RUSNANO and AmBAR Announce the Business Plan Competition of Nanotech Projects 

    AmBAR creates a unique platform to facilitate the exchange of knowledge, ideas, and business contacts between technology entrepreneurs, professionals, and investors. The organization is also dedicated to accelerating access to capital for innovative projects and developing technology partnerships between Russia, Ukraine and other FSU countries and the United States. Through various seminars and conferences AmBAR provides educational programs that help entrepreneurs refine their business plans, and advance their product development and marketing efforts.

Ambar’s Mission:

·       To provide a networking platform for technology entrepreneurs, venture capital investors, and other business professionals from Russian, Ukraine and other CIS countries who are interested in innovation and commercialization of high technology products.

·       To educate, showcase, and support entrepreneurs in Russia, Ukraine and other CIS countries as they seek equity capital, corporate partners, and grow their companies globally.

·       To enhance all aspects of technology partnership between the United States and the countries of the former Soviet Union. 

SVOD Conference is right around the corner and we have an amazing lineup of speakers! Register today and don’t miss out on this unique networking opportunity!

 

    This is a not to be missed event for the entrepreneurs and the Venture Capital community. This year’s theme will drive a very exciting Agenda exploring “re-invention” as it affects the startup process on multiple levels — technologies, business models, financing, monetizing and team building.

 

 

• Vinod Khosla, Founding Partner, Khosla Ventures
• Charles Giancarlo, Managing Director, Silver Lake
• Steve Blank, Serial Entrepreneur; Founder, Epiphany; Lecturer, Stanford University, Graduate School of Engineering
• Sergei Beloussov, CEO, Parallels
• Ron Conway, Founding General Partner, Angel Investors LP
• Jason Pressman, General Partner, Shasta Ventures
• Adam Lashinsky, Editor at large, Fortune magazine; regular panelist and business commentator for Fox network programs
• Esther Dyson, Director, 23andMe, Principal, EDventure Holdings (sold to CNet), investor in Flickr and del.icio.us (both sold to Yahoo!) & Medstory (sold to Microsoft)
• Jeff Crow, General Partner, Norwest Venture Partners
• Vivek Mehra, General Partner, August Capital
• Ping Li, General Partner, Accel Partners
• Kittu Kolluri, General Partner, New Enterprise Associates
• Franklin Pitch Johnson, Founding Partner, Asset Management Company
• Peter Loukianoff, Partner, Almaz Capital Partners
• Guy Kawasaki, Managing Director, Garage Technology Ventures
• Pavel Pogodin, Partner, Sughrue Mion LLP
• Dmitry Dubograev, Partner, Femida LLP
• Leonid Gozman, Board Member, RUSNANO
• Mikhail Chuchkevich, Director, Project Office, RUSNANO
• Dmitry Vasuytinsky, Managing Partner, Allianz Asset Management
• Yan Ryazantsev, Investment Director, Russian Venture Company
• Bo Parker, Managing Director, Center for Technology and Innovation, PriceWaterhouseCoopers
• Phil Libin, CEO, Evernote
• Vlad Shmunis, CEO, RingCentral, Sequoia-backed company
• Matthew Trevithick, General Partner, Venrock
• Eric Buatois, General Partner, Sofinnova Ventures
• Vish Makhijani, COO, Zynga
• Vimal Solanki, Vice President, McAfee
• Evgeni Utkin, CEO, Kvazar-Micro, acquired by Sitronics, voted the Best Ukrainian Entrepreneur
• Greg Shenkman, General Partner, Exigen Capital, formerly CEO of Genesys, sold to Alcatel for $1.9B
• Mike Selfridge, Northern California Region Manager, Silicon Valley Bank

Whether you are looking for a deal flow, funding, information or networking – SVOD 2009 is the place to be! - WWW.SVOD.ORG 

 

 

Date: December 9-10, 2009

Location: Computer History Museum, Mountain View, Silicon Valley, CA

To Register: http://www.svod.org/

 

Russian Corporation of Nanotechnologies (RUSNANO) and American Business Association of Russian-speaking Professionals (AmBAR) announce the Business Plan Competition cor projects and companies working in the field of nanotechnology. Origination of the project may come from any country or person all over the world, but its implementation or some part of implementation has to be completed in Russia. In 2009 the nominees for the contest are pre-selected by AmBAR among the participants of the Fifth Annual High Tech Investment Conference SVOD 2009. For more information, please go to: http://www.svod.org/ or e-mail to info@ambarclub.org

The projects are evaluated by the following criteria:

• nanotechnology application;
• scientific and technical feasibility of the project;
• quality and feasibility of the business-plan;
• steps already made towards project implementation.

The winner of the competition receives the RUSNANO award and the prize in the amount of 300,000 rubles (~$10,000).

For more details, please see the Contest terms and conditions (in Russian)

A recent GWAS study identified the 3′ region of the liver- (not brain) expressed PECR gene (rs7590720(G) and rs1344694(T)) on chromosome 2 as a risk factor for alcohol dependency.  These results, as reported by Treutlein et al., in “Genome-wide Association Study of Alcohol Dependence” were based on a population of 487 male inpatients and a follow-up re-test in a population of 1024 male inpatients and 996 control participants.

The authors also asked whether lab rats who – given the choice between water-based and ethanol-spiked beverages over the course of 1 year – showed differential gene expression in those rats that were alcohol preferrers vs. alcohol non-preferring rats.  Among a total of 542 genes that were found to be differentially expressed in the amygdala and caudate nucleus of alcohol vs. non-alcohol-preferring rat strains,  a mere 3 genes – that is the human orthologs of these 3 genes – did also show significant association with alcohol dependency in the human populations.  Here are the “rat genes” (ie. human homologs that show differential expression in rats and association with alcohol dependency in humans): rs1614972(C) in the alcohol dehydrogenase 1C (ADH1C) gene, rs13273672(C) in the GATA binding protein 4 (GATA4) gene, and rs11640875(A) in the cadherin 13 (CDH13) gene.

My 23andMe profile gives a mixed AG at rs7590720, and a mixed GT at rs1344694 while I show a mixed CT at rs1614972, CT at rs13273672 and AG at rs11640875.  Boooring! a middling heterozygote at all 5 alcohol prefer/dependency loci.   Were these the loci for chocolate prefer/dependency I would be a full risk-bearing homozygote.

BY Kate Rockwood -  Web de www.fastcompany.com

1. Melinda Gates, cochair and trustee, Bill & Melinda Gates Foundation
Nimbly throwing the foundation’s bucks behind both big-picture, tech-oriented, long-term solutions and modest, immediate action plans, Melinda Gates is a formidable force in the fight for health care in developing nations.

2. Anthony Atala, director, Wake Forest Institute for Regenerative Medicine
The first doctor to bioengineer a human bladder and successfully implant it in a human, Anthony Atala and his staff are now busy growing 22 different tissues–from heart valves to fingers–planting them at the forefront of this (ahem) growing field.

3. Jay Parkinson, founder, Hello Health
Mixing non-conventional payment structure (monthly subscription fee, PayPal but no insurance) and eyebrow-raising communications (e-mail, instant messaging, even house visits), Jay Parkinson’s Hello Health offers a wildly popular alternative to the current model of high insurance costs and eight-minute office visits.

4. James Heywood, cofounder and chairman, PatientsLikeMe
Following his brother’s diagnosis with ALS, Heywood launched PatientsLikeMe–think of it as a social-networking health site on massive steroids. People with like diseases input clinically validated data, helping them empathize and learn from others’ experiences, while physicians and researchers can tap into the rich info to further treatments.

5. Thomas Frieden, director, Center for Disease Control & Prevention
Picked by Obama to head the Center for Disease Control & Prevention, Frieden earned his stripes first by fighting tuberculosis in India and then as the vocal force behind many of NYC’s most aggressive public health initiatives in recent years–from posting calories on menus and banning trans fat, to reducing public smoking–proving that sometimes the most creative way to tackle a problem is head on.

