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W2P, if you would like to, feel free...
Did anybody ever wonder if there was a connection between messrs Chakraborty and Rao? I gave one previously (their mentor). Here is another:
Rao DC, Chakraborty R. Detection of inbreeding and efficiency of mating bioassay. Am J Hum Genet. 1974 Sep;26(5):578-80.
Rao DC, Chakraborty R. The generalized Wright's model and population structure with special reference to the ABO blood group system. Am J Hum Genet. 1974 Jul;26(4):444-53.
Chakraborty R, Rao DC. Detection of the inbreeding coefficient from ABO blood-group data. Am J Hum Genet. 1972 May;24(3):352-4.
Another presentation by Zach Gaskin
CHI's 6th Biannual DNA Forensics meeting
June 24-25, 2004
http://www.healthtech.com/2004/fdx/index.ASP
Creating a Higher Throughput Laboratory
Dr. Thomas Scholl, Myriad Genetics, Inc.
Dr. Stephen Sherry, NCBI/NIH
Dr. James W. Schumm, The Bode Technology Group
Dr. Alex M. Garvin, Bureco, AG
Mrs. Gabriela Saldanha, Promega Corporation
Mr. Mark Kavlick, FBI
Dr. Phillip Danielson, University of Denver
Dr. Zach Gaskin, DNAPrint Genomics, Inc.
http://www.healthtech.com/2004/fdx/day2.asp
12:15 DNA Witness
Mr. Zach Gaskin, Technical Director of Forensic Genomics, DNAPrint Genomics, Inc.
Five murdered and sexually assaulted women from around the Baton Rouge area were found to have a common foreign DNA donor through STR DNA analysis. The genetic profile of the donor from the crime scene specimens could not be found in a database. With no suspects, the Louisiana Task Force set out to dragnet suspects from the local community. Eyewitness accounts of a Caucasian male acting suspicious near the crime scenes focused the efforts of the task force in what would later prove to be the wrong direction. In February 2003, the Louisiana State Police Crime Lab contracted the services for DNA WITNESS testing after the dragnet DNA testing produced no “hits” from the more than 700 individuals tested. Our results indicated the killer to be 85% Sub-Saharan African and 15% Native American, and two months after receiving this information, the task force had an African American male in custody that matched the STR profile found at each crime scene. This SNP-based DNA test for the determination of an individual’s Biogeographical Ancestry (BGA) has been utilized for genealogy enthusiasts, adopted individuals, and persons wanting to prove Native American affiliation. This presentation will provide information on the scientific foundation of the test and how it can and should be applied in modern forensics.
bag8ger, not an easy one to answer simply. The way I would look at it is that it is not necessary to understand the complete process(es) involved in the trait determination under consideration, as long as you know markers which can determine qualitatively (if not quantitatively) the trait concerned.
Sometimes it seems that knowing the details of pathways is not always necessary. Here is the summary from the Statin patent application:
The results of this SNP screen are shown in Table 9-13. From Table 9-13 it is evident that many different genes impact variable Statin response. For most of the outcomes, there were SNPs from at least four different genes associated. It is also clear that the gene compliments are highly unique for each end point and each gene. The GSTs (GSTM1, GSTT2, GSTA2) were quite strongly associated with LIPITOR.TM. response, linked with LDL, TC and SGOT outcome, but not ZOCOR.TM. response. The NAT2 gene was only found to be relevant for ZOCOR.TM. response, and only had impact on the TC lowering effect of the drug, not the LDL lowering effect. CYP2C8 was an important determinant for both LIPITOR.TM. and ZOCOR.TM., for the former, impacting both TC and SGOT outcome. Of significant interest, no SNPs, or only weakly associated SNPs in the HMGCS1, MVK or HMGCR gene were identified, though we previously described HMGCR haplotypes associated with response. Usually, the ability to identify associations at the level of the SNP indicates the gene contribution towards response is relatively strong compared to genes with associations only apparent at the level of the haplotype. The HMGCS 1, MVK and HMGCR genes are part of the cholesterol synthesis pathway inhibited by Statins, yet our results suggest that most of Statin variable response is attributed by xenobiotic metabolism gene sequences, not target pathway sequences. The associations we have described earlier in this application therefore are a function of haplotype, not SNP sequences. With these haplotypes, and SNPs from genes below, a linear or quadratic discriminate classifier (as we have described elsewhere, (T. Frudakis, U.S. patent application Ser. No. 10/156,995, filed May 28, 2002), Fru fdakis et al., J. Forensic Science, (2002); Frudakis 2002a) is possible to predict each outcome.
Here are two more submssions to the FDA regarding their pharmacogenomic data submission guidelines (for the sake of completeness I will also list the Johnson & Johson one discussed previously):
Johnson & Johnson:
http://www.fda.gov/ohrms/dockets/dailys/04/jan04/012204/03D-0497_emc-000001-02.pdf
NIH:
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03D-0497_emc-000009-01.pdf
Japan Pharmaceutical Manufacturers Association:
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03D-0497_emc-000003-01.pdf
W2P, the patent applications are fascinating to read, if a bit technical. There are always a couple of very interesting insights amongst the details. It seems that a common theme is the role played by genes that were not previously supposed to be associated with the trait under consideration. It is also interesting that this work looks as if it will make a contribution to the elucidation of human evolutionary history, and as Mark Shriver says to understand where you are going you have to know where you have come from.
OT bag8ger, I wonder if Arch has any experience of that!
Frog, while it is true that there is a clear inference that the competitive advantage is directly related to the amount of time that the information could be kept from publication, you cannot suppose that the eventual presentation of the details will necessarily eliminate the competitive advantage. Notwithstanding the fact that at least some of the "competitive advantage" relates to the elapsed time between the filing of the provisional/utility patent applications and the details becoming publicly visible, there are questions about how usable the details would be to the competition – especially in terms of being able to utilize the details to perform a method which would not clearly violate the patent. There is also the issue that the company has patented all of the components of the ADMIXMAP platform, and we should therefore not be solely concerned with the AIMs patent, even though it is potentially the most important.
It is, as you infer from Tony Frudakis’s statement, fair to assume that the competition can extract meaningful and helpful information from the patent. A key issue here is to what extent can they use that information "outside of the protection provided by the patent"? We are hampered somewhat in that we do not ourselves know the details of this particular patent, or know with certainty the "phenomena" that the company believes it has uniquely discovered (i.e. we may suppose, but do not yet know, that these are solely concerned with population structure).
In the absence of being able to provide a comprehensive answer to this point, let me reproduce some relevant material that at least gives us some context – and which I base my own opinions on.
From the December 9, 2002 press release (“DNAPrint Launches Revolutionary Pan-Genome Screening Platform Based on Ancestral Admixture Mapping”):
http://www.dnaprint.com/2003/pressreleases/pr_12_09_02.htm
DNAPrint genomics, Inc. (OTC Bulletin Board: DNAP - News; the "Company"), unveiled a new whole-genome screening platform (ADMIXMAP) that promises to rapidly change the landscape of disease and drug response gene hunting. The new platform is revolutionary because it represents the first yet developed for cost-effective whole-genome scanning in large, heterogeneous populations. It taps into sequence differences among the world's various continental population groups to increase the power and efficiency of pan-genome disease gene screening.
ADMIXMAP will allow DNAPrint to identify new disease and drug response genes 10 times faster and 1,000-times less expensively than others who use existing methods. Dr. Tony Frudakis, CEO, informally announced the introduction of ADMIXMAP to attendees at the invitation-only IBM Life Science Solution Developer Conference in Boca Raton, FL, and proclaimed the Company's intent to partner collaborative services based on the platform to pharma, biotech and academia.
The development of ADMIXMAP was a culmination of years of research into population genomics structure and human ancestry conducted with Dr. Mark Shriver of the Pennsylvania State University. The primary focus of the work was to create an original type of human genome map based on validated and characterized Ancestry Informative Markers. snAIMs are Single Nucleotide Polymorphsims (SNPs) of significant allele frequency differences between the world's various continental population groups; prior to DNAPrint's work, such a map had not existed. This map is combined with other compositions and new, highly specialized analytical algorithms to constitute the ADMIXMAP platform. The platform functions by allowing a fine appreciation of population genomics structure relevant for solving complex human conditions, and it is based on a process called Mapping by Admixture Linkage Disequilibrium (MALD) or Admixture Mapping (AM).
DNA exists in a block like state, and hypothesis-free genome screens aim to inspect each of several hundred thousand of these blocks for sequence correlation with disease or drug response. A genome-wide study usually queries hundreds of genomes. Because each genotype costs about $0.50 and hundreds of thousands of genotypes need be created per genome, a typical genome study costs several tens of millions of dollars.
