New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes

Background Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes.

Background: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

Assessing cervical spine and craniofacial morphology in Class II and Class III malocclusions: A geometric morphometric approach.

To compare craniofacial and cervical morphology between skeletal Classes II and III applying Geometric Morphometric Methods (GMM). Twenty-six cervical and craniofacial landmarks of 40 Class II and 39 Class III individuals were digitalized on lateral cephalograms. Procrustes ANOVA, generalized Procrustes, principal component analyses, and thin-plate spline function were applied to assess the pattern of shape variation of craniofacial structure and the cervical spine in relation to skeletal classes. Compared with Class III, Class II individuals presented a maxillary protrusion, mandibular retrusion, shorter mandibular corpus, posterior mandibular ramus rotation, anterior cranial base rotation, and a smaller centroid size. Furthermore, a forward and smaller cervical spine were observed. With GMM, the shape and size differences between skeletal classes can be analyzed visually and numerically.

Relationship between craniocervical posture and skeletal class: A statistical multivariate approach for studying Class II and Class III malocclusions.

Objective: To investigate the relationships between craniocervical posture and skeletal Class in cephalometric radiographs of adult subjects.Methods: Sixty-five cephalometric radiographs were classified after Delaire, as skeletal Class II and III. The craniocervical posture was evaluated using the variables proposed by Solow (1976) and Rocabado (1983). In order to test the null hypothesis (absence of an association between craniocervical posture and skeletal Class), uni- and multivariate statistical protocols were carried out.Results: Skeletal Class II presented a more posterior rotation of the ramus in relation to the cranium and a more extended head than skeletal Class III. Additionally, significant correlations were observed in Class II individuals between the rotation of mandibular ramus and cervical lordosis, as well as between rotation of mandibular ramus and craniocervical posture.Discussion: The findings of this research may help to understand the contradictory results described in clinical literature about the effect of skeletal class on craniocervical posture.

Morphological consequences of artificial cranial deformation: Modularity and integration.

The cranium is an anatomically complex structure. One source of its complexity is due to its modular organization. Cranial modules are distinct and partially independent units that interact substantially during ontogeny thus generating morphological integration. Artificial Cranial Deformation (ACD) occurs when the human skull is intentionally deformed, through the use of different deforming devices applied to the head while it is developing. Hence, ACD provides an interesting example to assess the degree to which biomechanical perturbations of the developing neurocranium impact on the degree of morphological integration in the skull as a whole. The main objective of this study was to assess how ACD affects the morphological integration of the skull. This was accomplished by comparing a sample of non-deformed crania and two sets of deformed crania (i.e. antero-posterior and oblique). Both developmental and static modularity and integration were assessed through Generalized Procrustes Analysis by considering the symmetric and asymmetric components of variation in adults, using 3D landmark coordinates as raw data. The presence of two developmental modules (i.e. viscero and neurocranium) in the skull was tested. Then, in order to understand how ACD affects morphological integration, the covariation pattern between the neuro and viscerocranium was examined in antero-posterior, oblique and non-deformed cranial categories using Partial Least-Squares. The main objective of this study was to assess how ACD affects the morphological integration of the skull. This was accomplished by comparing a sample of deformed (i.e. antero-posterior and oblique) and non-deformed crania. Hence, differences in integration patterns were compared between groups. The obtained results support the modular organization of the human skull in the two analyzed modules. The integration analyses show that the oblique ACD style differentially affects the static morphological integration of the skull by increasing the covariance between neuro and viscerocranium in a more constrained way than in antero-posterior and non-deformed skulls. In addition, the antero-posterior ACD style seems to affect the developmental integration of the skull by directing the covariation pattern in a more defined manner as compared to the other cranial categories.

Comparación cefalométrica entre un paciente acromegálico y su hermano gemelo / Cephalometric comparison between an acromegalic patient and his twin brother

La acromegalia es una enfermedad caracterizada por una desfiguración somática de progresión lenta causada por la sobreproducción de hormona de crecimiento (GH) y factor de crecimiento insulinoide tipo 1 (IGF-1), predominantemente asociada con un adenoma hipofisario. La manifestación más evidente a nivel facial es un prognatismo mandibular por exceso de crecimiento de la mandíbula. El propósito del presente trabajo fue realizar una comparación morfológica craneofacial mediante análisis cefalométrico y superposición cefalométrica entre un paciente con diagnóstico de acromegalia y su hermano gemelo que no presenta la enfermedad. Nuestros resultados mostraron que en el hermano con acromegalia existe un significativo aumento del tamaño de la silla turca, un desplazamiento hacia anterior del maxilar y mandíbula, siendo más marcado el desplazamiento mandibular. El cambio morfológico que experimenta la mandíbula en la acromegalia es atribuido principalmente al crecimiento de la rama mandibular por aumento de la unidad condilar.

Acromegaly is characterized by a slowly progressive somatic disfigurement caused by the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF 1), mainly associated with a pituitary adenoma. The most evident facial manifestation is mandibular prognathism due to excessive growth of the jaw. This work aimed to perform a craniofacial morphological comparison through cephalometric analysis and cephalometric superimposition of a patient diagnosed with acromegaly and his twin brother without the disease. Our results showed that the acromegalic patient has a significant increase in the size of the sella turcica, an anterior displacement of the maxilla and mandible, the mandibular displacement being more marked. The morphological change of the mandible in acromegaly is mainly attributed to the growth of the mandibular ramus due to an increase in the condylar unit.

A small, new gerbil-mouse Eligmodontia (Rodentia: Cricetidae) from dunes at the coasts and deserts of north-central Chile: molecular, chromosomic, and morphological analyses.

A small, new species of gerbil rodents of the genus Eligmodontia from the southwestern dunes of the Atacama Desert in northern Chile is described; the genus had not been reported for this western lowland region. Our description is based on cytogenetic and molecular data, as well as cranial and external morphology. In order to support this hypothesis, we studied 27 specimens captured in Playa Los Choros (Coquimbo) and Copiapó (Atacama), comparing them with samples of all the extant species of the genus. Nineteen individuals consistently showed 2N=50, FN=48, with telocentric chromosomes and G-bands identical to those of the geographically northeastern E. hirtipes; these two groups were geographically separated by E. puerulus (2N = 34, FN = 48). The phylogenetic analysis of 56 Eligmodontia cytochrome-b gene sequences yielded a maximum-likelihood phylogenetic tree where the new species formed a divergent and well-supported clade within the genus, which was also confirmed by unweighted parsimony, minimum evolution, and Bayesian analyses. The new species has K2P genetic distances of 12.8% from the geographically distant E. hirtipes, and 10.3% from E. puerulus. Axes 1 and 2 of Principal Component Analysis based on 12 body and skull measurements clearly separated the new species, the latter having a smaller head+body length (70.6 +/- 3.4 mm, n = 17) and lower weight (11.9 +/- 1.9 g, n = 20). We provide strong evidence to recognize a distinct new western lineage within Eligmodontia genus, Eligmodontia dunaris sp. nov., for which we give a complete taxonomic description and a hypothetical biogeographic scenario. The new species should be considered endangered, due to its level of endemism, its low population numbers (which can be occasionally increased after a blooming desert) and its fragile dry habitat patchily distributed near the Atacama Desert.