6. Peter Neupert, vice president of Health Solutions Group, Microsoft
A multi-trillion-dollar industry still limping along on handwritten notes? Not for much longer, if Neupert and his HealthVault team, part of Microsoft’s electronic health record initiative, have anything to say about it.

7. Steve Case, founder and CEO, Revolution Health Group
First he cofounded AOL, then Steve Case turned his attention to health care. Now everyday users of the extensive online portal can create profiles, answer each other’s queries, rate their doctors, and deploy an army of widgets–all aimed at democratizing health information.

8. Hans Rosling, professor of global health, Karolinska Institute in Sweden
We’ll admit it: Rarely do we think of statistics as a particularly creative field. But Hans Rosling’s trend-revealing software–which first garnered major attention when it helped identify a new paralytic disease in Africa–is dramatically reshaping views of global health and poverty trends.

9. Douglas Melton, codirector, Harvard Stem Cell Institute
Douglas Melton’s pioneering work to create new stem-cell lines that could replace malfunctioning cells in the pancreas that are linked to diabetes would earn him praise enough. But it’s his creative solution to use adult skin cells–thereby sidestepping the embryonic stem cell debate entirely–that will smartly keep Melton and his work clipping along, sans controversy.

10. Anne Wojcicki, cofounder, 23andMe
Others may have figured out how to crack the DNA code, but it’s Anne Wojcicki who’s lured the masses (and Silicon Valley celebs) to offer up their saliva for private genetic testing during swank “spit parties.” She and her partner, Linda Avey, are now compiling customers’ privacy-protected data into a research-ready database.

Reilu puoli vuotta sitten lähetin sylkykupin 23andme:lle ja muutamalla satasella sain siis käytännössä 14 megasen tiedoston, jossa on perimäni tärkeimmät variaatiot (SNP:t). Nyt 23andme on päivittäny palvelujaan ja tarjoaa asiakkailleen “sukulaistenetsintäpalvelun” (relative finder) beta-version. Se etsii geenitietojen perusteella kaikkien testattujen joukosta kaukaisiakin sukulaisia, ja ainakaan tällä hetkellä käyttö ei maksa mittään ylimääräistä. Idea perustuu sille, että ihmisen perintötekijät eivät määräydy ihan satunnaisesti äidiltä ja isältä vaan periytyvät isommissa kromosomipätkissä. Ihmisellä on tupla-kromosomisto: toinen kromosomi saadaan isältä ja toinen äidiltä. Kun sukusolut muodostuvat meioosissa täytyy tästä tuplamäärästä valita vain puolet niin että saadaan yksinkertainen kromosomisto. Tuo valikoituminen ei tapahdu satunnaisesti niin että jokainen emäspari tai edes geeni arvottaisiin satunnaisesti jommasta kummasta kromosomista. Valikoituminen tapahtuu pitemmissä pätkissä (ns. cross-over prosessi), joissa voi olla useita miljoonia emäspareja. Tätä voi verrata vähän siihen, että kaksi eriväristä kengännauhaa leikataan pätkiksi ja sitten puolet näistä pätkistä solmuilla yhdistetään yhdeksi raidalliseksi kengännauhaksi. Koska ihmisen perintötekijät sisältävät gigakaupalla tietoa voidaan hyvin suurella todennäköisyydellä sanoa, että kaksi henkilöä ovat sukua toisilleen, jos heidän geeneistään havaitaan riittävän iso pätkä (tai useita pätkiä) täysin identtistä materiaalia. Siis on tietenkin mahdollista, että pätkät ovat identtisiä aivan sattumalta, mutta mitä pitempi pätkä identtistä materiaalia löytyy sitä varmempi  voi olla, että henkilöt ovat sukulaisia keskenään. Tällä menetelmällä voi löytää hyvin pikkusen serkun, jonka kanssa on yhteinen esi-isä tai -äiti kahdeksan sukupolven takaa, eli 1700-luvulle asti päästään. Silloin yhteisten perintötekijöiden osuus tuon esivanhemman kanssa on jotain (1/2)^8 eli 0.3% ja nämä kaukaiset serkukset saattavat löytää hyvin lyhyen pätkän yhteisiä geenejä. Jos mennään tästä pidemmälle niin pätkät alkavat olla jo niin lyhyitä, että jäljellä on enää kohinaa. Jos mennään vaikka 1500-luvulle asti (20 sukupolvea) kaikki tällöin eläneiden ihmisten geenimateriaali on pirstoutunut ja hajaantunut ympäri populaatiota, eikä mitään yhteistä ole mahdollista löytää.

Tää oli siis teoria, entä sitten käytäntö. Klikkasin sisään ja katsoin. 94 sukulaista löytyi. Voiko olla mahdollista? Voi. Vaikka osa saattaa olla ihan statistisen virheen takia väärin niin suuruusluokka on todennäköisesti kyllä oikein. Tästä voi varmistua ihan yksinkertaisella laskulla: kyseisen lafkan kautta geenitestanneita suomalaisia on pikemminkin satoja kuin tuhansia, mutta tämä riittää jo siihen, että kaukaisia sukulaisia löytyy monta. Arvioidaan, että suomalaisia oli 1700-luvun loppupuolella noin puoli miljoonaa ja heistä 256 on esivanhempia 8. polvessa. Siis oletetaan, että kaikki ovat eri henkilöitä, vaikka kyllähän sisäsiittoisuus Suomessa lienee korkea. Tällöin noin 13% todennäköisyydellä kahdella satunnaisesti valitulla suomalaisella henkilöllä on ainakin yksi yhteinen esi-isä tai -äiti kahdeksannessa polvessa. Siis tämä nyt on tietenkin “tupakka-askin takakanteen tehty lasku”, mutta havaittu suuri määrä sukulaisia selittyy sillä, että väestö on kasvanut viime vuosisadoilla hyvin nopeasti. Tällä hetkellä beta-versiossa ei pysty sukulaiskandidaatteihin ottamaan yhteyttä paitsi niihin, jotka osallistuvat kokeiluun. Tämä on vähän harmi, sillä kovasti kiinnostaisi tietää kuka on tuo Englannissa oleva pikkumpiserkku neljännessä sukupolvessa. Jenkkilässä oli tietenkin kasapäin kaukaisia sukulaisia ja muutama Norjassa, mutta sen tiesinkin, ihan sukupuun mukaan.

Testisaiteille on viime aikoina näkynyt aika paljon ihmisiä, jotka epätoivoisenkin oloisesti etsivät geenitiedoillaan edes kaukaisia sukulaisia testisaiteilla lurkkeroivien muiden ihmisten joukosta. Näillä ihmisillä ei ole välttämättä edes tietoa vanhemmistaan. Jotkut ehkä löytävät juurensa tämän avulla, toiset eivät. Ainakin testaamisten yleistyminen lisää todennäköisyyttä, että ihmiset löytävät kadonneita sukulaisiaan ja tuo relative finder on kyllä näppärä työkalu.

