Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Carter
Not being a medical professional I bow to your superior knowledge. I did mean sulfonamide as a class of drug. One other thing to say is that there are multiple ACE inhibitors/ARBa, and it is quite possible to get to the magic number of 21 with statins and ACE inhibitors/ARBs alone.
From reading the statin patent application it seems that a main portion of response/non-response for any class of drugs can be determined from a set of SNPs, and they then overlay this with other SNPs specific to individual drugs. This is logical given that a given class of drugs should conceivably share a common mechanism. It might also be the case that for some classes of drugs the variability in response in individual drugs is not as great as with other classes. Therefore, it is certainly possible that they could quickly move ahead on multiple fronts in development - even if the apparent lead time for such development based on work on statins seems to be relatively long.
At the end of the day I don't care what exactly is being tested at this stage, as long as they end up with classifiers that can be used for up to 21 drugs. It would be nice to know which ones have been worked on or are being worked on, but we will find out eventually soon as the clinical trial details are public domain. The mere fact that we have effective classifiers puts us a long way ahead of everybody else as (leaving aside things that determine genetic basis for an aspect of drug metabolism e.g. cytochrome P450) I am not aware of any classifiers on the market or at similar stages of development.
Cardiac drugs
There are two broad types that IMO are of interest to us here: cholesterol lowering (e.g. statins) and antihpertensives (blood pressure lowering agents). The latter includes diuretics, beta-blockers, ACE inhibitors, and calcium channel blockers.
Statins: Lipitor, Lescol, Lipostat, Zocor, Altocor, Pravachol, Crestor, Baycol
Ace inhibitors: Enalapril, Lisinopril, Quinapril, Ramipril
Diuretics: Mannitol, Acetazolamide, Sulfonamide, a Thiazide, Spironolactone
Beta-blockers: Atenolol, Metoprolol, Propranolol
Calcium channel blockers: Nifedipine, Diltiazem, Verapamil
You can see how they perhaps get up to around 20 drugs...
The 21 drugs will be 6-7 statins, x-y ace inhibitors, and something else by the looks of it. Will look at this later. We know what the 3 cancer drugs are.
OT When I was just a little girl,
I asked my mother, 'What will I be?'...
Bag8ger, que sera sera!
Did anyone see this?
http://www.ktiv.com/News/NewsDetail63.cfm?ID=26,7694
07/28/2004
New Information In Dead Baby Case
Norfolk police have more DNA information to help them search for the parents of a baby boy found floating in a Nebraska river in June.
Officials say the new profile suggests at least one of the baby's parents is Hispanic, and there is also an indication that Native American ancestry was present in the infant.
Police Chief Bill Mizner says the bio-geographical ancestry results mean African Americans can be eliminated as a possible parent.
While he says it's still like searching for a needle in a haystack, it is a step in the right direction. Mizner said they are still counting on the public for help with solving the case.
"We are hopeful someone who might have knowledge of a person who may fit this profile or could be a part of this profile, if they've not stepped forward, to step forward now and notify the police division," said Bill Mizner, Norfolk Police Chief.
The body of the infant was recovered from the Elkhorn River in downtown Norfolk on June 17th.
Mizner says they are still unsure how or where the baby was placed in the river.
Obviously I agree regarding the low percentages, which is common sense. The first article puts Bamshad firmly in our camp IMO. The second article (leaving aside the content) essentially lists the main players in this particular field. They are all names that have been discussed here previously. The main point is that the leading lights are either explicitly associated with the company or (increasingly) seem to be approaching the company to discuss collaboration. Looking at the second article, apart from Shriver and Kittles the main names mentioned are: Parra (Shriver collaborator), Bamshad (say no more), Fernandez (Shriver collaborator), Sturm (Frudakis collaborator lol), Collins-Schramm (one of Seldin's, both of them Shriver collaborators). The interesting question is where you work of course...
Get out of bed the wrong side this morning Mike? lol
I'm sure this one has been posted before, I know I read it somewhere, but just in case:
http://www.backintyme.com/Essay040608.htm
No date on this one that I can see, but Mike Tiernan was talking about Bamshad the other day.
http://www.genetics.utah.edu/news/sc6press25.htm
Genes 'group' people by ancestry
By Lois M. Collins
Deseret Morning News
Race is less valuable than using genetic variants to infer ancestry when it comes to biomedical research.
That's because the use of genetic polymorphisms, as the variants are called, sorts people into categories that are much more precise than classifying them by race, said Dr. Michael J. Bamshad, associate professor of pediatrics at the University of Utah School of Medicine. Although race can provide some useful information, it can be inadequate and even misleading when it comes to finding genetic links to disease.