On the other hand, Mapping by Admixture Linkage Disequilibrium (MALD) or Admixture Mapping (AM) takes advantage of the fact that in recently admixed populations (i.e. Hispanics or African Americans, among many others), the block-like structure of DNA extends for MegaBases rather than kilobases (Chakraborty and Weiss, 1988; Stephens et al., 1994, McKeigue 1998, McKeigue et al., 2000). Because the DNA is made of a relatively small number of very large blocks, pan-genome coverage can be obtained with as few as 1,500 markers at a cost of only $1-2K per sample or a couple hundred thousand dollars per study.
MALD and AM can only be accomplished using Ancestry Informative Markers (AIMs) and to its knowledge, the Company is the only to yet mine the human genome to produce a pan-genome map of validated snAIMs. In addition to a validated AIM map, the MALD/AM methods also require the determination of individual ancestry admixture proportions and DNAPrint was the first to reduce the determination of individual admixture proportions using AIMs to commercial practice (see www.ancestrybydna.com). As a result, DNAPrint believes it is the only company in the world capable of practicing the MALD and AM methods.
"The single largest problem drug and diagnostics developers currently face is the cost associated with genotyping," said Dr. Matt Thomas, DNAPrint's Chief Molecular Biologist. "Due to this cost, most whole-genome research today is restricted to isolated, homogeneous populations, which can limit the general applicability of the results obtained."
"In part, the human genome was sequenced to help us get away from a restrictive focus on homogeneous, isolated populations for drug and diagnostics design," said Zack Gaskin, DNAPrint's Chief Technician. "Because ADMIXMAP is the first platform to enable cost-effective whole genome scans in heterogeneous populations, we expect it to have a profound impact on genomics- based drug and diagnostics design and we consider its development to represent an important milestone in human genome research."
DNAPrint intends to partner this new platform with biotech, pharma and academia seeking to identify new drug targets and diagnostic tests. Using this model, partners would fund the work and the Company would retain a share of the intellectual property produced. DNAPrint hopes to use the method with partners to discover hundreds or even thousands of disease genes and to acquire a significant stake in the future of genomics-based medicine. Given the magnitude of drug and diagnostics royalties, relatively few of the discovered genes need be developed as drug targets or diagnostic tests to render the endeavor a success.
Here is a news article from November 21, 2003 that people might not have seen previously that covers the same ground more succinctly:
http://www.separationsnow.com/basehtml/SepH/1,1353,6-1-4-1-0-news_detail-0-816,00.html
Genome Screening Platform Based on Ancestral Mapping
Last Updated: 21 November 2003 (Medinews.com)
A new platform that allows whole-genome scanning in large heterogeneous populations will help researchers identify new disease and drug response genes much faster and less expensively.
The platform, called Admixmap, is based on years of research into population genomics structure and human ancestry conducted with Dr. Mark Shriver of Pennsylvania State University (University Park, USA). The focus of the research was to create an original type of human genome map based on validated and characterized ancestry informative markers, or snAIMS, which are single nucleotide polymorphisms (SNPs) of significant allele frequency differences among the worlds various continental population groups. This map is combined with other compositions and highly specialized analytical algorithms to constitute Admixmap. The platform is based on a process called mapping by admixture linkage disequilibrium (MALD) or admixture mapping (am).
Admixmap is the product of DNAPrint Genomics, Inc. (Sarasota, FL, USA). The company says by using Admixmap, it can identify new disease and drug response genes 10 times faster and 1,000 times less expensively than existing methods. DNAPrint intends to partner this new platform with biotechnology, pharmaceutical, and academic organizations to identify new drug targets and diagnostic tests.
Because Admixmap is the first platform to enable cost-effective whole genome scans in heterogeneous populations, we expect it to have a profound impact on genomics-based drug and diagnostics design and we consider its development to represent an important milestone in human genome research.
From the December 2002 Newsletter:
http://www.dnaprint.com/dnanewsletter.pdf
"The first to identify a disease causing or drug response gene variant owns it, and each variant connection can only be discovered once. Once discovered and patented, the new owner controls their use in the therapeutic and diagnostic markets. Because there are only so many genes for any disease, this means the new owner also controls a significant fraction of the therapeutic and diagnostic market for the disease itself."
"The first company to build a "disease gene discovery platform" to overcome these limitations could be the first to discover hundreds or even thousands of disease genes."
"DNAPrint exercises a virtual monopoly on this method, not only for the present because we are the only ones with the resources to perform the method, but by virtue of our patent, which effectively precludes others from performing the method efficiently."
So it would appear that ADMIXMAP (not to be willfully confused with any other things that have a similar nomenclature) provides the company with significant advantages in terms of the identification of new disease and drug response genes allowing them to develop new drug targets and diagnostic tests (not forgetting disease predisposition in addition).
Will the AIMs patent help DNAP corner the market on practical genome screening, as Tony Frudakis believes? Will other companies be able to utilize information contained in the patents in such a manner that they can circumvent our patent(s)? What has the company done with the platform in the intervening period and what else has they potentially discovered? How many other patent applications related to e.g. drug response classifiers are in preparation or have been submitted?
We do not know the answers to these questions and await developments. Like W2P though, I believe that the details of the AIMs patent will provide more insight into at least some of these questions. In the meantime, and considering the fact that nobody else seems to have developed a complex trait classifier (and we seem to have developed at least five), I am inclined to believe that the ADMIXMAP platform and the patents currently provide and will continue to provide a significant competitive advantage.
OT Give me strength...
Here's another DNA Ancestry database, although this one is concerned with X and Y chromosome testing:
http://tv.ksl.com/index.php?nid=5&sid=77920
New Genealogy Database Focused on DNA
Feb. 27, 2004
Carole Mikita Reporting
The world of science has entered the search for family history, a first of its kind in the world, developed here in Utah. Sorenson Molecular Genealogy Foundation will announce Monday the most comprehensive way for many to find their genealogy through DNA.
Utah is THE place in the world to do genetic research. That's the unwritten motto of a foundation created to link scientific data and family trees. The idea came from billionaire businessman, James Sorenson; his goal, he says, is simply to bring people together.
James LeVoy Sorenson, Sorenson Molecular Genealogy Foundation: "It connects you in a unique way to many, many people out there. Many, many."
The database has two components. First: build -- there are 40,000 names in there now but the foundation wants more, your DNA, your genealogy.
To add to the database you order a packet online. In that packet is a consent form, a genealogy chart and a little bottle of mouthwash that you swish in your mouth for 45 seconds. Put it in a plastic bag and everything you put into a self-addressed stamped envelope to Sorenson Foundation.
Scott R. Woodward, Ph.D., Chief Scientific Officer: "They are receiving nothing back personally. This is altruistic. This is completely beneficial to, hopefully, the whole family of man. I'm amazed that we have had so many people willing to do that."
The second is the search, which will require a test, probably costing $200. The company will send you your 'Y" chromosome signature. You would enter those codes into the database, then you get information on pedigree charts.
Scott R. Woodward, Ph.D., Chief Scientific Officer: "If we can tease that information out of our genes, about who are parents are and who are grandparents are, we can convert that into genealogical information, and that's the purpose of this database."
For now, it's set up to trace male ancestors; within months, the maternal side. And the database, at this point, only goes back to the 1400s but it is a start.
Jim Sorenson: "It's a powerful thing. We need to connect."
The foundation is looking for people who want to share their genealogy. That website will be available Monday.
There is a video at this site:
http://tv.ksl.com/index.php?nid=39&sid=77934
Utah Company Introduces New D.N.A. Ancestry Database
Feb. 27, 2004
The world of science has entered the search for family history, and a Utah company is at the forefront. On Monday, Sorenson Molecular Genealogy Foundation will make an interactive website available to the public. The first-of-its-kind ancestry database is both a place to give information and get it. Billionaire businessman, James Sorenson developed the idea to as he says, bring humanity together.
James LeVoy Sorenson/Sorenson Molecular Genealogy Foundation: "WE'RE TOSSED TO AND FRO SO MUCH MORE NOW ON A GLOBAL SENSE, BY TRAGEDIES, OF FEAR, HATE, ENVY. HOW CAN WE BALANCE THAT, HOW CAN WE MAKE THAT MORE OF A LOVE, PEACE, JOY AND FELLOWSHIP?"