–

Onko testaamisesta sitten mitään hyötyä, jos ei satu olemaan kiinnostunut penkomaan sukulaisiaan geeniensä avulla. Geenitutkimus on vielä aika lapsenkengissään, mutta snpediasta voi katsoa kiinnostaako erityisesti jonkun ominaisuuden tai riskin tietäminen. Esim. tämä. Jokainen voi sitten itse muodostaa mielipiteensä siitä, kuinka tärkeää on ylipäätänsä tietää geneettisten variaatioiden vaikutus. Ihmisten mielikuvissa geenit ovat usein joko hyviä “normaaleja” geenejä tai sitten “geenivirheitä”, mutta aika harvoin jollain geenillä on pelkästään positiivisia tai negatiivisia vaikutuksia. Kaikki vaikuttaa kaikkeen. Jos neo-darwinisteihin on uskominen olemme oikeastaan niitä Platonin luolavertauksen vankeja, jotka näkevät geenien luoman todellisuuden vain varjoina seinillä. Neo-darwinistien mukaan kun elämän päänäyttelijöitä eivät ole niinkään yksilöt (koska ovat kuolevaisia), eivätkä suvut tai kansat (nousevat ja kukistuvat) eivätkä edes lajit (koska nekin  kuolevat sukupuuttoon), vaan geenit, jotka ovat ikuisia ja käyttävät häikäilemättömästi hyväksi meitä ihmisiä kuljetusvälineinään (“luuranko sisällämme”). Yleisesti tiedon lisääntyminen geenien vaikutuksesta voi auttaa meitä tekemään maailmasta vähän onnellisempi paikka elää, jos vaan käytämme tietoa hyvässä tarkoituksessa.

Tiedon lisääntyminen voi tietenkin myös johtaa eettisiin ongelmiin. Niin kauan kun yhteiskunta huolehtii tasa-arvoisesti sairauden sattuessa eikä syrji geenien perusteella vaikka työnhaussa on luultavasti aivan se ja sama vaikka laittaisi kaikki geeninsä kotisivulleen. Itse katsoin kuitenkin parhaimmaksi olla jakamatta raaka-dataani, koska en tiedä mitä yllätyksiä uusien tutkimusten valossa niistä voi löytyä. Lisäksi en tiedä miten tulevaisuudessa suhtaudutaan geenien avulla pääteltyihin sairausriskeihin. Trendi on ollut Euroopassakin siirtyä yksityisiin sairausvakuutuksiin ja jakaa ihmisiä riskiluokkiin, joiden perusteella vakuutusmaksu määräytyy. USA:ssa on säädetty Genetic Information Nondiscrimination Act (GINA) vuonna 2008 ja lienee epätodennäköistä, että geenitietojen perusteella joutuisi syrjityksi lähitulevaisuudessa. Mutta kuka tietää miten tilanne kehittyy. Jos vakuutusyhtiöni tietäisi, että sairastun todennäköisesti johonkin vaikeaan sairauteen, joka olisi miljoonatappio vakuutusyhtiölle, niin toki yhtiö säätelemättömässä markkinataloudessa tekisi kaikkensa, että tappiot minimoituisivat. Kauhukuviakin voi tässä maalailla ihan niin paljon kuin jaksaa. Duunissa huumetesti josta salaa testataan geenit sairausriskien takia. Vakuutusyhtiösi lurkkeroimassa geenitestisaitilla keräämässä geenitietosi “ystävänä”. Geenitestisaitti joka kräkätään tai vuotaa datan. Keksi oma skenariosi ja kirjoita dekkari. Kaikessa täytyy muistaa, että geenit ovat jokaisessa solussasi, joten ihan lähiaikoina ei ole odotettavissa tekniikkaa jolla “vialliseen geeniin” saataisiin pätchit.

October’s been a busy month and so I haven’t had much time to post. But busy means interesting, and so I have lots of things to write about, it just doesn’t really get done. Some of the posts I have in the pipeline — mostly just as titles with scarce notes to remind myself what they mean:

The commenting conundrum: about where and why scientists do or don’t comment on scientific articles.

Responding to “them”: about the whos, whats, wheres, whens, whys, and hows of criticism and responding (or not) to it; mostly on the web but also off.

A detailed look into PLoS’s article-level metrics data: it’s open, so why not? And the results might just surprise you.

Thoughts from Science Commons Salon: with the amount of brainpower in that room, I’m surprised it didn’t explode. In fact, I’m surprised the whole town of Mountain View hasn’t exploded from sheer intellect yet.

So yeah, plenty to write about, sometime. I saw Pete Binfield of PLoS at the SC Salon and he joked that I was falling behind, reposting things that he’d posted a whole four days ago. Makes me want to start the Slow Blog movement…

Those posts will probably keep simmering for a little while. In the meantime, I haven’t been completely idle – in the last three weeks, I’ve written three blog posts for 23andMe’s Spittoon on genetic association studies on glaucoma, bone mineral density, and blood-related traits. Another one is set to come out early next week. So if you haven’t been tuning in regularly to the Spittoon, now you know where else to find me!

Fuente: Technology Review

Craig Venter y sus colegas comparan los tests genéticos destinados a los consumidores y sugieren modos de hacer que sean más útiles.

El genetista Craig Venter y sus colegas han puesto a prueba dos de los principales servicios genómicos para consumidores, declarando que la industria de reciente creación es prometedora pero que aún está en una fase muy inicial en términos de la utilidad de la información que proporciona.

Venter, fundador del Instituto J. Craig Venter en San Diego, California, y sus colaboradores del instituto y del Instituto de Ciencia Translacional Scripps de La Jolla, también en California, enviaron la saliva de cinco individuos—no han hecho público quiénes son—a23andme y Navigenics, dos de las mayores compañías online de pruebas de ADN y ambas basadas en el área de la Bahía de San Francisco. En equipo de Venter analizó y comparó los resultados para ver si los sitios proporcionaban información consistente.

El equipo comparó los cinco grupos de resultados de ADN ante el riesgo de desarrollar 13 enfermedades, incluyendo el cáncer de colon, el lupus, la diabetes de tipo 2 y el síndrome de piernas inquietas.

Los resultados están publicados con fecha de hoy en un comentario de la revista Nature, junto a unas sugerencias acerca de cómo mejorar las pruebas genéticas como producto dirigido directamente al consumidor.

El grupo de Venter encontró que los datos en crudo de la secuenciación genética que proporcionaron cada una de las compañías era consistente casi a un 100 por cien. Es decir, de entre los 500.000 a 1.000.000 de marcadores genéticos que se testaron en cada persona, las As, Cs, Ts y las Gs eran casi exactamente las mismas.

El modo en que los sitios de tests genéticos interpretaban los datos era menos consistente. Cada uno de ellos utilizó estudios pertenecientes a la literatura científica que con anterioridad han llevado a cabo escaneados entre poblaciones humanas de marcadores de ADN asociados con factores de riesgo para poder predecir si una persona acabará falleciendo debido a una enfermedad en particular. Una persona puede tener, por así decirlo, un 30 por ciento de incremento de riesgo para la diabetes de tipo 2 si posee una versión particular del marcador genético relevante.

Para las siete enfermedades analizadas por los investigadores, sólo alrededor de la mitad de los factores de riesgo provistos por 23andme y Navigenics estaban de acuerdo en los cinco pacientes. Por ejemplo, para el lupus y la diabetes de tipo 2, tres de los cinco sujetos recibieron resultados que entraban en conflicto entre sí.

Tratando de ir un poco más lejos, los investigadores descubrieron que algunos de los factores de riesgo individuales eran sorprendentemente distintos. Para la psoriasis, 23andme reportó un factor de riesgo de 4.02 (cuatro veces mayor) para un individuo, mientras que Navigenics reportó sólo un 1,25 (un 25 por ciento mayor), una diferencia tres veces menor.

Durante mis propios experimentos, comparé los resultados entregados por varias páginas webs de pruebas genéticas: 23andme y Navigenics, así como deCodeme, con sede en Islandia. Los resultados relativos a un posible ataque al corazón produjeron tres niveles de riesgo generalmente distintos—un nivel alto según Navigenics, medio según 23andme, y bajo según deCodeme. Para otras enfermedades como la diabetes y la degeneración macular las contradicciones eran menos notorias.

Las diferencias están provocadas por dos razones principales: de debe a que las distintas compañías a veces utilizan distintos marcadores, así como combinaciones de marcadores, para determinar el riesgo general de contraer una enfermedad, y también a que los algoritmos que utilizan los sitios difieren en cuanto al peso que le dan a los distintos factores de riesgo para los distintos marcadores genéticos.