Bamshad and science writer Steve E. Olson review the body of research available on the topic for the cover story of the December issue of Scientific American, titled "Does Race Exist?"
"Race is not as useful as other ways we have to sort people," said Bamshad. "There is information in race, but there is information in many other labels used to define populations. And we have better ways to sort people into groups."
Researchers would learn more by sorting people using genetic polymorphisms, he said, identifying both traits in common in groups and traits that are different.
"One of the ultimate goals is to be able to make inferences or predictions about health-related susceptibilities in individuals. To do that, we need to understand how genetic variation is distributed among different human groups," Bamshad said.
For example, people from Africa, Australian aborigines and folks from southern India bear a superficial resemblance because of skin pigmentation, but they are genetically quite different. The skin color is a trait that developed to protect them from the sun blazing overhead. And racial definitions vary worldwide. Someone "black" in the United States might be "white" in Brazil and "colored" in South Africa , where there are others classified as "black" and "white."
On the other hand, two groups who are similar genetically might have been exposed to different selective forces, so they appear to be more different than they are.
"Common notions of race do not always reflect a person's genetic background," they wrote.
The goal is to find biological relationships that will allow researchers to sort people into groups that offer telling information about them. Sorting is important to geneticists looking for underlying causes of disease. It can also be important in forensics, evolution, even understanding history, Bamshad said. Genetic markers are more accurate and informative.
Ideally, Bamshad said, a genetic polymorphism for sorting people into groups would always be found in one group and never in another. It doesn't happen. Instead, "there might be two types of markers, A and B, in one group and the same in another group. But A is found in 90 percent of those in the first group, but in only 40 percent of those in group 2. Using many polymorphisms like this, you can sort people into groups 1 and 2."
Polymorphisms play a role in individual susceptibility to AIDS, for instance. Some people, the article states, have a small deletion in both copies of a gene that encodes a particular cell-surface receptor, so they fail to produce those receptors on the surface of their cells. Most strains of the virus that causes AIDS bind to that receptor, so people who don't have it are resistant to the HIV-1 infection. That polymorphism is found almost solely in groups from northeastern Europe .
Other variations in that same receptor allow the infection but change the rate at which it leads to AIDS and death.
OT The owner of IP address 218.102.140.166 who resides in Santa Clara is in for a very nasty surprise if they persist in attempts to hack into my PC. You have been warned.
There it is in black and white (as opposed to color):
"Rick Sturm, a pigmentation genetics expert from the University of Queensland, Brisbane Australia, co-authored the survey. Sturm's laboratory and the laboratory of Rick Martin (Queensland Institute of Medical Research, Brisbane Australia), from which the Zhu, et. al. paper originated, contacted DNAPrint last year and the three groups have been collaborating since."
People may recall that Mark Shriver originally approached DNAP as well. The increasing collaboration with leading academics, and publication of findings based on the company's technology in peer reviewed scientific journals, IMO says all we need to know about "validation" of the technology.
I think they are probably looking at DNA based classifiers for some traits (e.g. height and weight, and some of the facial characteristics) - possibly in conjunction with Queensland University of Technology - and also using typical values for some facial features index figures based on admixture. In practice we will probably see multiple enhanced versions of this product, as individual traits or groups of traits are added to it. There will come a point though where a DNA sample will be entered into the process and a digitally produced color identikit picture will appear on a screen. How far are we away from that is not known. Another interesting question is what are the impediments to ubiquitous adoption of such tecnology by every law enforcement agency apart from cost? I do not think there are any.
Indeed, and if that is the case we could potentially see a significantly enhanced version of DNA Witness earlier than we might have previously supposed.
He was referring to admixture percentages.
What we don't know is at what stage of development all this stuff is. Given that Tony mentioned specific traits you would think that they are possibly familiar with them! Of course, they could be looking at specifying typical trait charateristics for the admixture concerned, rather than inferring these phenotypes from the genotypes. In a previous post I referred to some research where they were mentioned "average" measurements for the ethnic group concerned.
Here is apparently a video of Mark Shriver giving a talk at the Fourth Annual Short Course ojn Statistical Genetics for Obesity & Nutrition Researchers. I couldn't get it to run earlier.
http://www.soph.uab.edu/ssg_content.asp?id=1227
WGCU interview with Tony Frudakis from 19th July 2004
http://www.wgcu.org/listen/gulfcoast_live.asp
Some highlights:
They are not developing drugs yet but intend to.
The error rate of DNAWitness is 4-8% for any percentage measured.