Here's a link to the Sorenson Molecular Genealogy Foundation:
http://www.smgf.org/
From this we can see that they are using Relative Genetics for all of their laboratory processing needs. That might have something to do with this:
http://www.sorensoncompanies.com/sorenson_genomics.html
"Sorenson Genomics is a world-class genomics laboratory and a global industry leader in high-throughput DNA analysis. Using advanced techniques and automated systems for processing large DNA extraction and purification, DNA genotyping, and DNA sequencing projects. Sorenson Genomics has two marketing arms, GeneTree and Relative Genetics. GeneTree provides innovative DNA analysis for paternity, grand-parentage, and cousin testing, while Relative Genetics assists genealogists in validating their genealogies and identifying family lines thorough DNA testing on the Y-chromosome and genetic family studies."
We can also see that there are three (unnamed) people on their Scientific Advisory Board.
Here is a website about Scott R. Woodward, their CSO:
http://cpms.byu.edu/cancerresearch/html/scott_r._woodward.html
And, absolutetly nothing to do with the Mormons (it says so in the FAQ).
Frog, although you addressed your post to W2P allow me to provide some input in the interim. I think that a key document for people to be familiar with in this context is the Consulting Agreement with Mark Shriver that was an attachment to the 10QSB filed on August 14, 2002:
http://www.sec.gov/Archives/edgar/data/1127354/000107087602000071/shriverconsultagmt.htm
A number of things are apparent from this document. Here are a few pertinent quotes:
This Consulting Contract Agreement (this "Agreement") is made and entered into as of June 12, 2002
DNAPRINT is the patent owner of certain SNP markers and methods, and desires to collaborate with CONSULTANT to develop a kit product that could be used to infer Ancestry Admixture Ratios in individual human beings.
CONSULTANT is the inventor of certain compositions and methods useful for determining Ancestry Admixture Ratios in individual human beings. CONSULTANT is also the owner of certain DNA samples collected from individuals of various
ancestries, and of certain rights therein. CONSULTANT wishes to commercialize his compositions and methods.
To create a panel of Ancestry Informative Markers (AIMs) that can be accurately, specifically and sensitively used to infer the relative ancestral admixture ratios in individuals, with respect to a list of target ancestral groups. Definitions of adequate accuracy, specifically, sensitivity, and target groups will be determined jointly by DNAPRINT and CONSULTANT.
CONSULTANT will provide DNAPRINT with DNA samples. DNAPRINT will score genotypes for a panel of Ancestry Informative Markers (AIMs) agreed to by both parties.
Data will be made for all DNAPRINT and CONSULTANT AIMs together on a single panel of individuals from several target populations...
DNAPRINT and CONSULTANT will define a minimum and optimum set of AIMs necessary for achieving product goals.
DNAPRINT will modify CONSULTANTS existing computer software programs with the intent of commercializing them to achieve the goals of the project.
5.1 CONSULTANT agrees and understands that any and all data, software improvements, methods, compositions and commercial rights are the property of DNAPRINT, and that CONSULTANT acquires no rights therein and that it can use DNAPRINT data, including any Documentation, only for legitimate scientific research as previously approved by DNAPRINT, and for no other purpose whatsoever.
5.2 Privacy. Genotyping data is the property of DNAPRINT, and CONSULTANT may not sell, loan, disclose or present DNAPRINT data in any manner whatsoever, unless requested by or agreed to by DNAPRINT.
End of Consulting Agreement quotes
From the July 10, 2002 press release ("DNAPrint Inks Research and Product Development Alliance With Penn State University"):
http://www.dnaprint.com/pr_7_10.htm
Researchers from both institutions will team to complete admixture mapping and candidate genome screens to identify the complex genetic determinants of variable human skin pigmentation, tanning/burn response and melanoma risk. A primary goal of the work will be to confirm and extend encouraging results each has previously obtained from preliminary genome screens. The research will be part of a larger effort at DNAPrint to develop a panel of genomics- based tests for the inference of physical traits from DNA, but it could ultimately lead to the development of new, specific drugs for various pigmentation-related diseases and UV-response traits.
The impetus for the alliance was DNAPrint's recent success in developing complex genetics classifiers for the inference of human iris and hair color. "DNAPrint's work in the pigmentation field is innovative, and their results to date are compelling," said Mark Shriver, Assistant Professor of Anthropology and Genetics at PSU. "We have been conducting skin pigmentation research for some time at PSU, but we suggested an alliance because we felt a team effort would be the most efficient means by which to finally solve this fascinating puzzle."
Under the terms of the agreement, DNAPrint gains access to DNA and data from over 1,000 reflectometry-qualified specimens of multiple ancestral backgrounds. In addition, DNAPrint obtains exclusive and unlimited rights to exploit previous pigmentation results and analytical methods developed in Dr. Shriver's laboratory. Both groups will fund the research and DNAPrint will pay PSU a minority share of revenues derived from products that result from the collaboration.
End of PR quote
Now I know that willful misinterpretation is possible, however it seems to me that there are some clear implications from the text that I have highlighted from the two sources above.
Whose markers are we talking about when we talk about AIMs? Clearly work had been undertaken by BOTH parties prior to the agreement. DNAP had successfully developed complex classifiers BEFORE the agreement with PSU. Most telling is the statement that DNAP is the PATENT OWNER of certain SNP markers. I personally think that DNAP and PSU pooled their respective AIMs. How about this from the August 20, 2002 press release ("DNAPrint Files Patent to Protect 2,425 SNPs Linked to Drug Response"):
http://www.dnaprint.com/pr_8_20.htm
"DNAPrint has previously compiled a candidate gene database of several thousand validated drug metabolism and drug target gene SNPs -- collectively known as the "PHENOME" SNP database. However, the new SNPs claimed in the present patent application were identified from a different, more systematic screen of the entire human genome. The sequence of each is useful for explaining variation in drug response to differing extents, depending on the drug, and the Company's data suggests that most are likely linked to genes in the human genome previously not known to be of pharmacological relevance. As such, DNAPrint believes it is the first to claim markers of this type and elucidate the potential of this new subset of the variable human genome as specifically relevant for predicting drug response."
When did this more systematic screen occur? We do not know but I would imagine it was not in the period from July 10, 2002 to August 20, 2002.
What is the significance of the dates? The consulting agreement is dated June 12, 2002. This would have had to have been negotiated and reviewed by both DNAP’s and PSU’s legal advisors. This process did not take place overnight. What do you think the elapsed time concerned was? Six months? Twelve months?
What about the dates of the patents applications? Here they are for the US patent applications for Ovanome and Statnome:
Ovanome
60/334,310 Filed 28 November, 2001
60/410,363 Filed 11 September 2002
Statnome
60/301,867 Filed 29 June, 2001
60/310,783 Filed 7 August, 2001
60/322,478 Filed 13 September, 2001
What can we infer? The Ovanome patent application may well have benefited from Mark Shriver’s AIMs (if it needed to). We can not necessarily say the same about the Statnome patent application, but we do know that DNAP had developed complex classifiers previously without Mark Shriver’s AIMs in any case.
Now let’s go back to your questions. I will put comments in italics after them (I have taken the liberty of correcting your spelling lol).
-Given the history of Shriver's arrival and the subsequent and very immediate patent application bearing both names, is it fair to assume that the new 'advantage' in developing pharmacological classifiers, was a fairly sudden departure from the previously developed technology that bore the previously announced development projects Statinome and Ovanome?
Not necessarily as the above demonstrates. I think that the collaboration may well have enabled subsequent update of the two projects (and patents).
-Since the competitive advantage had a limited timespan (until the USPTO published the application) can we assume that that advantage has been exploited vigorously and the scientific team has developed new classifiers in the interim?
I am not sure if you meant to use the past tense here. I do not personally think that the competitive advantage ends with the publication of the application (or the patent itself). In that case what they have or have not been doing in the interim is not directly relevant to this point IMO.
-As the advantage post dates the Statinome and Ovanome classifiers and the competitive advantage was necessarily short lived, does this explain the apparent 'back burner' status of these previously highly touted products? The limited resources of the company would necessarily have to be devoted to developing products based on the short lived competitive advantage.
Again, the advantage does not necessarily post date the classifiers or that the competitive advantage was short lived. I also do not think that this explains the “back burner” status. We can assume that work on the classifiers has not been as rigorous as might have been the case with additional funding and without the intervening concentration on Ancestry. However, it is clear that work has continued in part on the two products.
-Now that the application has been published and the 'headstart' has played out, can we expect to hear about all the new classifiers that have been developed during the protected timeframe?
See above.
-If there have been no new products developed in the interim due to monetary or resource limitations, what advantage still exists now that the 'cat is out of the bag' so to speak?
The advantage conferred by the patent application and, in due course, by the patent itself.