El estudio de Venter señala que, en algunos casos, las compañías definen de forma distinta el riesgo de enfermedad medio de la población. “Navigenics hace una diferencia entre el riesgo de enfermedad entre hombres  y mujeres (por ejemplo, los hombres tienen más tendencia a sufrir un ataque al corazón que las mujeres), mientras que 23andMe principalmente tiene en cuenta la edad (por ejemplo, la incidencia de artritis reumatoide aumenta con la edad),” señalan los autores en su estudio. “Esta ambigüedad en la definición de la ‘población’ subraya la precaución que hay que tener a la hora de interpretar los resultados de riesgo absoluto.”

Leer más en:

Fuente: TechnologyReview. Poniendo a prueba a las pruebas genéticas

This year, my 5 year-old son and I have passed many afternoons sitting on the living room rug learning to read.  While he ever so gradually learns to decode words, eg. “C-A-T”  sound by sound, letter by letter – I can’t help but marvel at the human brain and wonder what is going on inside.  In case you have forgotten, learning to read is hard – damn hard.  The act of linking sounds with letters and grouping letters into words and then words into meanings requires a lot of effort from the child  (and the parent to keep discomfort-averse child in one place). Recently, I asked him if he could spell words in pairs such as “MOB & MOD”, “CAD & CAB”, “REB & RED” etc., and, as he slowly sounded out each sound/letter, he informed me that “they are the same daddy“.  Hence, I realized that he was having trouble – not with the sound to letter correspondence, or the grouping of the letters, or the meaning, or handwriting – but rather – just hearing and discriminating the -B vs. -D sounds at the end of the word pairs.  Wow, OK, this was a much more basic aspect of literacy – just being able to hear the sounds clearly.  So this is the case, apparently, for many bright and enthusiastic children, who experience difficulty in learning to read.  Without the basic perceptual tools to hear “ba” as different from “da” or “pa” or “ta” – the typical schoolday is for naught.

With this in mind, the recent article, “Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response” [doi:10.1016/j.neuroimage.2009.02.045] caught my eye.  The research team of Jingyu Liu and colleagues asked healthy volunteers just to listen to a soundtrack of meaningless beeps, tones, whistles etc.  The participants typically would hear a long stretch of the same sound eg. “beep, beep, beep, beep” with a rare oddball “boop” interspersed at irregular intervals.  The subjects were instructed to simply press a button each time they heard an oddball stimulus.  Easy, right?  Click here to listen to an example of an “auditory oddball paradigm” (though not one from the Liu et al., paper).  Did you hear the oddball?  What was your brain doing? and what genes might contribute to the development of this perceptual ability?

The researchers sought to answer this question by screening 41 volunteers at 384 single nucleotide polymorphisms (SNPs) in 222 genes selected for their metabolic function in the brain.  The team used electroencephalogram recordings of brain activity to measure differences in activity for “boop” vs. “beep” type stimuli – specifically, at certain times before and after stimulus onset – described by the so-called N1, N2b, P3a, P3b component peaks in the event-related potentials waveforms.  Genotype data (coded as 1,0,-1 for aa, aA, AA) and EEG data were plugged into the team’s home-grown parallel independent components analysis (ICA) pipeline (generously provided freely here) and several positives were then evaluated for their relationships in biochemical signal transduction pathways (using the Ingenuity Pathway Analysis toolkit.  A very novel and sophisticated analytical method for certain!

The results showed that certain waveforms, localized to certain areas of the scalp were significantly associated with the perception of various oddball “boop”-like stimuli.  For example, the early and late P3 ERP components, located over the frontal midline and parieto-occipital areas, respectively, were associated with the perception of oddball stimuli.  Genetic analysis showed that several catecholaminergic SNPs such as rs1800545 and rs521674 (ADRA2A), rs6578993 and rs3842726 (TH) were associated with both the early and late P3 ERP component as well as other aspects of oddball detection.

Both of these genes are important in the synaptic function of noradrenergic and dopaminergic synapses. Tyrosine hydroxylase, in particular, is a rate-limiting enzyme in catecholamine synthesis.  Thus, the team has identified some very specific molecular processes that contribute to individual differences in perceptual ability.  In addition to the several other genes they identified, the team has provided a fantastic new method to begin to crack open the synaptic complexities of attention and learning.  See, I told you learning to read was hard!

It has been some years now that you can spit in a tube, put the tube in a box, mail the box, and get information about your genetic material in the screen of your computer in a matter of days. There are some companies that provide this service, such as 23andme, Navigenics, or deCODEme, and the cost fluctuates from about $200 to $1000 depending of the number of genetic markers (SNPs) that you get read. I must say that I have not tried this, but I am rather curious and probably will.

Today I read in Nature an informative “opinion” article [Ng et al., Nature 461 (2009) 724-726 (yes, I also find fascinating that Ng can be a surename, if it is not a typo)] in which a group of researchers of Craig Venter’s institute, including himself, analyze the different predictions about diseases risks coming from different companies. The study is small, 13 diseases, 5 individuals, 2 companies, but it produces some interesting conclusions, the most important one being that, whereas the genotyping techniques seem reliable (the companies agree in more than 97% of the SNPs), the link between genes and diseases is still poorly understood, thus producing significantly different predictions about disease risks in a number of cases.

As we all know, we are capable of anything! We are currently going through one of the most exciting times in Science right now where the technology we are using seems to be out of this world. We are learning new things everyday about ourselves mentally, physically,… genetically? What am I talking about…..well well, have you ever thought….what exactly am I made of and why am I different from everyone else? Let’s begin from the beggining, you are made of DNA (deoxyribonucleic acid) that is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).   Now, lets talk about GENES. A gene is the basic physical and functional unit of heredity. Genes that are made up of DNA, act as instructions to make molecules called proteins. Now lets talk about your GENOME. A genome is an organism’s complete set of DNA, this  includes all of its genes. The genome contains all of the information needed to build and maintain that organism. Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people.

Where am I going with this. In April of 2003, the Human Genome Project (HGP) was completed. To make a long story short there were to two projects an international public-sector (collected blood from female and sperm from male donors) and Celera Genomics private-sector project (few different genomes was mixed and processed for sequencing. Craig Venter, the lead scientitst has since acknowledged that his DNA was among those sequenced. Soooo its HIS sequence! My opinion and others…). Anyhow, since then many genomes have been sequenced from bacteria to mouse. Currently, there have been 5 genomes sequenced, including Ventor, Watson, Xinhua-Han (Chinese genome), Yaruba (African Genome), and some Korean dude (as my mentor names him).

Currently, one can pay for your genome to get sequenced by companies like 23andme,  deCOde Genetics, and Navigenetics for about $1,000-$3,000 or so. There have been criticism about these types of at home personal DNA testing. Several brave souls have gotten their genome sequenced by two of these methods and have found some similarities and more differences. Dr. George Church, a professor of genetics at Harvard Medical School is running a Personal Genome Project. Its mission is to “encourage the development of personal genomics technology and practices that: are effective, informative, and responsible,yield identifiable and improvable benefits at manageable levels of rik , and roadly available for the good of the general public.” Their goal is to enroll 100,000 informed participants from the general public, focusing on technology, science, ELSI (ethical, legal, and social issues), health care, personal knowledge, and products. Currently, they have already sequenced the first 10 participants called the PGP-10.

This means YOU, yes, YOU, can get your personal genome sequenced!!!My question here is would YOU be interested? If you either had to pay for it or get it for free? Many people I asked have replied saying, o no way! Why…fears of getting your genetic information displayed publically, insurance companies finding out your at risk of diseases, your job finding out your at risk of diseases, your family finding out your at risk of diseases, or you finding out your at risk of diseases.

As a student of Genetics and this growing field of NextGen sequenceing and personalized medicine….Yee Haa, I totally would! I actually already submitted my name to the PGP as a participant. I am curious however as to how they are going use my information. Can you beleive how much info they are going to obtain!

