma biblioteca de mutantes por transposons da linhagem PA14 (Rahme et al., 1997). A caracterização da linhagem D12, mutante em kerV, confirmou sua virulência atenuada (Apidianakis et al., 2005 e An et al., 2009) e resultados do transcriptoma mostraram alteração na expressão de mais de 500 genes, sendo alguns relacionados com o sistema de "quorum sensing" (Rahme et al, dados não publicados). O gene kerV está próximo à montante ao gene gloB, envolvido em detoxificação de metilglioxal, e à jusante aos genes rnhA e dnaQ, que codificam proteínas envolvidas na replicação e reparo do DNA. Este trabalho teve como objetivo estudar a função molecular do produto de kerV e a expressão dos genes do lócus kerV-rnhA-dnaQ. Análises de bioinformática indicam que a proteína KerV é uma metiltransferase dependente de S-adenosil-metionina (SAM), apresentando um domínio conservado de ligação a SAM e uma arquitetura de domínio compatível com a organização em fitas-beta e hélices-alfa alternadas descritas para a família das metiltransferases dependentes de SAM. Ela não apresenta outros domínios conservados que indiquem seu substrato de metilação. A expressão heteróloga desta proteína em E. coli, mostrou que ela é expressa de maneira parcialmente solúvel quando co-expressa com as chaperoninas GroEL/GroES em baixas temperaturas ou quando fusionada a MBP ou GST. A purificação desta proteína mostra que ela é co-eluída com a chaperonina GroEL sugerindo que para atingir sua conformação nativa ela necessita dessas proteínas acessórias. MBP-KerV purificado foi usado para ensaios "in vitro" de atividade de metiltransferase e ligação a SAM, que não foram conclusivos, pois não há certeza do seu ...

P. aeruginosa PA14 is a burn isolate multi-host pathogen strain. The screening for virulence attenuated mutants in a PA14 transposon mutant library revealed the kerV gene (Rahme et al., 1997). The characterization of D12 strain, a kerV mutant, confirmed the attenuated virulence phenotype (Apidianakis et al., 2005 and An et al., 2009) and transcriptome analysis showed the expression of more than 500 genes are affected in D12, some of these genes are related with quorum sensing (Rahme et al, unpublished data). kerV is upstream of the gloB gene, related with methylglioxal detoxification and downstream of the rnhA and dnaQ genes, both related with DNA replication and repair. The purpose of this work was to study the molecular function of KerV product and the expression of kerV-rnhA-dnaQ locus. Bioinformatics analysis indicated that KerV is a SAM dependent methyltransferase that have a conserved SAM binding domain with architecture compatible with classic alternating β-stranded and α-helical regions. KerV does not show any other conserved motif that could indicate its methylation substrate. Heterologous expression in E. coli showed that KerV is partially soluble only when co-expressed with GroeL/GroES chaperones at low temperatures or when KerV is in fusion with MBP or GST tag. During the purification process KerV was copurified with GroEL chaperone suggesting that this association may be required for the correct folding of KerV. Methyltransferase activity and SAM binding assays were done with purified MBPKerV and the results were not conclusive since the proper conformation of MBP-KerV cannot be verified. Yeast two-hybrid assays indicated that RNaseH and DnaQ are not interaction partners of KerV, suggesting that their functions are not directly related. The mutation frequency of D12 strain increased only about four times in relation to PA14, suggesting that KerV is not directly involved with DNA mismatch repair. The assays to detect methylation...

Genetics of human social behavior.

Human beings are an incredibly social species and along with eusocial insects engage in the largest cooperative living groups in the planet's history. Twin and family studies suggest that uniquely human characteristics such as empathy, altruism, sense of equity, love, trust, music, economic behavior, and even politics are partially hardwired. The leap from twin studies to identifying specific genes engaging the social brain has occurred in the past decade, aided by deep insights accumulated about social behavior in lower mammals. Remarkably, genes such as the arginine vasopressin receptor and the oxytocin receptor contribute to social behavior in a broad range of species from voles to man. Other polymorphic genes constituting the "usual suspects"--i.e., those encoding for dopamine reward pathways, serotonergic emotional regulation, or sex hormones--further enable elaborate social behaviors.