They will use facial recognition software in conjunction with DNA Witness to construct digital sketches of suspects. Future traits to be covered by DNA Witness:
- Skin color
- Eye color
- Hair color
- Height
- Weight
- Nose shape
- Distance between eyes
- Distance between cheekbones
- Whether earlobes attached
- Longitude and latitude of face
- Depth of cranium
- Any unusual inherited traits e.g. skull shape
The interviewer referred to a paper that Tony has apparently written called "Pharmacogenomics: The Paradigm Shift". Not sure if, when, or in what journal this is to be published.
When asked about cardiac drug related classifier development, Tony mentioned that DNAP had concentrated on a number of types of drugs, and specifically mentioned ace inhibitors and statins.
When asked about ovarian cancer/chemotherapy confirmed that can predict taxol and carboplatin response (based on two genes) and said that they are in the later stages of validating ovanome and "discussing with various types of organizations mechanisms of getting this type of test used and accepted for compensation by insurance companies, etc."
Have a nice day all.
http://www.nus.edu.sg/nex/instructors.htm#shahi
Dr Gurinder Shahi
Dr. Gurinder Shahi is CEO of BioEnterprise Asia. He is currently a Visiting Scholar/Executive-in-Residence at the University of Southern California's Marshall School of Business. He received his MBBS and PhD from the National University of Singapore, and went on to obtain his MPH in international health policy and management from Harvard University. Gurinder is a leading expert on change leadership and management. He has worked with leading international organization and corporations including the Rockefeller Foundation and the United Nations Development Programme. Among other initiatives, he was closely involved with the effort to establish the International Vaccine Institute and the Asia-Pacific International Molecular Biology Network. He also played a key role in helping to establish Lynk Biotechnologies, one of Singapore's leading biotech companies. Dr. Shahi served as lead editor for "International Perspectives on Environment, Development and Health: Toward a Sustainable World" (Springer Publishing, New York, 1997). He recently wrote the highly acclaimed book, "BioBusiness in Asia : How Asia Can Capitalize on the Life Science Revolution" (Pearson Prentice Hall, 2004).
http://www.marshall.usc.edu/web/IBEARMBA.cfm?doc_id=6415
IBEAR hosted world-renowned bioscience expert Dr. Gurinder Shahi for 6 intense seminars April 7, 8 and 9th, 2004. Drawing a diverse audience of medical professionals from USC Keck School of Medicine; faculty, students and staff from the California Institute of Technology, graduate students in business, medicine and life sciences; plus seasoned bioscience industry executives, Dr. Shahi presented an overview of the exponential growth expected in the bioscience industry over the coming years.
Dr. Shahi’s latest book, "BioBusiness in Asia - How Asia Can Capitalize on the Life Science Revolution" is published by Prentice Hall [ISBN #0130620459].
Reviews of the book:
"A brilliant, candid, readable book - a well-organized and comprehensive tour d'horizon of biotechnology's possibilities in Asia. Through this meticulous effort, Gurinder Shahi emerges as both a scientific and economic seer of highest regard."
Carl Feldbaum, President, Biotechnology Industry Organization
"An astonishingly insightful and valuable book that comprehends the science, business and public policy issues that confront Asia as life science begins to drive national and regional economies. A must read for serious business, political and policy leaders in the region and internationally."
David Beier, former Life Science Policy Advisor to US President Clinton and Vice-President Gore
"Breathtaking! One-stop shopping for Asia (and global) "BioBusiness" insight and analysis – both broad and deep. A superb contribution to everyone, whether new to the topic or experienced, who is interested in Asia’s BioBusiness opportunities. A tour d’force!"
Prof Jack G. Lewis, Marshall School of Business, University of Southern California
As W2P showed, Rick Kittles is now at Ohio State:
http://www.cancergenetics.med.ohio-state.edu/2749.cfm
Mike, that is interesting. So we seem to have the following "groups":
Europeans: European Parental, US Caucasians, Continental Europeans
Asian Populations: Chinese, Japanese, South East Asian, South Asian and Pacific Islander
American Populations: Hispanic
African Populations: West African Parentals, African Parentals, North Africans, Puerto Ricans
European and Middle Eastern Populations: North African, Middle Eastern, Northern European, Ashkenazi Jewish, Mediterranean
We also seem to have some limited Amerind classification capability.
In the table they identify Irish, Greek, Italian and Mexican source populations; although it seems that there is not enough resolution in the test to differentiate these currently.
So, we seem to be moving from a 4 way classification (European, Sub Saharan African, Native American, East Asian) to a 20 (?) way classification (or 16-18 way if you go by the "groups" in the table at the bottom). Again, it is not entirely obvious what the "groups" are.