My main point………..What questions would you ask?

Maybe some of these pertaining to diversity…………….why are we different, is it in our genes?, what genes may dictate race/ethnicity?, if we are of a certain race/ethnicity do we have genes that put us at a higher/lower risk for diseases?, does our race even matter?

OR Maybe these……..why am I short?, why can’t I run a marathon?, why don’t I like reading?, or why don’t I like onions?     

OR positive ones……why am I great at science?, why can I dance my tail off in rythm all night and not be tired?, why can I ask silly questions and be really loud and not be embarressed? 

All I do know is that we all are different in our own way. We can all accomplish our goals and conquer our dreams. Here at Mayo Clinic there are people from all over the world who work here, learn here, and live here. We are at the leading edge of science and we certainly are pushing forward. Currently, Mayo contains several NextGen Sequencers (i.e. Illumina) and are anxiously awaiting a SOLID system. As a graduate student you get to see these accomplishments in action and sometimes be a part of it. Me…I’d rather be apart of it!!                                                   Jess

In Robert Sapolsky’s book, “Why Zebras Don’t Get Ulcers“, he details a biological feedback system wherein psychological stress leads to the release of glucocorticoids that have beneficial effects in the near-term but negative effects (e.g. ulcers, depression, etc.) in the long-term.  The key to getting the near-term benefits and avoiding the long-term costs – is to be able to turn OFF the flow of glucocorticoids.  This is normally dependent on circuitry involving the frontal cortex and hippocampus, that allow individuals to reset their expectations and acknowledge that everything is OK again.  Here’s the catch (i.e. mother nature’s ironic sense of humor). These very glucocorticoids can initiate a kind of reorganization or ’shrinkage’ to the hippocampus  – and this can disable, or undermine the ability of the hippocampus to turn OFF the flow of glucocorticoids.  Yes, that’s right, the very switch that turns OFF glucocorticoid flow is disabled by exposure to glucocorticoids!  Can you imagine what happens when that switch (hippocampus) get progressively more disabled?  Your ability to turn OFF glucocorticoids gets progressively worse and the negative effects of stress become more and more difficult to cope with.

Sounds depressing.  Indeed it is, and there are many findings of reduced hippocampal volume in various depressive illnesses.  The complex problem at hand, then, is how to reverse the runaway-train-like (depression leads to glucocorticoids which leads to smaller hippocampus which leads to more depression) effects of stress and depression?

One new avenue of research has been focused on the ability of the hippocampus to normally produce new cells – neurogenesis – throughout life.  Might such cells be useful in reversing hippocampal remodeling (shrinkage)?  If so, what molecules or genes might be targeted to drive this process in a treatment setting?

The recent paper by Joffe and colleagues, “Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness” [doi: 10.1002/hbm.20592] offers some key insights.  They examined 467 healthy participants of the Brain Resource International Database (a personalized medicine company with a focus on brain health) using personality tests, structural brain imaging and genotyping for an A-to-G variation (valine-to-methionine) polymorphism in the BDNF gene.  They report that lower volume of the hippocampus was associated with higher scores of neuroticism (worriers) – but, this negative relationship was not found in all people – just those who carry the A- or methionine-allele.  Thus, those individuals who carry the G/G (valine/valine) genotype of BDNF may be somewhat more protected from the negative (hippocampal remodeling) effects of psychological stress.  Interestingly, the BDNF gene seems to play a role in brain repair!  So perhaps this neuro-biochemical pathway can be explored to further therapeutic benefit.  Exciting!!

By the way, the reason zebras don’t get ulcers, is because their life revolves around a lot of short term stressors (mainly hungry lions) where the glucocorticoid-stress system works wonderfully to keep them alive.  Its only homo sapiens who has enough long-term memory to sit around in front of the TV and incessantly fret about the mortgage, the neighbors, the 401K etc., who have the capacity to bring down all the negative, toxic effects of chronic glucocorticoids exposure upon themselves. My 23andMe profile shows that I am a G/G valine/valine … does this mean I’m free to worry more?  Now I’m worried.  More on BDNF here.

If there is no proper genomic education in medical school, how can we expect medical professionals to be able to answer the genomic test related questions of their patients? There is still a solution (actually the easiest one is valuable post-graduate education). Let’s give them genomic tests and let them see themselves what kind of results they can receive. 23andMe now offers discounted genome scans to clinicians. Excerpts from a Times Online interview with Anne Wojcicki, co-founder of 23andme.

“Clearly we need to engage with physicians to help them to understand this information,” she said. “One of the things we’ve talked about is we’d love to get physicians comfortable with their own genomes first, have them understand what does it mean, explore the data, see what does it look like, and then go to work with their patients.

“I think that’s probably the way to do it. Physicians should be genotyped. We are talking about ways we could potentially do that. It’s important for physicians to understand what the experience is like; 23andMe is going to start putting more effort into educational material.”

Daniel MacArthur also mentioned the strange new outfit of the co-founders.Though, as I’ve previously reported, Linda Avey is leaving 23andMe.

(Via Genetic Future)

À tous ceux que cela intéresserait, voici le résultat de mon analyse génétique chez 23 And Me à propos de mes origines profondes, c’est à dire les grandes zones où mes ancêtres vivaient il y plusieurs millénaires de celà et comment leurs migrations s’inscrivent dans les grands mouvements de population qui ont façonné la répartition géographique des êtres humains sur Terre.

La capture d’écran ci-dessous concerne une analyse globale de mon génome (où pratiquement tous mes ancêtres ont laissé une trace) mettant en évidence les différents grands groupes raciaux dont je suis composé :

Les proportions rapportées ne m’ont globalement pas surpris.

En effet, je sais qu’une de mes arrière-arrière-grand-mère (sur 16 aïeux de ce niveau) était vietnamienne. Encore plus lointainement, une de mes (accrochez-vous !) arrière-arrière-arrière-grand-mère (1 sur 32) était thaïlandaise. Soit, une teneur probable en gènes asiatiques de 3/32, c’est à dire une prédiction médiane de 9,5% environ.

L’écart entre ce pourcentage et l’estimation de 23 And Me provient du fait qu’en réalité ma part génétique asiatique pouvait varier entre 0 et 50%, 3/32 étant la valeur médiane des probabilités, compte tenu de quoi une estimation de 6% paraît plausible.

Je remarque en outre que, si des racines asiatiques étaient attendues du côté de mon père, des traces asiatiques ont aussi été trouvées du côté de ma mère. Même infinitésimales, ces traces sont pour l’instant un petit mystère.

Une autre analyse permet de révéler des informations plus précises par la détermination des haplogroupes du chromosome Y (ADN-Y) et des haplogroupes de l’ADN mitochondrial (ADN mt). Pour simplifier les choses à mon propre niveau de compréhension, disons que ces groupes ADN-Y et ADN mt représentent les groupes qui m’ont été transmis de père en fils sur des centaines de générations, et des mères à leurs enfants génération après génération. Les mutations génétiques altérant le matériel génétique originel sont en effet des marqueurs permettant de distinguer des groupes, des sous-groupes, etc. et leurs évolutions.

Le groupe auquel ma lignée paternelle appartient est le R1b1b2a1a2f. À partir de ce que j’ai pu trouver sur internet, voici l’histoire (compatible avec ce que j’en attendais, ma lignée paternelle m’amenant dans la Manche) que ce groupe raconte :

Il y a environ 60.000 ans, le plus récent ancêtre patrilinéaire commun à tous les humains serait né en Afrique dans la région de l’Ouganda et du Kenya. Son haplogroupe était A. Une première série de mutations parmi les descendants de cet Adam créèrent, il y a environ 50.000 ans, l’haplogroupe B, puis le E, puis le C. À cette époque, les représentants de l’haplogroupe C se sont installés en Éthiopie, un peu plus au nord-est du bassin originel.