Migraña común y ciclo menstrual: estudio clínico en adolescentes / The common migraine and the menstrual cycle: clinical study in adolescents

INTRODUCCIÓN. El tratamiento de la migraña en relación con las diferentes fases del ciclo menstrual es controversial, pues en muchas ocasiones existen situaciones especiales endógenas, de tipo hormonal, y exógenas, que es necesario considerar. La literatura médica documenta que alrededor del 60 por ciento de las mujeres migrañosas presentan migraña menstrual de difícil tratamiento. El objetivo de esta investigación fue analizar esta relación entre migraña y menstruación en un grupo de pacientes atendidas en el Hospital Pediátrico Universitario William Soler. MÉTODOS. De enero a junio del 2008 se estudiaron 124 adolescentes que acudieron a la consulta de ginecología infantojuvenil y que además presentaban cefalea. Del total de la muestra fueron seleccionadas las que presentaban migraña relacionada con el ciclo menstrual (n = 70). RESULTADOS. En el 55,7 por ciento de los casos, el comienzo de la migraña se observó en la adolescencia temprana. En el 85,71 por ciento de las adolescentes existieron factores de riesgo genéticos para la migraña, y en el 50 por ciento de los casos ésta apareció en la fase premenstrual. CONCLUSIONES. La migraña común se observó con frecuencia en la fase premenstrual del ciclo, con importante participación hormonal

INTRODUCTION: Treatment of migraine related to different phases of menstrual cycle is controversial since in many occasions there are endogenous and exogenous special situations of hormonal type to be considered. Medical literature documents that about 60 percent of women presenting with migraine have a menstrual type very difficult to treat. The objective of present research was to analyze the relation between migraine y and menstruation in a series of patients seen in Wiliam Soler Children University Hospital. METHODS: From January to June, 2008 124 adolescents were studied referred to infantile-juvenile gynecology consultation and also with migraine. From total sample we selected those with migraine related to menstrual cycle (n = 70). RESULTS: In 55,7 percent of cases the migraine onset was observed in the early adolescence. In 85,71 percent of adolescents there were genetic risk factors for migraine, and in the 50 percent of cases, this appeared in the premenstrual phase. CONCLUSIONS: The common migraine was frequent in the phase above mentioned with a significant hormonal presence

Migraña común y ciclo menstrual: estudio clínico en adolescentes / The common migraine and the menstrual cycle: clinical study in adolescents

INTRODUCCIÓN. El tratamiento de la migraña en relación con las diferentes fases del ciclo menstrual es controversial, pues en muchas ocasiones existen situaciones especiales endógenas, de tipo hormonal, y exógenas, que es necesario considerar. La literatura médica documenta que alrededor del 60 por ciento de las mujeres migrañosas presentan migraña menstrual de difícil tratamiento. El objetivo de esta investigación fue analizar esta relación entre migraña y menstruación en un grupo de pacientes atendidas en el Hospital Pediátrico Universitario William Soler. MÉTODOS. De enero a junio del 2008 se estudiaron 124 adolescentes que acudieron a la consulta de ginecología infantojuvenil y que además presentaban cefalea. Del total de la muestra fueron seleccionadas las que presentaban migraña relacionada con el ciclo menstrual (n = 70). RESULTADOS. En el 55,7 por ciento de los casos, el comienzo de la migraña se observó en la adolescencia temprana. En el 85,71 por ciento de las adolescentes existieron factores de riesgo genéticos para la migraña, y en el 50 por ciento de los casos ésta apareció en la fase premenstrual. CONCLUSIONES. La migraña común se observó con frecuencia en la fase premenstrual del ciclo, con importante participación hormonal(AU)