And of course: "These are actual ANCESTRYBYDNA 2.5 results..." so it does seem as if there is a gradual progression from 2.5 to 3.0 classification even though we are still ostensibly "only" using 175 markers. The number of groups also broadly corresponds with comments previously made by Richard Gabriel:
http://www.dnaprint.com/2003/pressreleases/Jul04ShareHolder.htm
We improved our consumer product ANCESTRYbyDNA™ and upgraded it from a 71-marker test to a 175-marker test. We intend to continue improving the product, its accuracy and its ability to scan a broader platform of genetic heritage. Our goal is to expand our current 4 categories of inherited genetic markers to 8 and possibly 16 categories.
Mark D. Shriver received his Ph.D. in biomedical sciences from the University of Texas Health Science Center in Houston, USA. In 1999, he moved to the Department of Anthropology at the Pennsylvania State University, USA, and is now Associate Professor of Anthropology and Genetics. His research focuses on human population genomics, particularly on its applications to admixture mapping of genes for common traits and diseases, and genomic scans for signatures of natural selection.
http://live.psu.edu/index.php?sec=vs&story=6900&pf=1
Following is a list of academic promotions for tenured and tenure-line faculty, effective July 1.
TO ASSOCIATE PROFESSOR
Mark D. Shriver, anthropology, College of the Liberal Arts
And neither is this new: the textbook is old news, and Mike Tiernan told us about the Nature Genetics article yesterday! lol. Of course the latter is a really big thing, despite what Messrs Shriver (also a recently promotee) and Kittles say about population groups...
OK, the digital photo library is not new of course:
http://www.dnaprint.com/2003/pressreleases/pr_05_02_03.htm
DNAPrint Launches Ancestry 2.0 Forensic Profiling Service and Immediately Impacts Several Criminal Investigations
May 2, 2003
"A precise inference of skin tone will require a specific genetic test, which the Company is working on, but to allow forensics customers the immediate ability to make inferences of physical characteristics from Ancestry 2.0 results, the Company intends to provide forensic customers next quarter with access to a database of several hundred digital photographs from individuals who have taken part in the Company's validation studies. The customer would query the database to retrieve photographs for every individual whose profile falls within a specified range, such as "80% European + 20% sub-Saharan African +/- 10%", Through inspection, the customer would gauge variation in physical appearance associated with that range."
However, the patent application has not been mentioned before to my recollection (but then again my memory is not what is was). The "mid-Atlantic customer" is interesting (must be Iceland). The other interesting thing is that we seem to be having more frequent PRs about this product line.
DNAPrint Upgrades DNAWitness(TM) 2.5; New Information Technology for Better Physical Profiling
Thursday July 22, 11:29 am ET
SARASOTA, Fla., July 22 /PRNewswire-FirstCall/ -- DNAPrint genomics (OTC Bulletin Board: DNAP - News; the "Company") announces today that it has upgraded its DNAWitness(TM) 2.5 product for physical profiling from DNA with a proprietary database designed to help investigators learn what their results say, or don't say, about physical appearance.
The DNAWitness(TM) 2.5 genome test allows forensics investigators to employ objective science, empiricism and statistical analysis in the reconstruction of a physical profile or "fuzzy photo" from DNA left at a crime scene. It employs the world's first molecular genetics test for the inference of BioGeographical Ancestry (BGA) admixture. For example, DNA at a crime scene may indicate that a person is of 90% East Asian, 10% European mix. BGA is obviously related to physical appearance, and individuals with fewer admixtures tend to have more accentuated anthropometric characteristics (those that vary from race to race). Investigators who obtain a result such as 100% East Asian typically have little difficulty interpreting the result, but investigators who, for example, obtain a result such as 70% European, 30% East Asian usually ask whether the person's physical appearance would reveal the East Asian admixture. Communicating how BGA relates to physical appearance is difficult to do with words in a scientific way, but the advance announced today is the first solution for this problem.
To project what a person may look like from knowledge of their DNA, DNAPrint has developed the DNAWitness(TM) 2.5 database of individual BGA admixture results. The database contains information on how individuals previously tested have self-defined in terms of ethnicity (called the "geopolitical" arm of the database) as well as their digital photographs. By querying the database using a specific BGA admixture result, investigators can see for themselves what the range of variability is corresponding to that result for various features, such as skin shade, hair texture, nose shape, epicanthal eye folding, etc. Whether or not, for example, individuals of 70% European, 30% East Asian admixture tend to show no East Asian features, would be apparent from the database query. Statistical tools soon to be added will allow investigators to use Analysis of Molecular Variance to determine whether there is a systematic difference in the expression of an anthropometric trait that can be measured from the photograph in one database sample set versus the international average, or versus another group. DNAPrint has already filed patent applications on the use of digital photograph databases and databases of biographical data with BioGeographical Ancestry admixture data.