Environ 45.000 ans avant notre ère, des mutations de l’ADN-Y eurent à nouveau lieu et un représentant de l’haplogroupe C créa un nouvel haplogroupe, le F. Ce groupe effectua une migration très importante depuis l’Afrique de l’est jusqu’à la Mésopotamie. Des descendants d’individus appartenant à ce groupe mutèrent en K (40.000 ans), puis en P (35.000 ans), et enfin en R (30.000 ans), tout en se déplaçant vers le nord-est.

L’haplogroupe R1 est né en Asie centrale (entre la Mer Caspienne et l’Hindou Kouch), et se développa en R1b puis R1b1 dans la partie nord du Moyen Orient pendant la période glacière (25.000 ans). Les peuplades R1b ont probablement migré vers le nord de l’Anatolie et de l’autre côté du Caucase lors des balbutiements du Néolithique, où le chromosome Y évolua encore pour devenir R1b1b (12.000 ans).

R1b1b2 est vraisemblablement apparu lors de la culture de Maykop (entre 5.000 et 8.000 ans). C’était une culture néolithique avancée de fermiers et de pasteurs, et une des premières à développer la métallurgie, et par conséquent les armes en bronze. Coincés entre deux mers et le Caucase, le peuple de Maykop faisait probablement du commerce intensif autour de la Mer Noire.

R1b1b2 serait arrivée en Europe centrale il y a 4.300 ans d’ici, remontant le Danube à partir des côtes de la Mer Noire. Cela correspond au vide archéologique sur l’ancien territoire de Maykop, ce qui laisse penser que la migration doit avoir été massive, peut-être à cause de pressions d’autres peuples indo-européens au nord. Il pourrait y avoir eu plusieurs vagues successives de la Mer Noire vers le Danube, mais la plus importante a dû avoir lieu entre 2500 avant J.-C. (fin de la culture Maykop) et 2300 avant J.-C.

Ce peuple R1b proto-italo-celto-germanique s’installa au nord des Alpes vers 2300 avant J.-C., et d’après la propagation des cultures de l’Age du Bronze, atteint la péninsule ibérique vers 2250 avant J.C., la Grande-Bretagne vers 2100 avant J.-C. et l’Irlande vers 2000 avant J.-C. C’est vraisemblablement à cette époque que le sous-groupe R1b1b2a1a2f arriva dans les îles britanniques, en provenance du sud de l’Allemagne.

Sources : j’ai utilisé la carte proposée par Family Tree DNA et j’ai recopié des passages de pages du site Eupedia, notamment ici. Les cartes que vous trouverez à cette page permettent aussi de bien visualiser ces différentes migrations.

Mon haplogroupe maternel est H7, groupe qui semble être assez rare et sur lequel je ne dispose que de très peu d’informations. Voici l’histoire que la lecture de Wikipedia m’a permis de dégager :

NB : les haplogroupes mitochondriaux peuvent avoir le même nom que des haplogroupes Y mais qu’ils n’ont en fait aucun rapport entre eux.

L’Ève mitochondriale, c’est-à-dire le dernier ancêtre féminin commun à tous les humains, serait née il y a 150.000 ans dans la région de l’Éthiopie, du Kenya ou de la Tanzanie. Des mutations génétiques ont eu lieu et les groupes L1-6, puis L2-6, puis L2′3′4′6, puis L3′4′6, puis enfin L3′4 sont apparus successivement, avant que l’haplogroupe mitochondrial L3 n’apparaisse , il y entre 84.000 et 104.000 ans en Afrique de l’Est. Ce groupe L3 est important parce qu’il est l’haplogroupe dont tous les humains non-africains proviennent par leur filiation maternelle.

Viennent ensuite les mutations de L3 qui ont créé l’haplogroupe N il y a environ 70.000 ans. Les chercheurs ne semblent pas d’accord entre eux sur le lieu de naissance de cet haplogroupe : Asie ou Afrique de l’Est. Ce qui semble acquis cependant est que le groupe mutant suivant, l’haplogroupe R, serait né il y a 65.000 ans en Asie du Sud ou du Sud-Ouest. Viennent ensuite les mutations amenant au groupe R0 en Asie, il y a de celà entre 25.000 et 55.000 ans, celles créant le groupe HV (entre 25.000 et 30.000 de nous au Proche-Orient ou dans le Caucase), puis enfin celles engendrant le groupe H, il y a environ 25.000 ans au Moyen-Orient ou en Asie du Sud-Ouest.

C’est quelque peu frustrant, mais je n’ai pas pu trouver beaucoup d’informations sur la suite de cette succession de mutations : l’haplogroupe mitochondrial H7 vient à la suite du groupe H, mais pour l’instant sa géographie comme son époque d’émergence semblent inconnues.

Bien sûr, les connaissances scientifiques sur le sujet ne cessent de remettre en cause ce que l’on prend pour acquis et de nouvelles découvertes ne manqueront pas de modifier ou de simplement préciser ces résultats.

23 And Me propose un service innovant pour toute personne curieuse de ses origines, mais aussi pour tout individu intéressé, dans une démarche de prévention, par les informations d’ordre médical que son génome peut révéler. Je n’en ai pas parlé dans ce post mais cette partie de l’analyse de 23 And Me est aussi particulièrement prometteuse.

Je me suis aussi inscrit sur le site de l’entreprise texane Family Tree DNA qui propose un service plus poussé en matière de généalogie génétique. J’envoie demain mes échantillons de salive et d’ici quelques semaines, je pourrai ici-même partager mon expérience avec cette entreprise.

J’espère y trouver de nouvelles informations généalogiques, notamment grâce à la fonction de Family Tree DNA permettant d’identifier des cousins lointains, mais je suis aussi motivé par ma volonté de contribuer à la recherche en généalogie génétique : en participant à des projets proposés par Family Tree DNA, je pourrai à ma mesure aider les chercheurs à mieux comprendre les migrations anciennes.

It’s been several weeks now since I started working at 23andMe, a personal genomics company located in Mountain View, CA. Perhaps not coincidentally, it’s also been several weeks since I last blogged. The transition hasn’t been difficult, but it did take some getting used to, mentally and physically. I mean, leaving for work by 8:30am? Regular hours? Commuting??

Ok, so I really have nothing to complain about. 8:30 isn’t that early, and I could shave half an hour off each end of my commute if I didn’t choose to take advantage of bike-friendly roads, good weather, and a company-sponsored free train pass (OMG benefits!?). All in all, things are pretty much fantastic. The work environment is friendly, flexible, and laid-back; we have plenty of food and drink to keep us fueled throughout the day, and regular workouts/yoga if we need to get fired up or mellowed down (and to keep the “Free Food 15″ at bay). Plus, personal genomics is a super interesting and rapidly evolving industry, so there’s really never a dull moment.

So what is personal genomics, anyway? We’ve known for a while that genetics – the sequence of DNA inside our cells – plays an important role in our form and functioning. Many diseases are caused by changes in DNA (often in genes, parts of DNA that code for proteins) that alter the normal functioning of cells, though not all genetic differences lead to negative changes. (Genetics can also tell us about ancestry – who is related to whom and the history of populations – but I won’t be addressing that in this post.) Where it gets personal is when you apply it to individuals, such as when someone gets a genetic test to determine whether they have or are at risk of developing or passing on a particular disease. Where it gets genomics is when we use high-throughput technologies to do what is essentially thousands of genetics tests at once. Put them together, and you get personal genomics.

How do we know what genetic “pieces” correspond to what conditions or diseases? The general strategy is to compare the DNA of a whole bunch of individuals that have that condition (cases) to a whole bunch of individuals that don’t (controls). As long as both groups are similar save for their case-control status, any significant genetic differences between them should have something to do with that condition. We call this a genetic association.