W2P, yes it must be the same patent (US: 60/467,613 - Methods and Markers for Accurate Estimates of Human Ancestry). I did wonder myself whether or not the statement: "the company will refrain from presenting details of the discovery until the findings are published by the US Patent and Trademark Office" could be taken to infer that the patent is about to be/has been granted by the US Patent Office? It has been 18 months since the application was made...
Yes, it came from the IPDL, which has undergone a bit of a facelift in the last week or two (amongst other things they merged two formerly separate searches). At the moment there is only the front page. The front page database is updated to 26 February, whereas the full text database is updated to 12 February. Whether this means we will get the full text to this patent in two weeks time I do not know, as the lag in updates may not be the same as the lag between the front page and full text updates for a given patent of course. There is no corresponding entry on either the US Patent Office or Espacenet databases.
Incidentally, for the benefit of others, the IPDL search page is here:
http://www.wipo.int/ipdl/en/search/pct/search-adv.jsp
You have to use a keyword search parameter in the query box. I usually use the term "in/frudakis".
Interesting point about the dates. I think that we can comfortably infer that Mark Shriver was involved with the company some time before July 2002.
I agree the details on this one will be very interesting.
Those are good questions you ended your post with! Worth repeating. Does this qualify as the company having been mentioned along side of Shriver as a contributor to his research? Are these Paul McKeigue's markers, or ours? Just curious...I get confused you know. You and me both Mike!
From the PR:
"A review has been commissioned and is now underway to determine the direction of a proposed joint venture in the near future involving both entities."
One obvious question is does the proposed joint venture involve only ADOT and GMED, or one or more third parties in addition?
GMED sometimes follow up with a short piece in the St Louis Business Journal which provides more details.
http://www.bizjournals.com/stlouis/
Possible JV involving ADOT and GMED
http://home.businesswire.com/portal/index.jsp?epi-content=GENERIC&newsId=20040227005088&news...
February 27, 2004 07:30 AM US Eastern Timezone
Advanced Optics Electronics Moves to Enhance Display Technology; Biomoda Scheduled for SB-2 Completion & poss JV with Genomed Inc.
ALBUQUERQUE, N.M.--(BUSINESS WIRE)--Feb. 27, 2004--Indesign (Indianapolis, Ind.) has been retained by Advanced Optics Electronics Inc. (OTC BB: ADOT) to increase the capabilities of ADOT's advanced sign development technology. Focus on enhancement will be directed to light sensitivity and video synchronicity.
Biomoda Inc. (30% directly and indirectly held by ADOT) has filed an additional patent relating to assay and protocol tests. Biomoda's pending SB-2 is slated for completion shortly after the company files its 10K for 2003.
Advanced Optics Electronics Inc.'s 2003 10K is scheduled to be filed within the next 30 days. The company recently confirmed that outstanding debt continues to be greatly reduced. Net worth will reflect this fact and other positive developments.
Advanced Optics currently holds approximately 16% of Biomoda Inc. as a direct investment and over 20%(a) of Genomed Inc., a publicly traded biotech company. A review has been commissioned and is now underway to determine the direction of a proposed joint venture in the near future involving both entities.
(a) 14.2% as of 2/27/04; 20.3% after 3/15/04
Advanced Optics Electronics Inc. is a technology company based in Albuquerque, N.M. The company maintains an R&D facility and manufacturing plant, and is engaged in building large-scale flat panel displays utilizing its patented and patent pending technology.
In addition to the core business of ADOT, the company has made a strategic technology-oriented investment in Biomoda Inc. Biomoda Inc. is a company that holds patents and patents pending domestically and internationally for the early detection of lung cancer. ADOT currently holds directly and indirectly 30% of Biomoda Inc.
New WIPO Patent Application
WIPO Number: WO 2004/016768
Title: COMPOSITIONS AND METHODS FOR INFERRING ANCESTRY
WIPO application published 26 February 2004
First published in US 19 August 2002 (revised 2 May 2003)
Ancestry informative marker (AIMs) polynucleotides that contain a single nucleotide polymorphism or that contain an insertion or deletion, are provided, as are methods of using panels of the AIMs to draw an inference as to a trait of an individual. The trait can be, for example, biogeographical ancestry, a pigmentation trait, responsiveness to a drug, or susceptibility to a disease. Also provided are methods of determining the proportional ancestry of an individual. Reagents and kits also are provided.
This one is assigned to DNAPrint Genomics, and both Tony Frudakis and Mark Shriver are given as applicants.
That and the typical inertia/resistance to change/lack of vision/self interest prevalent in the medical community.
But he did mention Japan! You are right though - you would expect an existing international alliance to crop up somewhere in the interview (even given any time constraints). It seems that several parties are being a bit coy at the moment...
That's very interesting that he would take the CTO role, and says a lot about the perception of the potential of DNA Phenomics. Let's not forget that Senecio are involved in NIH projects. Note also the use of the phrase "the growing number of alliances" by Jerry Wicks. Not to mention the fact that DNA Phenomics essentialy regard Senecio as their IT division! lol
A couple of rough quotes from the WallSt.net interview with Dave Moskowitz:
http://www.wallst.net/
In the next 12 months GMED wants to construct a 10-20K SNP chip and use it to "solve" one disease as a proof of concept. The following year they want to use the chip to "run through" the 250 most common diseases and corner the market on disease causing genes.
In 3-5 years GMED think they will be the major genomics based disease management company in the US and Japan. They should be the starting point of collaborations with drug companies as they will know the targets for new drugs.
There are currently 125M shares outstanding with 35-40M restricted shares due to be issued to Research Capital and ADOT.
It is worth registering (costs nothing) and listening to the entire interview.
Genetics of Skin and Hair Color
Annual Review of Genetics
December 2003, Vol. 37, pp. 67-90
First published online as a Review in Advance on June 17, 2003
GENETICS OF HAIR AND SKIN COLOR
Jonathan L. Rees
Systems Group, Dermatology, University of Edinburgh, Lauriston Buildings, Lauriston Place, Edinburgh, EH3 9YW, United Kingdom; email: jrees@staffmail.ed.ac.uk
Abstract
Differences in skin and hair color are principally genetically determined and are due to variation in the amount, type, and packaging of melanin polymers produced by melanocytes secreted into keratinocytes. Pigmentary phenotype is genetically complex and at a physiological level complicated. Genes determining a number of rare Mendelian disorders of pigmentation such as albinism have been identified, but only one gene, the melanocortin 1 receptor (MCR1), has so far been identified to explain variation in the normal population such as that leading to red hair, freckling, and sun-sensitivity. Genotype-phenotype relations of the MC1R are reviewed, as well as methods to improve the phenotypic assessment of human pigmentary status. It is argued that given advances in model systems, increases in technical facility, and the lower cost of genotype assessment, the lack of standardized phenotype assessment is now a major limit on advance.
Genetics of human pigmentation
Author: E. Healy
Filed: 29/05/2003, 02:17:43
Source: Progress in Forensic Genetics 9
Readers' Comments: (0)
International Congress Series
Volume 1239 , January 2003, Page 559
Progress in Forensic Genetics 9. Proceedings from the 19th International ISFG CongressMünster, 28 August–1 September 2001
Physical traits
E. Healy
Dermatopharmacology, Southampton General Hospital, Tremona Road S016 6YP, Southampton, UK
Available online 7 February 2003.
There is widespread variation in human hair, eye and skin colour, and this results from alterations in the amount and ratio of the two types of melanin pigment, brown-black eumelanin and red-yellow phaeomelanin, in these tissues. Furthermore, in addition to differences in constitutive (untanned) skin pigmentation, there is also variation between individuals in facultative pigmentation (the degree of cutaneous tanning following exposure to single or multiple doses of ultraviolet radiation). In the mouse, over 50 genetic loci are known to be involved in the control of pigmentation, and many patterns of altered coat colour have been demonstrated to result from monogenic abnormalities. In man, however, most inter-individual differences in pigmentation are estimated to result from polymorphisms at approximately four or five genetic loci. Pigmentary disorders resulting from pathological alterations in single genes, including oculocutaneous albinism type I (tyrosinase), oculocutaneous albinism type II (p-gene), piebaldism (c-kit), etc., account for only a minority of the overall variation in human pigmentation.