INTRODUCTION: Treatment of migraine related to different phases of menstrual cycle is controversial since in many occasions there are endogenous and exogenous special situations of hormonal type to be considered. Medical literature documents that about 60 percent of women presenting with migraine have a menstrual type very difficult to treat. The objective of present research was to analyze the relation between migraine y and menstruation in a series of patients seen in Wiliam Soler Children University Hospital. METHODS: From January to June, 2008 124 adolescents were studied referred to infantile-juvenile gynecology consultation and also with migraine. From total sample we selected those with migraine related to menstrual cycle (n = 70). RESULTS: In 55,7 percent of cases the migraine onset was observed in the early adolescence. In 85,71 percent of adolescents there were genetic risk factors for migraine, and in the 50 percent of cases, this appeared in the premenstrual phase. CONCLUSIONS: The common migraine was frequent in the phase above mentioned with a significant hormonal presence(AU)

Influencia de factores genéticos sobre la orientación sexual humana: una revisión / Influence of genetic factors on human sexual orientation: review

La orientación sexual humana es un carácter complejo influido por varios genes, experiencias vivenciales y factores socioculturales. Estos factores interactúan y producen un patrón característico de orientación sexual hacia el sexo opuesto, pero existen excepciones, como la bisexualidad y la homosexualidad. Esta parece ser más frecuente en hombres que en mujeres. Es un carácter multifactorial. El método tradicional para el estudio genético de características del comportamiento consideradas multifactoriales es analizar si presentan agregación familiar. Para separar la importancia de los factores genéticos de los ambientales en esta agregación, se compara la concordancia para el carácter entre gemelos monocigóticos, dicigóticos y hermanos adoptados criados juntos. Estos estudios revelan que la agregación familiar es más evidente para la homosexualidad masculina que para la femenina. Utilizando el método del umbral para caracteres multifactoriales, y variando la frecuencia de homosexualidad en la población entre 4 y 10%, se han estimado valores de heredabilidad de la misma que oscilan entre 0,27 y 0,76. En 1993, utilizando métodos moleculares, se encontró ligamiento entre homosexualidad y la región cromosómica Xq28; sin embargo, estudios posteriores no lo confirman. Recientemente, la búsqueda amplia en el genoma mostró valores sugerentes o significativos de ligamiento en las regiones 7q36, 8p12 y 10q26, con genes candidatos de interés. La desviación en la proporción de inactivación del cromosoma X en las madres de homosexuales parece apoyar la presencia de genes relacionados con la orientación sexual en este cromosoma. Aún falta mucho por conocerse en relación a la genética de la homosexualidad humana.

Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality.

La artrosis como enfermedad genética / Osteoarthritis as a genetic condition

La artrosis es un ejemplo de enfermedad compleja, que se origina por la interacción de factores genéticos y ambientales. En este trabajo revisamos los diferentes tipos de estudios que permiten analizar la contribución de los factores genéticos a la patogenia de las enfermedades complejas y los genes cuyos polimorfismos se han relacionado con el riesgo de desarrollar artrosis.Dado el importante beneficio que aporta la cirugía a los pacientes con artrosis avanzada, cabría plantearse si estos estudios genéticos tienen realmente alguna utilidad. La respuesta es claramente afirmativa. Por un lado, el conocimiento de los factores genéticos implicados en la aparición y el desarrollo de la artrosis puede permitir identificar y controlar subgrupos de individuos de mayor riesgo en fases precoces. Por otro lado, la identificación de los genes involucrados puede llevar a determinar nuevas dianas terapéuticas que permitan frenar de manera eficaz el desarrollo del proceso, algo que no podemos ofrecer a nuestros pacientes en la actualidad(AU)

Osteoarthritis is an example of a complex disease, which arises from the interaction of genetic and environmental factors. In this paper we review the different types of studies that can be conducted in order to analyze the contribution of genetic factors to the pathogenesis of complex diseases as well as the genes whose polymorphisms have been associated to the risk of developing osteoarthritis.The significant benefits that surgery can offer patients with advanced-stage osteoarthritis beg the question of whether there genetic studies are really of any use. The answer is clearly in the affirmative. On the one hand, an awareness of the genetic factors involved in the onset and development of osteoarthritis may help identify and control subgroups of individuals who are at a higher risk at an early stage. Furthermore, identification of the genes involves could help discover new therapeutic targets that may lead to effectively halting the process, which is something we cannot do with our patients at present(AU)