Last week, the Company provided a mid-Atlantic customer access to this database for the first time; all DNAWitness(TM) 2.5 customers from today forward will enjoy its use.
About DNAPrint genomics, Inc.
DNAPrint genomics, Inc. uses proprietary human genome research methods to develop genomic-based services and products. The Company introduced AncestryByDNA in the consumer market and DNAWitness(TM) in the forensic market in 2003. DNAPrint is developing products in the pharmacogenomic market and has a disease gene discovery program. The Company is traded on the Nasdaq OTC Bulletin Board under the ticker symbol: DNAP. For more information about the company, please visit http://www.dnaprint.com.
All statements in this press release that are not historical are forward- looking statements within the meaning of Section 21E of the Securities Exchange Act as amended. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including, but not limited to, uncertainties relating to technologies, product development, manufacturing, market acceptance, cost and pricing of DNAPrint's products, dependence on collaborations and partners, regulatory approvals, competition, intellectual property of others, and patent protection and litigation. DNAPrint genomics, Inc. expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in DNAPrint's expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based.
Media and Press Contact
Richard Gabriel
DNAPrint genomics, Inc.
CEO/President
(941) 366-3400
Babe, yes I got it and could read it.
4titudinous usually finds these things first! lol
We knew it was coming:
Eye colour: portals into pigmentation genes and ancestry.
Sturm RA, Frudakis TN. Eye colour: portals into pigmentation genes and ancestry. Trends Genet. 2004 Aug;20(8):327-32.
Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.
Several recent papers have tried to address the genetic determination of eye colour via microsatellite linkage, testing of pigmentation candidate gene polymorphisms and the genome wide analysis of SNP markers that are informative for ancestry. These studies show that the OCA2 gene on chromosome 15 is the major determinant of brown and/or blue eye colour but also indicate that other loci will be involved in the broad range of hues seen in this trait in Europeans.
OT, yes, see previous post.
OT Miss Scarlet, yes, you are the only other person (apart from gunnerbe) who doesn't know what is going on! The rest of us spend most of out time swapping private messages about the hilarity of the whole situation. You do know that I am really spook don't you, and that it is frog who is W2P's brother (not ifida). Most of us are employed by Research Capital to spread Fear, Uncertainty and Doubt (except the ones who are employed by Big Pharma of course - but some of the lucky ones like Dickholder101 are employed by both). Did I mention that I was really Stephen O'Brien? The glorious day approaches when the "true longs" will recant their previous heresy and announce publicly that DNAP is truly headed for "de crapper". BTW, did you know that DragonEsquire REALLY is the Antichrist?
I'm amazed that you two still haven't figured it out. Did you see The Truman Show...
Miss Scarlet, that's OK. It is after all a matter of public record.
Sorry you look at it that way, but I understand how these things can appear. There was no personal slight intended. Maybe there was a reluctance to address the issue publicly previously, and perhaps there was a good reason(s) for that. I decided to address it today after it had been raised yet again, and the question was addressed explicitly to me and W2P.
One final observation on this subject. In the May 2004 10Q the following appears:
NOTE G- CONTINGENCIES
We are involved in certain legal action arising in the ordinary course of business. We are defending these proceedings. While it is not feasible to predict or determine the outcome of this matter, we do not anticipate that this matter will have a material adverse effect on our business or on our consolidated financial position or on our results of operations.
Now, you either believe this or you do not. If you do not then, on the same basis, you probably should not believe anything else in the 10Q (or 10K or any other communication such as a newsletter etc). I choose to believe what I read in black and white in an SEC filing. There is no ambiguity IMO - the company believes that these lawsuits are not material.
Yes I know for certain that is the case.
Yes, we do know all about the suit. It is a matter of public record (if you can drop by the Florida Circuit Court that is). It essentially involves a dispute about how George is to renumerated for a loan that he provided the company - i.e. in cash or stock. End of story.
Here's another admixture mapping study:
http://www.nationalmssociety.org/Research-Hafler3.asp
David A. Hafler, MD
Whitehead Institute for Biomedical Research Cambridge, MA
Region: Central New England Chapter
Award: Research Grant
Term/Amount: 4/1/04-3/31/07; $670,788
Funded by the NMSS Central New England chapter, in part by gifts from Barbara Palmer
“A whole genome admixture scan for the multiple sclerosis genes” Scanning for MS genes in genetic material from patients whose ancestry contain a mix of populations at high risk and at low risk for MS.