It turns out that there are millions of single locations in the human genome where the exact sequence of the DNA might differ between two people, and these places, called single nucleotide polymorphisms, or SNPs, can contribute to differences we can observe, such as whether you flush when you drink alcohol or how easily you put on weight. 23andMe personal genomics kit determines what your sequence is for a representative subset of SNPs. Many are already known to be associated with certain conditions, and new research is being done every day to uncover more and more of these associations.

So what exactly do I do at 23andMe? My official job title is “Scientist, Content Curation”. Curation, I’ve found, is not very familiar to most people. Most people probably know that there is such a thing as a museum curator, but might not know what they do. Hardly anyone has ever heard of scientific curation. (And I thought explaining what I was studying as a grad student was hard! Biomedical informatics, anyone?)

But it’s really not that complicated. The essence of curation is almost always the same: the selection, acquisition, and management of content. What that content is differs depending on the field – for example, an art curator might look for and organize artwork for exhibition in a gallery, while a curator in the “Ancient Civilizations” department of a museum may be in charge of acquiring, managing, and presenting archaeological artifacts.

In science, curation involves organization of scientific knowledge and data. An area where this has been especially important is the life sciences, as the amount of information being generated by high-throughput experiments, large-scale projects, and scholarly publishing has skyrocketed. In order to manage this information and render it useful to others, the field of biocuration was born. Any database that organizes scientific knowledge – UniProt (the Universal Protein resource), FlyBase (database for that very important model organism, Drosophila), PharmGKB (a database focused on how genes and drugs interact), etc – depends on curators to keep the information up to date and easy to use.

And so it is with 23andMe. The genetic testing kit is one part of the product, but the other part is information – what knowledge is there about associations between the SNPs on our platform and health traits or conditions? What does your particular data mean? The science is far from exhausted on this subject, and in order to stay up to date with the research, 23andMe spends a lot of effort on curating the scientific literature for new genetic associations and presenting the information on our website for our customers.

Day to day, this means that we keep track of papers recently published in scientific journals, skim through to find ones that may have promising findings, and then vet these more thoroughly to see if they pass our stringent scientific standards. If they do, we extract the bits of information we need and put the bits together in reports that will eventually become part of the content on the website. It’s a job that definitely benefits from an organized system and an eye for detail – as well as a sense of curiosity.

After three weeks on the job, I think I’m starting to get the hang of the day to day work. Since my work is even more directly tied to the literature than it was as a graduate student in academia, I’m also developing an enhanced awareness of issues surrounding scientific publishing – those related to standardization and metadata, publication bias towards positive results, and closed vs. open access. The hardest aspect of transitioning from academia to industry hasn’t been the regular schedule, or the work environment, or the work itself, it’s been getting used to being on the other side of the pay-wall of scientific journals.

But that’s a rant for another time.

Here are a few interesting publications, articles, updates and news about personalized genetics.

• The first issue of Medicine Studies containing such articles as From Utopia to Science: Challenges of Personalised Genomics Information for Health Management and Health Enhancement

• 22andme? (GenomeBoy): Linda Avey is leaving 23andMe

I’ve decided that I’d like to focus my efforts on an area that is personally significant and will continue to have a huge impact on our healthcare system–Alzheimer’s disease. Effective today, I’m leaving 23andMe and have begun making plans for the creation of a foundation dedicated to the study of this disorder.

• The Human Genre Project (Genetic Future): A collection of poems and short stories assembled into the set of human chromosomes.

• UK Genetics Group Issues ‘Principles’ for DTC Testing (GenomeWeb)

• Genetic Variation and Loss of Physiologic Complexity Are Associated With Mortality in 644 Trauma Patients (Annals of Surgery)

Conclusions: This first study to simultaneously examine autonomic nervous system genetics, the biomarker complexity, and mortality concludes: (1) ANS genetics and physiologic complexity are independently related to mortality; (2) Genetics and complexity add information over traditional acuity scoring (probability of survival); and (3) Simultaneous assessment of ANS physiology and genetics may yield novel research, diagnostic, and therapeutic opportunities in critical illness.

• Seven Reasons Why Home DNA Tests Are Hype (Genetics and Health): Very valid points by Grace Ibay.

• Next Up – Navigenics (Genome Alberta)

Three weeks ago Medcan started offering the Navigenics direct-to-consumer test coupled with a family history and a follow-up once the results are in. If you order the test directly from Navigenics you also get access to counsellors, but in a clinical setting the options to really expand and act on the relevant information become much greater.

According to Jill Davies only about 20% of those direct to Navigenics customers actually take the opportunity to follow up with the company and I found that somewhat surprising.

• Illumina Announces Delivery of the First Genome Through Its Individual Genome Sequencing Service

• My ‘non-human’ DNA: a cautionary tale (New Scientist): Blaine Bettinger found an error in the DNA profile of the deCODEme service.

The false profile seems to be the fault of a software bug.

No harm was done, but the incident serves as a cautionary tale for personalised medicine. As we move towards a future in which readouts from our genomes will routinely be queried by computer systems to help doctors make important clinical decisions, similar glitches could cause prescribing errors – with patients being given drugs at the wrong dose, drugs that won’t work, or ones that could even trigger serious side effects in people with a particular genetic make-up.

I do believe there is a place for online patient research in our health care system, despite my privacy phobia. I understand the concern of relying on patient-reported data, since we as a species love to present our “best selves” instead of the real ones, but I think the benefit to the group of afflicted is a great one.

These communities could also aim education programs at their members, training them to be better researchers of themselves, to thus, encourage the creation and collection of the cleanest data possible. Let us not forget that gentlemen scribbling down observations in notebooks about their immediate world was the method of many hallowed Great Scientists. You can find the full article I referenced below here.

Amy Farber quit law school and founded the LAM Treatment Alliance to raise money and connect a network of scientists around the world to research this mysterious disease, which destroys young women’s lungs, after she learned she had the rare and fatal disease.

To her dismay, she says, she encountered a cumbersome research system fraught with obstacles to collaboration and progress — one that failed to focus on patient needs.

She took her frustrations to Dr. George Demetri, a member of her organization’s advisory board (and a professor and cancer researcher at Harvard Medical School) and Frank Moss, director of the Massachusetts Institute of Technology Media Laboratory.

The output of the collaboration between her group and the Media Lab: LAMsight, a Web site that allows patients to report information about their health, then turns those reports into databases that can be mined for observations about the disease.

Advocates like Dr. Farber say that online communities have the potential to transform medical research — especially into rare diseases like hers that lack the number of patients needed for large-scale studies and rarely attract research financing from the drug industry. Also, she said, it empowers patients to contribute, ask questions and help lead the way to discoveries.

“Patients have been a tremendously underutilized resource,” she said.

Supporters of this model — sometimes called crowd-sourcing or open-source research — call it democratization of research and say they are pioneering new models that put patients in control of their data and build bridges between researchers, patients and their doctors. They say these methods are far cheaper and faster than traditional research, which has high start-up costs and relies heavily on clinicians.

Still, some experts are skeptical. Questions abound about how these sites will guarantee patient privacy; whether patients fully understand what it means to share their medical information online; whether private businesses should have to follow the same strict patient protection rules that govern most researchers; and the quality problems of user-generated data.

In June, the Belgian pharmaceutical company UCB announced a partnership to build an online epilepsy community with PatientsLikeMe, among the first private companies to develop a platform for data sharing by patients. PatientsLikeMe, based in Cambridge, has as members tens of thousands of patients who contribute detailed information about their diseases, drugs, doses and side effects.

Genetic companies have also taken up patient-driven research. The Silicon Valley company 23andMe, for example, started a program this summer called “Research Revolution.” People can buy a stripped-down version of 23andMe’s genetic service, which gives people DNA information on ancestry and risk for certain diseases, for $99 and then contribute their genetic data toward research into the disease of their choice.