Research during the last decade on the melanocortin 1 receptor (MC1R) gene has provided evidence for variants in this gene being an important determinant in a substantial amount of the phenotypic variation in normal human pigmentation. MC1R variants are associated with red hair and fair skin, and investigations employing cell transfections and transgenic mice have confirmed that certain variants are compromised in their ability to signal intracellularly via cAMP, and to promote the synthesis of eumelanin. The complete absence of non-synonymous variants in African negroes, and their prevalence in white Caucasians suggests that most non-synonymous MC1R variants may result in lighter skin colour. Case control studies support a role for MC1R variants, when present in the heterozygous state, in causing fair skin type, and kindred studies suggest that the majority of red-haired individuals have two variant MC1R alleles. However, over 30 MC1R variants have been identified to date, and further research is necessary to characterise the effects of the majority of the less frequently encountered variants, as well as to identify the other genes which determine variation in normal human pigmentation.
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...
Compositions and methods for detecting polymorphisms associated with pigmentation
United States Patent Application 20030211486
Frudakis, Tony N.
November 13, 2003
[0009] The present invention relates to methods for inferring a genetic pigmentation trait of a human subject from a nucleic acid sample or a polypeptide sample of the subject, and compositions for practicing such methods. The methods of the invention are based, in part, on the identification of single nucleotide polymorphisms (SNPs) that, alone or in combination, allow an inference to be drawn as to a genetic pigmentation trait such as hair shade, hair color, eye shade, or eye color, and further allow an inference to be drawn as to race. As such, the compositions and methods of the invention are useful, for example, as forensic tools for obtaining information relating to physical characteristics of a potential crime victim or a perpetrator of a crime from a nucleic acid sample present at a crime scene, and as tools to assist in breeding domesticated animals, livestock, and the like to contain a pigmentation trait as desired.
[0010] A method of the invention can be performed, for example, by identifying in a nucleic acid sample at least one pigmentation-related haplotype allele of at least one pigmentation gene, wherein the pigmentation gene is oculocutaneous albinism II (OCA2), agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), adaptor-related protein complex 3, beta 1 subunit (AP3B1) (also known as adaptin B 1 protein (ADP1)), adaptin 3 D subunit 1 (AP3D1), dopachrome tautomerase (DCT), silver homolog (SILV), AIM-1 protein (LOC51151), proopiomelanocortin (POMC), ocular albinism 1 (OA 1), microphthalmia-associated transcription factor (MITF), myosin VA (MYO5A), RAB27A, coagulation factor II (thrombin) receptor-like 1 (F2RL1), or Adaptin 3 D subunit 1 (AP3D 1) whereby the haplotype allele is associated with the pigmentation trait, thereby inferring the genetic pigmentation trait of the subject. In one embodiment, the pigmentation gene includes at least one of OCA2, ASIP, TYRP1, TYR, SILV AP3B 1, AP3D1, AP3D1, or DCT, and the pigmentation-related haplotype allele is a penetrant pigmentation-related haplotype allele, which allows an inference to be drawn as to a pigmentation trait of a subject from which the nucleic acid sample was obtained. For example, where the genetic pigmentation trait is eye shade, a pigmentation-related haplotype allele can be identified in at least one of the OCA2, TYRP1, or DCT gene.
[0013] As disclosed herein, the identification of at least one penetrant pigmentation-related haplotype allele of at least one pigmentation gene allows an inference to be drawn as to a genetic pigmentation trait of a human subject. An inference drawn according to a method of the invention can be strengthened by identifying a second, third, fourth or more penetrant pigmentation related haplotype alleles and/or one or more latent pigmentation related haplotype alleles in the same pigmentation gene or in one or more other pigmentation genes. Accordingly, in another embodiment, a method of the invention can further include identifying in the nucleic acid sample at least a second penetrant pigmentation related haplotype allele of the first pigmentation gene and/or at least one penetrant pigmentation-related haplotype allele of at least a second pigmentation gene, for example, of an OCA2, ASIP, TYRP1, TYR, AP3B1, AP3D1, DCT, SILV, LOC51151, AIM1, POMC, OA1, MITF, MYOSA, RAB27A, F2RL1, AP3D1, or melanocortin-1 receptor (MC1R) gene.
The point is that, yet again, there is a vast difference between the relatively high level seen in the current literature and the detail contained in DNAP's patent applications.
Who will Phenomed collaborate with?
Some relevant text from their website:
http://www.phenomed.net/
PhenoMed is a development-stage disease management and medical and pharmaceutical therapeutic company using genomic-based diagnostics to assist health practitioners in their efforts to improve patient outcomes.
Working closely with its U.S. partner, Genomed, Inc., along with research labs in the region, PhenoMed is building a network of physician and health services organizations to quickly expand its medical and therapeutic services offerings throughout the Asia-Pacific region.
http://www.phenomed.net/news1-26-04.htm
Phenomed Sdn Bhd Initiating Clinical Trials Program for SARS and other Infectious Diseases
Physicians and Health Care Groups Encouraged to Participate in Clinical Trials
KUALA LUMPUR, Malaysia – January 26, 2004 – Phenomed Sdn Bhd, a development-stage disease management and medical-pharmaceutical therapeutic company, announces the initiation of its clinical trials program for infectious diseases.
"Phenomed is announcing that it will begin collecting information from government agencies, physicians and individual patients interested in participating in the company's clinical trials program. We are working closely with our US partner, Genomed, Inc., and that company's CEO and Chief Medical Officer, Dr. David Moskowitz in helping to sign up interested parties," said Ezehan Reza Kamaluddin, Phenomed's interim Chief Operating Officer. "There is a worldwide need for disease management and targeted pharmaceutical therapeutics directed at infectious disease. Malaysia's disease management needs are ever-present and Phenomed wants to do all it can to help in meeting the country's healthcare needs in fighting these persistent scourges. The immediate concern over avian flu highlights this need."
...
How do you identify people that will be involved in the clinical trials program? One way is to look at people that have previously been involved in similar work in conjunction with the Phenomed principals. Here I identify one such individual.
Here are a couple of quotes from a press release of January 12, 2002:
http://www.bioenterprise.org/dengue-NUSpressRelease(HTML).htm
AP Genomics to Launch Innovative Dengue Diagnostic Kit Based on Home-Grown NUS Technology
"The need for a more effective and practical approach to diagnosis of dengue is so great - we immediately recognized the immense public health potential of A/Prof Chow's primers, and its use for accelerating diagnosis of the disease." said Dr. Gurinder Shahi, Interim CEO for AP Genomics and CEO of BioEnterprise Asia, the accelerator facilitating technology and business development for AP Genomics."
Dr. Nor Shahidah Khairullah, Head of Virology at the Infectious Diseases Research Centre, Institute for Medical Research in Malaysia, is anticipated to oversee the testing for field validation of the dengue diagnostic technology. "The development of this test represents a major advance in dengue diagnostics, and will also be a boon for studying the molecular epidemiology of the disease - it could have substantial public health significance" she said "We believe it will be only the first of many innovative diagnostic tools we are planning to develop and validate with AP Genomics."
Dr. Nor Shahidah Khairullah, of the IMR in Malaysia, said, "the availability of such a product will greatly facilitate molecular epidemiology and diagnosis of dengue. IMR is planning to work with AP Genomics and is proud to be associated with the development effort for this exciting new product, and we look forward to many years of cooperation and collaboration in product and technology development with AP Genomics."
...
Apart from being the Head of Virology at the IMR, Dr. Nor Shahidah Khairullah is also a member of the Medical Research & Ethics Committee (MREC), Ministry of Health Malaysia:
http://www.imr.gov.my/MREC.htm
Here is a Malaysian Ministry of Health presentation:
http://webjka.dph.gov.my/aids/bss/1workshop/MALAYSIA.ppt
This bit:
http://webjka.dph.gov.my/aids/bss/1workshop/36
is concerned with HIV Diagnosis in Malaysia. The presenter was Dr Nor Shahidah Khairullah MBBS, MSc, FRCPath, FAMM, Head of Virology and Director National AIDS Reference Laboratory.
She regularly takes part in conferences and workshops. Here she is at the Intracom conference in October 2003:
http://www.ninpv.org/5thIntracom/201003.htm
Special Lecture
Integrated Medicine – Addressing the Gap
Dr Nor Shahidah Khairullah
Here she is giving a presentation on clinical trials:
http://www.bpfk.gov.my/tcmconferenceprogramme.htm
Clinical Trial of T/CM Product Towards Compliance to GCP
Dr. Nor Shahidah Khairullah, Consultant Virologist and Head of Virology Unit, Infectious Diseases Research Centre, Institute for Medical Research, Malaysia
The presentation itself contains a nice overview of the clinical trials process in Malaysia:
http://www.bpfk.gov.my/pdfworddownload/21.ppt
Finally, here is an article on her work with SARS:
http://www.orifresh.com/NEWSFLASH.htm
Testing time for researchers
in Malaysia
Scientists in Malaysia are quietly studying the SARS virus and are achieving some positive results. Audrey Edwards speaks to Dr Nor Shahidah Khairullah of the Institute for Medical Research to piece together the puzzle
DR Nor Shahidah Khairullah is probably facing the challenge of her lifetime as she and her staff at the Institute of Medical Research (IMR) work tirelessly to conduct tests on specimens suspected to contain the SARS virus.
