Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Spatial summation in the receptive field periphery of two types of on-center neurons in cat retina

Peripheral annuli with the same inside diameters but variable outside diameters were used to study the peripheral summing properties of Group I and Group II cells ( Winters, Hickey and Pollack, 1973). The results showed that Group I and Group II cells could be differentiated on the basis of their responses to changes in the size of peripheral annuli. Group I cells showed spatial summation of both the on-excitation and the off-excitation of on-off responses elicted by peripheral annuli. This finding was not found to be dependent upon the location of the target in the receptive field periphery. The effect of target size on the response of Group II cells was found to be dependent upon the location of the target in the receptive field periphery. If the inside portion of the annulus was near the receptive field center, in the on-off zone, then small increases in target size produced an increase in the strength of the onexcitation whereas large changes in target size lead to a decrease in the strength of the onexcitation. Off-excitation showed spatial summation across the entire receptive field periphery. It was possible to demonstrate linear spatial summation in the receptive field periphery of Group II cells but not Group I cells. Avec des anneaux périphériques de mémes diamètres internes et de diamètres externes variables, onétude les propriétés de sommation périphérique des cellules des groupes I et II ( Winters, Hickey et Pollack, 1973). On peut différentier ces groupes par leurs réponses aux changements de taille des anneaux périphériques. Le groupe I montre une sommation spatialeàla fois pour l'excitation on et l'excitation off des réponses on-off produites par les anneaux périphériques. Ce résultat ne dépend pas de la position de la cibteàla périphérie du champ récepteur. Au contraire l'effet de la taille de la cible sur la réponse des cellules du groupe II dépend de la position de la cible dans la périphérie du champ récepteur. Si la partie interne de l'anneau est près du centre du champ récepteur, dans la zone on-off, une petite augmentation de dimension de la cible augmente l'amplitude de l'excitation on, tandis qu'une grande variation de taille de la cible fait décroître l'amplitude de l'excitation on. L'excitation off montre une sommation spatiale dans toute la périphérie du champ récepteur. On peut démontrer la linéaritéde la sommation spatíale dans la périphérie du champ récepteur pour les cellules du groupe II, mais pas pour celles du groupe I. Periphere Ringe mit gleichem Innendurchmesser aber verschiedenen Aussendurchmessern wurden dazu benutzt, die peripheren Summationseigenschaften von Zellen der Gruppe I und Gruppe II zu untersuchen, (vgl. Winters, Hickey und Pollack, 1972). Die Ergebnisse zeigten, dass die Zellen der Gruppe I und der Gruppe II aufgrund ihrer Antworten aufÄnderungen in der Grösse peripherer Ringe differenziert werden konnten. Die Zellen der Gruppe I zeigten eine räumliche Summation sowohl der On-Erregung als auch der Off-Erregung bei von peripheren Ringen hervorgerufenen On-Off-Antworten. Eine Abhängigkeit vom Ort des Testreizes in der Peripherie des rezeptiven Feldes wurde nicht gefunden. Dagegen wurde eine Abhängigkeit des Effektes der Testzeichengrösse auf die Antwort von Zellen der Gruppe II vom Ort des Testreizes in der Peripherie des rezeptiven Feldes gefunden. Befand sich die Ringinnenfläche in der Nähe des Zentrums des rezeptiven Feldes d.h. in der On-Off-Zone, so verursachten kleine Vergrösserungen der Testzeichengrösse einen Anstieg in der Stärke der On-Erregung, während grosse Veränderungen in der Testzeichengrösse zu einem Abfall in der Stärke der On-Erregung führten. Die Off-Erregung zeigte eine räumliche Summationüber die gesamte Peripherie des rezeptiven Feldes. Es war möglich, eine lineare räumliche Summation in der Peripherie des rezeptiven Feldes von Zellen der Gruppe II, aber nicht von solchen der Gruppe I zu demonstrieren. Кoльцa, pacпoлaгaeмыe нa пepнфepии peцeптнвнoгo пoля, имeвшиe oдинaкoвыe внyтpeнниe диaмeтpы, нo пepeмeнныe внeщниe диaмeтpы, были иcпoльзoвaны для изyхeния ocoбeннocтeй пpocтpaнcтвeннoй cyммaцни I и пoй гpyпц клeтoк Winters, Hickey and Pollack, 1972). Peзyльтaты пoкaзывaют, хтo клтeтки I и II гpyпп мoгyт paзлихaтьcя нa ocнoвaнии их peaкций пpи измeнeнии вeлихины кoльцa. Пepвaя гpyппa клeтoк oбнapyзивaлa пpocтpaнcтвeннyю cyммaцию кaк “on” — вoзбyздeния, тaк и “off” — вoзбyздeния “on-off” peaкций, вызывaeмых кoньцoм нa пepифepии peцeптнвнoгo пoля. Этo нe зaвиcилo oт pacпoлoзeния oбьeктa нa пepифepии peцeптивнoгo пoля. Bлияниe вeлнхины oбьeктa нa peaкцию клeтoк втopoй гpyппы зaвиcилo oт пoлoзeния oбъeктa нa пepифepии peцeптивнoгo пoля. Ecли внyтpeнняя хacть кoляцa былa блнзкo к цeнтpy peцeптнвнoгo пoля, в “on-off” зoнe, тo нeбoльщoe yвeлихeниe вeлихины oбъeктa ьызывaлo yвeлихeниecнлы “on” — вoзбyздeния”, тoгдa кaк бoльшиe измeнeния вeлихины oбъeктaвeлик yмeньшeнию cилы “on” — вoзбyздeния. “Off” — вoзбyздeниe oбнapyзивaлo пpocтpaнcтвeннyю cyммaцию в пpeдeлaх вceй пepифepии peцeптивнoгo пoля. Былo вoзмoзнo oбнapyзить линeйнyю пpocтpaнcтвeннyю cyмaцию нa цepнфepии peцeптивнoгo пoля для клeтoк IIoй гpyппы, нo нe для клeтoк Ioй гpyппы

PCOS Forum: Research in polycystic ovary syndrome today and tomorrow

Objective To summarize promising areas of investigation into polycystic ovary syndrome (PCOS) and to stimulate further research in this area. Design Summary of a conference held by international researchers in the field of polycystic ovary syndrome. Results Potential areas of further research activity include the analysis of predisposing conditions that increase the risk of PCOS, particularly genetic background and environmental factors, such as endocrine disruptors and lifestyle. The concept that androgen excess may contribute to insulin resistance needs to be re-examined from a developmental perspective, since animal studies have supported the hypothesis that early exposure to modest androgen excess is associated with insulin resistance. Defining alterations of steroidogenesis in PCOS should quantify ovarian, adrenal and extraglandular contribution, as well as clearly define blood reference levels by some universal standard. Intraovarian regulation of follicle development and mechanisms of follicle arrest should be further elucidated. Finally, PCOS status is expected to have long-term consequences in women, specifically the development of type 2 diabetes, cardiovascular diseases and hormone dependent cancers. Identifying susceptible individuals through genomic and proteomic approaches would help to individualize therapy and prevention. Conclusions There are several intriguing areas for future research in PCOS. A potential limitation of our review is that we focused selectively on areas we viewed as the most controversial. © 2011 Blackwell Publishing Ltd