Although MS is not inherited directly, there appears to be a genetic predisposition to developing the disease. Evidence indicates that a single gene alone does not determine the risk of getting MS. Many separately inherited genes appear to contribute to MS susceptibility, making the search more complex. David A. Hafler, MD, is using a new and powerful technique called “admixture mapping” to identify MS genes.
As it relates to MS, admixture mapping involves studying the genetic basis of MS in populations with mixed racial ancestry. MS in African-Americans is clinically similar to that seen in European-Americans (Caucasians). However, African-Americans have only one-half the risk of developing MS when compared to those of European extraction. Continental Africans have an even lower rate of MS than African-Americans. These facts suggest that genetic susceptibility to MS in African-Americans may lie in the genetic material that might have been inherited from a European ancestor.
Dr. Hafler’s team is studying genetic material from 1000 African-Americans with MS, collected by Jorge Oksenberg, PhD, and Stephen Hauser, MD (University of California at San Francisco) with separate funding from National MS Society. They are identifying which parts are of European ancestry, and are looking for small overlapping regions that may contain MS genes.
This study should help to identify MS genes not only in African-Americans but will help to pinpoint MS susceptibility genes in the general population as well, and may provide targets for the development of new drugs for MS.
There's a coincidence because this lot are also working on admixture mapping and MS:
http://maths.dur.ac.uk/php/seminars.php3?series=MG&identifier=2302&parent_page=timetable
LMS Durham Symposium: Mathematical Genetics
Dr David Reich (Harvard Department of Genetics)
High density admixture mapping to find genes for complex disease and application to multiple sclerosis
Abstract:
(Joint work with N Patterson, N Hattangadi, MW Smith, SJ O’Brien, PD Jager, MJ Daly, D Altshuler, JR Oksenberg, SL Hauser and DA Hafler)
Admixture mapping is a powerful way, in principle, to carry out whole-genome scans for disease genes. The method in theory requires ~100 times fewer markers than whole-genome haplotype mapping, but should have similar statistical power to detect disease variants that differ strikingly in frequency across populations. The key idea of admixture mapping is that near a disease gene, patient populations descended from the recent mixing of two or more ethnic groups should have an increased probability of inheriting the alleles from the group with greater disease susceptibility. Since gene flow occurred recently (in African and Hispanic Americans in the past 20 generations), recombination has not had much time to act and linkage disequilibrium should extend many centimorgans.
Admixture mapping has never previously been used to identify a gene associated with a disease. One reason is that there was no high density map with large frequency differences across populations. Here we report 3 results suggesting that admixture mapping should soon be a practical method for mapping genes for complex disease in African Americans.
• We have generated a map of 2,154 SNPs with average frequency difference of 57% between Africans and Europeans. These were chosen from ~450,000 SNPs with known Africans and European frequencies, and revalidated in a new set of 378 samples to confirm their appropriateness for admixture mapping.
• We have developed methods that allow analysis of data from such a high density map. Applying the approach to two data sets we have collected in the laboratory, we show that strong admixture linkage disequilibrium extends, on average, 17 cM in African Americans. Power calculations show that ~2,000 markers in ~2,000 patients can provide high power to detect disease loci.
• Finally, we have applied whole-genome admixture mapping for the first time to a complex human disease (multiple sclerosis). We will report preliminary results from 756 SNPs genotyped in 712 cases and controls, which allow us to scan for admixture association.
Some recent papers:
Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O'Brien SJ, Reich D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet. 2004 May;74(5):1001-13. Epub 2004 Apr 14.
Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004 May;74(5):979-1000. Epub 2004 Apr 14.
Looks like Esteban Parra has some funding:
http://www.bbdc.org/fundingDesc/pilotfeasibility.htm
Dr. Esteban Parra - Construction of an admixture mapping panel to study type 2 diabetes. $30,000
Esteban has some experience in this area of course:
Relation of type 2 diabetes to individual admixture and candidate gene polymorphisms in the Hispanic-American population of San Luis Valley, Colorado
Esteban J Parra, Clive J Hoggart, Carolina Bonilla, Sonia Dios, Jill M Norris, Julie A Marshall, Richard F Hamman, Robert E Ferrell, Paul M McKeigue, and Mark D Shriver
(Letter to JMG)
Bonilla C, Shriver MD, Parra EJ, Jones A, Fernandez JR. Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city. Hum Genet. 2004 Jun;115(1):57-68. Epub 2004 Apr 30.