“It is a tough but exciting job. And I like challenges,' she says simply.
Ever since the IMR's P3 laboratory was activated in mid-March to work on the SARS outbreak, Dr Nor Shahidah, who also heads the Institute of Medical Research (IMR) virology unit, and her team of 20 comprising scientists, doctors, research officers and technicians have been working non-stop testing the specimens that have been referred to them by various hospitals and institutes throughout the country. This is the first time that the laboratory is being used for a real viral outbreak, reveals Dr Nor Shahidah who is on a two-year contract with IMR, which ends this August.
It is also one of two P3 labs in the country, the other being at the Veterinary Research Institute in Ipoh. (A P3 lab undertakes work on viruses such as HIV and Hepatitis.)
“I’m very proud of my lab. I think we are doing a lot. The staff is on call every day,” she says.
A very hands-on person, Dr Nor Shahidah is also involved in the testing process, performing tests such as studying the immuno fluorescent slides and doing cell culture.
“I verify and look at the tubes myself. Even if you are the head, you have to be hands on,” she says. “You cannot just be an administrator, you must be the driving force.”
A typical day for her begins at 7.15am and ends about 10pm. She spends the day doing a host of things including looking through the number of specimens received the previous day, repeating tests, screening pending cases, attending ministry meetings, teaching and doing administrative work.
“I have a very close relationship with my staff but I will keep tabs on them and what they are doing. They have to be trained to be detailed in their work,” she says.
She is lucky if she gets five hours of sleep daily, she says, but the adrenaline and the passion for work keeps her going.
“Viruses intrigue me. It infects a person and you study the outcome on humans and their immune system. Another passion for me is looking at the potential of herbal medical products on viral diseases.”
The scale of activities at the lab since it was co-opted in the fight to contain the outbreak of SARS in the country has affected the personal life of everyone involved here, she says.
Going to work early in the morning and coming back late at night, you do not get to see daylight at all, she relates. “My three children are complaining that they do not see me anymore.”
So when she has time to spare, she and her family watch movies and play with their menagerie of cats, terrapins, turtles and fish.
“We go to the zoo, movies or just sing together. I have simple needs and I want my children to learn from my commitment so they will do the same later on,” she says.
One of her staff, senior research officer Ravindran Thayan, 38, finds the current project in the P3 lab quite exciting. “You feel that your work is important and there is a huge responsibility because people are depending on you. Initially, I was a bit worried (to work in a P3 lab) but if you don’t do it, then who will?” he states.
“You are happy if you get results because it is frustrating when you don’t produce anything.”
After more than a month, he says, they had become “experts” in changing from their normal working clothes to the Tyvex suits.
“We used to take about 10 minutes but now we can do it in three minutes. And we have taken the necessary precautions,” he says, adding that his wife and family were supportive of his job.
Another research officer, Fauziah Md Kassim, 39, is also finding the job exciting but hectic.
“You are on call and what time you get to leave depends on the number of specimens there are to process,” says Fauziah who also had to learn how to handle some of the equipment being used in the work.
“As I am not used to working in a P3 lab, I initially felt clumsy handling the specimens. The size of the glove (attached to the casing) was too big,” she says.
Like their counterparts in hospitals who are involved in containing the SARS outbreak, the team at the IMR P3 lab also know they are working with a dangerous virus.
“My husband was initially worried that I might get infected, but he didn’t say no to my working in the lab because he knows that I will be okay if I follow all the advice,” says Fauziah. “And anyway, I think this job cannot compare to those medical staff who have direct contact with the patients. They are in a riskier position.”
Medical technician Mohd Shamsuddin Mohd Zain, 26, admits that he was initially frightened when he began to work at the P3 lab. “You do feel a bit tense because you really have to concentrate on what you are doing. Sometimes, you have to bring specimens from the P3 lab to be tested downstairs. And you need to know what to do.
“The safety suit and mask can make you feel suffocated in the beginning, but it is okay once you learn how to breathe properly. My family and friends always remind me to be careful. I’m still scared now but it will be fine as long as I am careful,” he says.
The following is Dr Nor Shahidah’s outline of the various aspects connected with specimen testing and the work of the team at the IMR’s P3 lab.
Transporting specimens
Guidelines on the correct way of transporting specimens have been given to hospitals and institutions that obtain specimens from patients.
Specimens include organs, sputum, throat and nasal swab, and excretions.
“The specimens are transported to us in ice. Before transportation, the specimens are packaged in three layers,” Dr Nor Shahidah explains.
“Swabs are put in a viral transport medium. This is to preserve the specimens and make sure spillages don’t occur to protect the person transporting it.”
However, processing could run into problems when specimens are not labelled properly, contaminated, arrive late, sent without adequate information or when wrong specimens are sent, she says.
“The doctors in charge have to take care when sending specimens because we don’t want to take repeat specimens. And they should send more specimens to us when the patient’s condition worsens,’’ she adds.
The lab setting
The high containment lab is set at negative pressure (where air from outside would flow in when the door is opened and not vice versa).
Strict standard operating procedures also need to be observed by staff working there. These include making sure that the pressure in the lab is correct, maintaining the equipment and cleaning up after they leave. Everyone also has to wear Tyvex suits (full body suits), double gloves, N100 face masks and goggles.
Dr Nor Shahidah says the lab is divided into three sections: reception, changing room, which has an attached airlock, and the lab itself.
Specimens are passed to staff in the high containment lab through a “pass box”. They then start to sort them out.
“They see what specimens have been sent, and look at the form to make sure the labels on the specimen match the one on the form. If the wrong specimen has been sent, then it cannot be processed,” Dr Nor Shahidah says.
Once all this is verified, they write out a work sheet and fax it to the operations room in IMR. Nothing that goes into the P3 lab comes out unless it has been decontaminated and autoclaved, she said.
Her staff in the P3 lab work on a rotation basis and practise a “buddy system”.
“In case something happens, they will always have back-up so no one is allowed to go in alone,” she explains.
The tests
The type of tests done depends on the specimens used.
Five tests: cell culture, electron microscopy, immuno fluorescence antibody technique (IFAT), polymerase chain reaction (PCR) and real time PCR are carried out in three labs at the IMR. The labs are electron microscopy, cell culture (where IFAT is also done) and molecular diagnosis (PCR and real time PCR).
To confirm that a specimen is positive for SARS, at least two kinds of tests are needed, Dr Nor Shahidah says.
“This can be PCR and IFAT. Even then, we repeat the tests twice. We also test all specimens that come to us.”
They achieved a triumph of sorts when they obtained seven positive isolates, which meant they could proceed to do other experiments.
“When there is a positive isolate (cultured virus), we have to go through the whole battery for confirmation as sometimes you get a citopathic effect that is due to different kinds of viruses. So you have to confirm whether it is SARS or not,” she says.
But a negative result also does not mean there is no SARS virus, she cautions.
“Once you have confirmed that you have the SARS virus, then you can grow it. You can do sequencing of the coronavirus (which is the biggest RNA virus) and when you get that, you can compare this isolate with those from other countries and see if ours is the same as theirs.
“You can also get virus antigens, which can be used in diagnostic tests.”
Malaysia is also trying to standardise its own test kit in real time PCR and IFAT, and the IMR is evaluating the Artus kit (a German diagnostic kit).
The misconception
One major misconception among people, including doctors, was that test results would be quick, says Dr Nor Shahidah.
“They must understand that it is a process. The fastest it takes to get a result is three to four days, which is through IFAT, molecular diagnostics or electron microscopy. Cell culture takes two weeks.
“Sometimes it is frustrating to get calls from doctors who ask why there are no results and who say they need the results to determine what to do next. They shouldn’t stop dead in their tracks (of treating patients) while waiting for the results,” she says, pointing out that SARS was diagnosed clinically and that lab testing was done just to confirm the clinical diagnosis.
Patients who come in after two days of illness and have been warded for about three days, says Dr Nor Shahidah, do not produce antibodies yet.
“Don’t expect their antibodies to be at a level where it will test positive for immuno fluorescent. It could be positive later on, though, and this would require a second serum specimen.”
All said and done, Malaysia is doing its fair share of work to stem the spread of the killer virus, whether in public health measures, precautionary measures or testing. The Star
...