The company plans to store the genetic profiles of thousands of people to use for research internally and in partnerships with other companies. “We call it research 2.0,” said Linda Avey, a founder of 23andMe. “It’s the Wikipedia approach versus Encyclopaedia Britannica approach.”

Private companies like 23andMe and PatientsLikeMe are not bound by the same patient protection rules that govern traditional medical researchers who receive federal financing. Company leaders say they have detailed patient privacy statements and ethics policies.

**PODCAST accompanies this post** In the brain, as in other aspects of life, timing is everything.  On an intuitive level, its pretty clear, that, since neurons have to work together in widely distributed networks, they have a lot of incentive to talk to each other in a rhythmic, organized way. Think of a choir that sings together vs. a cacophony of kids in a cafeteria – which would you rather have as your brain? A technical way of saying this could be, “Clustered bursting oscillations, with in-phase synchrony within each cluster, have been proposed as a binding mechanism. According to this idea, neurons that encode a particular stimulus feature synchronize in the same cluster.“  A less technical way of saying this was first uttered by Carla Shatz who said, “Neurons that fire together wire together” and “Neurons that fire apart wire apart“.  So it seems, that the control over neural timing and synchronicity – the rushing “in” of Na+ ions and rushing “out” of K+ ions that occur during cycles of depolarization and repolarization of an action potential take only a few milliseconds – is something that neurons would have tight control over.

With this premise in mind, it is fascinating to ponder some recent findings reported by Huffaker et al. in their research article, “A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia” [doi: 10.1038/nm.1962].  Here, the research team has identified a gene, KCNH2, that is both differentially expressed in brains of schizophrenia patients vs. healthy controls and that contains several SNP genetic variants (rs3800779, rs748693, rs1036145) that are associated with multiple different patient populations.  Furthermore, the team finds that the risk-associated SNPs are associated with greater expression of an isoform of KCNH2 – a kind of special isoform – one that is expressed in humans and other primates, but not in rodents (they show a frame-shift nucleotide change that renders their ATG start codon out of frame and their copy non-expressed).  Last I checked, primates and rodents shared a common ancestor many millenia ago. Very neat – since some have suggested that newer evolutionary innovations might still have some kinks that need to be worked out.

In any case, the research team shows that the 3 SNPs are associated with a variety of brain parameters such as hippocampal volume, hippocampal activity (declarative memory task) and activity in the dorsolateral prefrontal cortex (DLPFC). The main suggestion of how these variants in KCNH2 might lead to these brain changes and risk for schizophrenia comes from previous findings that mutations in this gene screw up the efflux of K+ ions during the repolarization phase of an action potential.  In the heart (where KCNH2 is also expressed) this has been shown to lead to a form of “long QT syndrome“.  Thus, the team explores this idea using primary neuronal cell cultures and confirms that greater expression of the primate isoform leads to non-adaptive, quickly deactivating, faster firing patterns, presumably due to the extra K+ channels. 

The authors hint that fast & extended spiking is – in the context of human cognition – is thought to be a good thing since its needed to allow the binding of multiple input streams.  However, in this case, the variants seem to have pushed the process to a non-adaptive extreme.  Perhaps there is a seed of an interesting evolutionary story here, since the innovation (longer, extended firing in the DLPFC) that allows humans to ponder so many ideas at the same time, may have some legacy non-adaptive genetic variation still floating around in the human lineage.  Just a speculative muse – but fun to consider in a blog post.

In any case, the team has substantiated a very plausible mechanism for how the genetic variants may give rise to the disorder.  A scientific tour-de-force if there ever was one.

On a personal note, I checked my 23andMe profile and found that while rs3800779 and rs748693 were not assayed, rs1036145 was, and I – boringly – am a middling G/A heterozygote.  In this article, the researchers find that the A/As showed smaller right-hippocampal grey matter volume, but the G/A were not different that the G/Gs.  During a declarative memory task, the GGs showed little or no change in hippocampal activity while the AA and GA group showed changes – but only in the left hippocampus.  In the N-back task (a working memory task), the AA’s showed more changes in brain activation in the right DLPFC compared to the GGs and GAs.

For further edification, here is a video showing the structure of the KCNH2-type K+ channel.  Marvel at the tiny pore that allows red K+ ions to leak through during the repolarization phase of an action potential.   **PODCAST accompanies this post**

Yesterday’s NOVA ScienceNOW program included a segment on direct-to-consumer genomics (H/T to GenomeWeb’s Daily Scan Blog).  The program was bullish on George Church’s Personal Genome Project; but it took a pretty dim view of the predictive value of current consumer technology.

The program was accessible and interesting, but it went overboard in making a cautionary point about current DTC genomics offerings.  It transitions directly from Neal deGrasse Tyson’s 23andMe results for heart disease and diabetes to Steven Pinker’s genomic scan, which showed that Pinker had “double the risk of baldness,” whereas Steven is anything but bald.  Well, sure, and the weather report yesterday said there was an 80% chance of rain but it didn’t rain.  That doesn’t mean I should stop checking weather reports, or even that I was stupid to pack an umbrella.  It’s just probabilities.  I guess I agree with the program in the sense that anyone who can’t spot that flaw shouldn’t be interpreting their own genomic data, but it seems like an oddly condescending way for them to make the point.

Kudos, though, for pointing out:

1. the gaps in the Genetic Information Nondiscrimination Act; and 
2. the low risk to tenured Harvard profs of revealing their sequence data, as they are likely shielded from many of the risks to other participants.

So very interesting….

Q & A with Anne Wojcicki, co-founder of the “personal genetics” company 23andMe.

Q. Have you had any situations where a person finds out they have relatively recent ancestors of a race that they were unaware of? If so, have any reacted badly?

A. We know that quite a few people find surprises about their ancestry through 23andMe’s service. One customer with extensive knowledge of his European paternal ancestry discovered that his maternal line traced to a Native American woman. He tracked down paper records that revealed a “mulatto woman” about seven generations back. Native American ancestry makes some sense given that his ancestry traces to the southern U.S. While he was excited about this new information, his 93-year-old mother was far less positive and remains skeptical! Quite a few African Americans have discovered that their paternal line traces to Europe. Although many African Americans may be aware that they have some European ancestry (the average is about 20 percent), some discover that close to 50 percent of their ancestry traces to Europe, and this can take some getting used to.

Q. As projects like yours and the HapMap uncover numerous instances of genetic differences between human groups or races, what is the responsibility of the genetics community when discussing innate differences between races, particularly when a large part of academia is convinced that there are no such differences?

A. A lot of the difficulty in talking about race has been a lack of agreement on what “race” means. In the past, the idea of pure races also included an ordering of certain races as inherently superior to others. We reject this idea absolutely. However, that doesn’t mean that there are no genetic differences between populations of different ancestral origin. A few of our features use the genome-wide data of reference populations from around the world to trace the origin of pieces of an individual’s genome. Some customers have complex patterns depending on where their ancestors originated. These reference populations aren’t “races”; they’re representative samples of peoples who have lived in a single place for a very long time and have thus accumulated different sets of genetic variants over time.

pointer to: Great Q&A on Freakonomics with 23andMe founder Anne Wojcicki. Nice overview of peoples’ concerns and interests in personal genomes.

Veteran Scienceroll readers may remember when 23andMe gave a presentation in Second Life at the Scifoo event organized by Jean-Claude Bradley and me. Click here to see the whole transcript.

Joanna Scott of Nature.com just published something interesting:

I’ve found this video on Eye on DNA. Anne Wojcicki, co-founder of 23andMe, talks about Research Revolution, a new project of them.

Jen S. McCabe from Health Management RX shared her genomic results through a nice video. It’s a smart way to present how such a direct-to-consumer genetic company works, but I’m not sure Jen should publish such data.

Here is how she collected the salive sample:

I got a free kit from Navigenics a few months ago, and I shared my experiences, but not the results.