Moore LG, Shriver M, Bemis L, Hickler B, Wilson M, Brutsaert T, Parra E, Vargas E. Maternal adaptation to high-altitude pregnancy: an experiment of nature--a review. Placenta. 2004 Apr;25 Suppl A:S60-71.
Brutsaert TD, Parra E, Shriver M, Gamboa A, Palacios JA, Rivera M, Rodriguez I, Leon-Velarde F. Effects of birthplace and individual genetic admixture on lung volume and exercise phenotypes of Peruvian Quechua. Am J Phys Anthropol. 2004 Apr;123(4):390-8.
Bonilla C, Parra EJ, Pfaff CL, Dios S, Marshall JA, Hamman RF, Ferrell RE, Hoggart CL, McKeigue PM, Shriver MD. Admixture in the Hispanics of the San Luis Valley, Colorado, and its implications for complex trait gene mapping. Ann Hum Genet. 2004 Mar;68(Pt 2):139-53.
Fernandez JR, Shriver MD, Beasley TM, Rafla-Demetrious N, Parra E, Albu J, Nicklas B, Ryan AS, McKeigue PM, Hoggart CL, Weinsier RL, Allison DB. Association of African genetic admixture with resting metabolic rate and obesity among women. Obes Res. 2003 Jul;11(7):904-11.
Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG, McKeigue PM. Control of confounding of genetic associations in stratified populations. Am J Hum Genet. 2003 Jun;72(6):1492-1504.
Brutsaert TD, Parra EJ, Shriver MD, Gamboa A, Palacios JA, Rivera M, Rodriguez I, Leon-Velarde F. Spanish genetic admixture is associated with larger V(O2) max decrement from sea level to 4338 m in Peruvian Quechua. J Appl Physiol. 2003 Aug;95(2):519-28. Epub 2003 Apr 11.
Shriver MD, Parra EJ, Dios S, Bonilla C, Norton H, Jovel C, Pfaff C, Jones C, Massac A, Cameron N, Baron A, Jackson T, Argyropoulos G, Jin L, Hoggart CJ, McKeigue PM, Kittles RA. Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet. 2003 Apr;112(4):387-99. Epub 2003 Feb 11.
Molokhia M, Hoggart C, Patrick AL, Shriver M, Parra E, Ye J, Silman AJ, McKeigue PM. Relation of risk of systemic lupus erythematosus to west African admixture in a Caribbean population. Hum Genet. 2003 Mar;112(3):310-8. Epub 2003 Jan 24.
Wagner JK, Parra EJ, L Norton H, Jovel C, Shriver MD. Skin responses to ultraviolet radiation: effects of constitutive pigmentation, sex, and ancestry. Pigment Cell Res. 2002 Oct;15(5):385-90.
Wagner JK, Jovel C, Norton HL, Parra EJ, Shriver MD. Comparing quantitative measures of erythema, pigmentation and skin response using reflectometry. Pigment Cell Res. 2002 Oct;15(5):379-84.
Ye J, Parra EJ, Sosnoski DM, Hiester K, Underhill PA, Shriver MD. Melting curve SNP (McSNP) genotyping: a useful approach for diallelic genotyping in forensic science. J Forensic Sci. 2002 May;47(3):593-600.
Wu H, Wang H, Li H, Oshuaakey J, Xiao F, Ke Y, Xu H, Xiao J, Lu D, Parra E, Shriver M, Xiong M, Barton SA, Hewett-Emmett D, Liu W, Ji L. Skin reflectance in the Han Chinese and Tibetan populations. Hum Biol. 2001 Jun;73(3):461-6.
McKeigue PM, Carpenter JR, Parra EJ, Shriver MD. Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations. Ann Hum Genet. 2000 Mar;64(Pt 2):171-86.
Akey JM, Sosnoski D, Parra E, Dios S, Hiester K, Su B, Bonilla C, Jin L, Shriver MD. Melting curve analysis of SNPs (McSNP): a gel-free and inexpensive approach for SNP genotyping. Biotechniques. 2001 Feb;30(2):358-62, 364, 366-7.
Parra EJ, Kittles RA, Argyropoulos G, Pfaff CL, Hiester K, Bonilla C, Sylvester N, Parrish-Gause D, Garvey WT, Jin L, McKeigue PM, Kamboh MI, Ferrell RE, Pollitzer WS, Shriver MD. Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina. Am J Phys Anthropol. 2001 Jan;114(1):18-29.
Pfaff CL, Parra EJ, Bonilla C, Hiester K, McKeigue PM, Kamboh MI, Hutchinson RG, Ferrell RE, Boerwinkle E, Shriver MD. Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium. Am J Hum Genet. 2001 Jan;68(1):198-207. Epub 2000 Dec 07.