Looks like she could be a very useful person to be associated with Phenomed's work given her expertise in areas such as HIV, SARS, clinical trials, etc.; not to mention her role at the Ministry of Health.
DNA can unlock genealogical mysteries
http://www.sunherald.com/mld/sunherald/living/8011985.htm
Posted on Sun, Feb. 22, 2004
DNA can unlock genealogical mysteries
DNA testing, a technique we hear about daily in criminal investigations, has also been affecting genealogical research for the past few years.
Slowly, people who have been puzzled by uncertain lineage are seeing genealogy DNA analysis as a possible breakthrough.
The most common application is Y-chromosome testing for people with the same surname. Y-DNA is passed from father to son through the generations. Therefore, men with the same paternal lineage would share the same genetic patterns. People who undertake this type of a DNA project usually have one of several motives. They might want to prove whether all people of a certain surname have common roots or whether people with the same surname can be grouped into different families.
They might want to determine whether two or more families in various geographical areas share a common ancestor. Or, they may want to solve the questionable paternity of an ancestor.
There are an estimated 800 surname projects ongoing at various laboratories and others are being planned. Among the most recent is a Creel search, initiated by several men who are seeking others who have an unbroken Creel line as far back as early Colonial times. For information, e-mail dtcreel@sbcglobal.net. Another recent project is seeking people of Munro descent. For information, e-mail Margaret Bardin, mbardin@ghg.net, or DeAnn Monroe Steely, dsteely@yahoo.com.
Some people who are curious about their deeper origins want to learn if that legendary Indian princess is really part of their family tree, or their percentage of European, African or Asian blood. Mitochondrial DNA (MtDNA) testing, which traces the maternal line, is often used in such projects.
FamilyTree DNA, one of the leading companies in genealogy DNA testing, said their research in the biogeographical field has found that about a third of all Caucasians have some Southeast Asian ancestry. This is a result of migrations into Europe by nomadic tribes in ancient times.
African Ancestry Inc. of Washington, D.C., is one of the labs that specializes in pinpointing the area of Africa from which a family originates. The company has compiled a DNA database of 10,000 people from 85 ethnic groups in Africa. Each group has certain genetic markers not found in other people.
Trace Genetics of Davis, Calif., offers Native-American testing.
Information on various companies specializing in genealogy DNA may be found on the Internet at genealogy.about.com/cs/dna testing. To learn more about the various DNA surname projects that have been launched, check freepages.genealogy.rootsweb/~allpoms/genetics1a.html or Kevin Duerinck's Surname DNA Projects, www.duerinck.com/surname.html. The cost of genealogy DNA testing varies, depending on the number of markers one decides to check and whether one is part of a group test. However, one can expect to pay an average of $200 a person.
Many interesting articles on this subject are available in various genealogy periodicals, such as "Family Chronicle," and online.
Fascinating results in testing done thus far and a growing curiosity among family historians assure that DNA will play an important role in the future of genealogy. But it can never replace old-fashioned research in original records to link our ancestors through the generations.
Book sale
Ancestry.Com is offering the book "Finding Your African American Ancestry," at the sale price of $9.95 through Feb. 27.
This 188-page book emphasizes the newest technology in genealogy, as well as traditional and unique sources in identifying African-American ancestors.
Included are David Thackery's chapters in "The Source and Guide to African American Research at the Newberry Library," case studies and Internet sources. A bibliography for future study is a valuable part of this work.
To order through the Internet, go to www.ancestry.com and click on "shop," or call (800) ANCESTRY.
African-American workshop
This is the last week to make reservations for Beauvoir's free lecture and workshop on tracking African Americans before Emancipation on Saturday, Feb. 28.
The program, which begins at 10 a.m., will be conducted by Anne S. Anderson of Gulfport in observance of Black History Month. The annual program will be in the reading room of the Presidential Library at Beauvoir on U.S. 90 in Biloxi. For more details and reservations call Beauvoir's Tour and Programs Department at (228) 388-9074.
Six degrees of freedom
Fernandez JR, Heo M, Heymsfield SB, Pierson RN Jr, Pi-Sunyer FX, Wang ZM, Wang J, Hayes M, Allison DB, Gallagher D. Is percentage body fat differentially related to body mass index in Hispanic Americans, African Americans, and European Americans? Am J Clin Nutr. 2003 Jan;77(1):71-5.
She is connected. Why is she interesting?
He Q, Horlick M, Fedun B, Wang J, Pierson RN Jr, Heshka S, Gallagher D. Trunk fat and blood pressure in children through puberty. Circulation. 2002 Mar 5;105(9):1093-8.
Here is a link to the full article:
http://circ.ahajournals.org/cgi/content/full/105/9/1093#R34-104706
Limitations of Our Study
It must be acknowledged that the definition of ethnicity based on self-report is limited because of the genetic admixture of populations in the United States. A more objective estimate of biogeographical ancestry involves the use of genetic markers, characterized by particular alleles, which have differential frequencies among racial or ethnic populations.34
The reference cited is:
Shriver MD, Smith MW, Jin L, et al. Ethnic-affiliation estimation by use of population-specific DNA markers. Am J Hum Genet. 1997; 60: 957–964.
http://cpmcnet.columbia.edu/dept/obesectr/NYORC/gallagher.html
http://crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6665991&p_grant_num=1R01HD042187-01A2&am....
Tenuous? Also on the faculty at the New York Obesity Research Center at St. Luke's is Jeanine Albu:
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.
Here are some of the other staff and affiliates:
http://cpmcnet.columbia.edu/dept/obesectr/NYORC/staff.html
It seems that people at St. Luke's are at least aware of biogeographical ancestry and its uses in research.
Johnson & Johnson submission to FDA
Here is J&J's submission to the FDA regarding their proposed pharmacogenomic data submission guidelines (it is the only one I can see on the FDA site):
http://www.fda.gov/ohrms/dockets/dailys/04/jan04/012204/03D-0497_emc-000001-02.pdf
In a wide-ranging response there is a lot of identification of issues that they would like further clarification on from the FDA, together with questions about the responsibility for certain functions. There is also a clear theme related to "flexibility". This is a typical example:
"Restrictive standards on the data format and validation could discourage certain companies from submitting genomic data and possibly even discourage companies from engaging in PGx activities altogether. The standards may apply more to one platform than another and therefore may force companies to change technologies (at considerable cost) or, at least, put them at a disadvantage to companies using “FDA-approved’ technologies. We feel that it would be preferable to allow for a reasonable degree of flexibility in data format and validation for PGx research activities."
Of course if such an approach is allowed we would lose the benefits of standardization of data format and validation. I think we can rely on the good ol' boys at the FDA to provide a certain degree of "flexibility". Now to be fair to J&J, they do also highlight some important issues:
"We routinely refer to the genes as being the biomarkers, yet, for DNA-based studies; it is the alleles that are the markers. Therefore, clarification would be required on the identity of the SNPs (and combinations thereof) which are considered to be “Known Valid Biomarkers” as well as the homozygous vs. heterozygous states that also have an impact on the outcome. This adds another level of complexity that should be clarified but should not be restricting."
Note that word "restricting". The important point is that it is the alleles (SNPs) that are the real biomarkers (informative markers if you will).
terry, the subject matter concerned would be more appropriate for William Thompson to comment on IMO. He is also listed on the website devoted to the defence of the case. I can understand DNAP being contacted to review the case in the context of the potential use of DNA Witness, but I do not see why the defeence team would want such statements from somebody who has never given evidence in court. Thompson has and would have been a more "credible" source IMO.
Irrespective, as I have said before I would like to see DNA Witness used to exonerate those falsly imprisoned. It does not look as if that is going to be the case here.
Ifida, you and me both! Just as long as Tony's comments are concerned with interpretation of DNA Witness results (a subject in which he is an expert) and not DNA contamination (a subject in which I respectfully suggest he is not).
Midave, I take the point and publicity is usually welcome. However, looking at what Tony was quoted as saying, an alternative interpretation of what has occured suggests itself. It is not really fair to discuss an on-going appeal (especially not knowing all the details), but I would suggest that there are valid uses for DNAP's technology and that there are situations where the technology is not applicable - and which we should probably therefore question our involvement in. That is all I am doing.
ifida, without knowing the details of what transpired, I would suggest that this is not really the sort of involvement we want in this sort of case IMO.