Shriver MD, Parra EJ. Comparison of narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry. Am J Phys Anthropol. 2000 May;112(1):17-27.
Parra E, Saha N, Soemantri AG, McGarvey ST, Hundrieser J, Shriver MD, Deka R. Genetic variation at 9 autosomal microsatellite loci in Asian and Pacific populations. Hum Biol. 1999 Oct;71(5):757-79.
Parra E, Shriver MD, Soemantri A, McGarvey ST, Hundrieser J, Saha N, Deka R. Analysis of five Y-specific microsatellite loci in Asian and Pacific populations. Am J Phys Anthropol. 1999 Sep;110(1):1-16.
Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R, Forrester T, Allison DB, Deka R, Ferrell RE, Shriver MD. Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet. 1998 Dec;63(6):1839-51.
Remember Lonnie Bookbinder?
http://www.sema4usa.com/Company/events/LifeSciences2002.htm
Semaphore Dedicates Life Sciences Diligence Practice
Firm emphasizes and expands Technology and Sciences diligence to Bio/Pharma markets.
(Boston- London- Zurich) Sema4, Inc. (Semaphore) announces the expansion of its Technology Diligence practice. Stating that Semaphore clients are experiencing greater activity in the Life Sciences markets, Semaphore CEO Mark S. DiSalvo states “We thought it appropriate to greater emphasize the skills and resources we have to provide assurance and Independent Verification and Validation in the Life Sciences and Bio/Pharma markets, especially since our clients are asking us to perform this level of assurance.”
This dedicated Life Sciences business practice was created to provide visibility and clarity to the decision-making process. “It facilitates informed judgments on risk and opportunity. The Life Sciences are often subject to misunderstanding, misapplication and misrepresentation,” said DiSalvo. DiSalvo explained that this confusion has a deleterious effect on productivity in even the most business savvy environments. Semaphore research has discovered that when Technology Diligence is applied prior to, or in concert with, a funding event it provides appropriate and necessary discipline to the judgment process. The result allows for increased confidence in the decision contemplated and executed. Research confirms that Bio/Pharma projects such as drug development are nearly always over budget, behind schedule, or are abandoned completely. Facts are that the FDA approves less than 2% of the drug pipeline. Those that do receive approval often are not commercially successful. Semaphore services in this space include Clinical Trial review, FDA compliance and certification process monitoring, proof of science concept, and acquisition target validation.
The firm has significantly expanded its resources globally in the Life Sciences space. Richard Gabriel former CEO of Calix Corporation is the point person for the firm as head of Life Sciences diligence services practice. “I am delighted to join the quality team represented by Semaphore. Its skills providing real-world diligence from Emerging Technologies to Enterprise Software to Life Sciences are legendary,” he added. His team includes: Hector Gomez, MD, Ph.D, former CEO of Transcend Therapeutics, Inc. and Lonnie Bookbinder, Ph.D, an experienced large Pharma executive. “The strength of this dedicated team will offer our clients the clearest direction and best assurance of success possible. We bring hard science and business savvy to the table every day,” Gabriel added.
For any new investors, Richard Gabriel is the DNAP CEO/President and Hector Gomez is the DNAP CHasirman and Chief Medical Officer, hence the interest in what Dr. Bookbinder gets up to. We always found it difficult to find out much about Lonnie (leaving aside Lewis & Clark expedition and Ribi Group disgruntled investor related bits and pieces). Here's something I came across today though:
http://66.102.9.104/search?q=cache:_UE3ehBGgqUJ:www.efeckta.com/company.php3+%22lonnie+bookbinder%22...
Lonnie Bookbinder, PhD – Vice President, Marketing
Dr. Bookbinder has over 30 years experience in the biopharmaceutical industry. Lonnie has a BS in Biological Sciences, and has done post-grad work in Pharmacology, Clinical Research, Toxicology, earning an MBA and Ph.D. in Business Management. He has served as Chief Operating Officer, CellPath, a start-up drug discovery company; Vice-President Corporate Development, at Ribi ImmunoChem, a cancer vaccine development company; Vice-President Corporate Development, at Nycomed-Salutar, a drug development company. In addition, he served as Director, OEM agreements at In-Vivo Business Unit, Immunomedics, and key account executive at Lederle Labs.
This is from a cached page for this site, the current page does not have Lonnie suggesting that he is perhaps no longer with the company concerned. It does provide a bit more background though.
We do indeed want "a well mannered discussion that attempts to increase the level of understanding of the science". This will be eoucouraged. Personal attacks will be removed as per the IHUB terms of service agreement. Let's move on.