Bradenton Herald snippet
http://www.bradenton.com/mld/bradenton/business/8005499.htm
DNAPrint finds distributor for test
DNAPrint genomics Inc. of Sarasota has teamed up with Lynn Peavey Co. of Kansas City to advance the use of DNA Witness in the law enforcement community. DNA Witness is an advanced presumptive DNA test that determines the biogeographical ancestry of an individual. Lynn Peavey provides forensic innovations for use at crime scenes and in labs, reaching more than 17,000 law enforcement agencies across the country.
DNA Witness relevance to Malaysia?
A couple of times we have seen references to forensics on the DNA Phenomics website and on the University website of the new CSO Dr Aziz. Irrespective of the DNAP/DNA Phenomics issue, people might wonder what possible relevance DNA Witness (especially the Ancestry component) could have in Malaysia. After all, aren't most people there Malaysian?
Malaysia is actually one of the most heterogenous populations anywhere in the world. There are about 22 million people. Most population classifications state that there are three main ethnic groups: Malay, Chinese, and Indian. Malays are roughly 60% of the population, Chinese roughly 30%, and Indians roughly 10%. There are several other minority ethnic groups including: Eurasians, Europeans, Arabs, Indonesians, Filipinos, and Pakistanis. There is also a very diverse group of more than 50 types of indigenous peoples from Sabah and Sarawak including the Kadazan, Dusun, Murut, Iban, Orang Ulu, Melanau, Bidayuh, Penan, Orang Asli, Bajau, Rungus, Lotud, Orang Sungei, Kadayan, and Bisaya.
So it would appear that a product like DNA Witness that was capable of differentiating between (at least) the main ethnic groups in Malaysia would be of some use to the Malaysian Police.
I can see very little in the literature about DNA analysis of different ethnic groups in Malaysia. One example concerned with analysis of 9 STR loci is:
Short Tandem Repeat (STR) Data for the AmpFlSTRâ Profiler Loci of Samples from the Malay Population in Malaysia. Forensic Science Communications April 2002, Volume 4, Number 2. Lim Kong Boon, Primulapathi Jaya, Mohd Izuan Othman, N. Hithaya Jeevan, Kee Sue Sing, and Lee Yoon Hin.
http://www.fbi.gov/hq/lab/fsc/backissu/april2002/lim.htm
However, there has been some work undertaken on SNPs related to e.g. the CYP2D6 and MDR1 genes in Malaysian ethnic groups:
Ismail R, Teh LK, Amir J, Alwi Z, Lopez CG. Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia. J Clin Pharm Ther. 2003 Aug;28(4):279-84.
Ismail R, Teh LK. Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia. Eur J Clin Pharmacol. 2001 Oct;57(8):617-8.
Teh LK, Ismail R, Yusoff R, Hussein A, Isa MN, Rahman AR. Heterogeneity of the CYP2D6 gene among Malays in Malaysia. J Clin Pharm Ther. 2001 Jun;26(3):205-11.
Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS, Lee CG. Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics. 2002 Aug;12(6):437-50.
People like Mark Stoneking at PSU have worked in this area in the past:
http://www.promega.com/geneticidproc/ussymp6proc/melton.htm
I also previously highlighted some relevant research in Malaysia:
BIOVALLEY UKM Genomics Laboratory is the interim laboratory of the National Institute for Genomics and Molecular Biology. One of it's approved projects is "Analysis of the Human Genomic Diversity in the Malaysian Population for Potential Medical and Forensic Application" which is described here:
http://202.185.32.213/genomicslab/content/approve_project.php
Human Genome Diversity: Analysis of the Human Genomic Diversity in the Malaysian Population for Potential Medical and Forensic Application
Malaysia is blessed with a multiracial population that offers diversity at the human genomes, both nuclear and mitochondrial. These diverse genomes have been under investigation since 1993 with the view of establishing the genotype and allele frequencies at a number of highly variable loci, in order to use them to identify individuals in forensic investigations and parentage testing. To extend the expertise and to improve capability and capacity in genome-scale analysis of the diverse human genomes of ethnic and indigenous groups in Malaysia, this project aims to investigate human genomic variations of medical and evolutionary importance using standard and advanced technologies for disease and forensic applications. Data obtained from the study will contribute to the understanding of SNPs involvement in diseases and their application in forensic science.
This is the project in a bit more detail:
http://www.nbbnet.gov.my/research%20project/exe%20summary/DrKoh.htm
Dr Koh Chong Lek is the main researcher:
http://www.um.edu.my/FS/StaffDetail.asp?SCode=200
And of course there is another connection:
http://www.a-imbn.org/organizational_structure.htm
Program Committee includes "Koh Chong-Lek, Prof. & Coordinator of Genetics & Molecular Biology, Institute of Biological Sciences, University of Malaya, Malaysia"
Dr. Gurinder Shahi
Executive Director/Coordinator
mjam, I saw your mail which was interesting. It does beg the question of what this PR was all about:
http://www.dnaprint.com/pr_3_6_03.htm
DNAPrint genomics Partners With GeneLink to Develop 'Next Generation' Genetic-Profile Tests for Personalized Cosmetics
Thursday March 6, 11:12 am ET
SARASOTA, Fla., March 6 /PRNewswire-FirstCall/ -- DNAPrint (OTC Bulletin Board: DNAP - News; the "Company"), the world leader in the measurement of population structure for disease genetics, personalized medicine, recreational genomics and forensics profiling, announced today that it has entered into a collaborative agreement with GeneLink (OTC Bulletin Board: GNLK - News) to develop new genetic assessments for a personalization of cosmetics and personal care product marketing. The agreement also names DNAPrint as GeneLink's genotyping partner. Further details were not disclosed.
The parties intend to develop tests that will be used to assess genetic risks for certain common skin deficiencies. The test results are expected to provide a basis for recommending formulations that have been specifically designed to compensate for these deficiencies. Rather than merely marketing a genetic test, DNAPrint will assist GeneLink and its partners, which include Arch Chemical (http://www.bankdna.com/news_articles/02_11_03.asp ), in focusing on offering a preventative solution for certain common dermatological and skin aging problems. The system would be marketed as part of an individualized precautionary health regimen, and offered for sale by distributors and manufactures to the $100 billion plus cosmetics and personal care industry.
DNAPrint's brings its ultra high throughput genotype capability and ADMIXMAP platform to the partnership while GeneLink brings existing tests and methodologies. The companies intend to screen millions of candidate markers and broaden proprietary product offerings.
About the test
Through the expression of certain genes, skin defends itself from photo- aging and from oxidative stress that is caused by certain common, potentially harmful molecules known as free radicals. Other genetic defense measures catalyze the detoxification of certain harmful environmental pollutants and some actually cause mild irritation that results from exposure to common products used in daily living (such as soaps). Though all humans have built-in genetic defense mechanisms, the skin for some people is more adept at certain defenses than for others, and this variability in defensive capability is rooted in the genes. GeneLink's Dermagenetics(TM) assessment measures these genes for individual customers by reading key gene variant sequences called Single Nucleotide Polymorphisms (SNPs). The SNPs are known from decades of public and privately funded research to be associated with accelerated skin aging, skin wrinkling and other specific oxidative stress deficiencies in the skin.
End of PR
Ultimately whether it is a one-off or recurring use of genotyping services or something else is not that important IMO as this is not one of our stated target markets. I always personally put the Genelink initiative in the same category as CMIH. If we see the money fine, but until then...
The content of this one might be upsetting to some people as it involves murdered babies:
http://www.pressofatlanticcity.com/news/atlantic/022004BABYBODY_F20.html
February 20, 2004
Investigators seek mother of newborn who washed ashore
By JOHN BRAND Staff Writer, (609) 272-7275
VENTNOR - It is a strange dichotomy that some would-be mothers do all that is humanly possible to have a baby, and others throw their babies' lives away.
Although Atlantic County prosecutors have not arrested anyone responsible for the death of a newborn baby girl whose body washed ashore in Ventnor last month, a portion of their investigation has been devoted to finding the baby's mother, who has not come forward.
"The identity of the mother would be important," Atlantic County Prosecutor Jeffrey S. Blitz said. "We have not identified the mother. We're attempting to find out who the mother is."
Prosecutors are investigating other clues in hopes of finding the baby's killer, but have not made any arrests at this point.
"No one has been taken into custody and no one has been charged with this crime," Blitz said.
Stories of babies at the center of a homicide investigation first hit mainstream media in 1996.
At that time, two college freshmen, Amy Grossberg and Brian Peterson, delivered their baby in a motel near the University of Delaware, killed it and left it in a nearby Dumpster.
The following year, mothers in Woodbine and Atlantic City left their newborns in toilets.
Also in 1997, local girl Melissa Drexler, of the Forked River section of Lacey Township, gave birth to a baby at her high school prom, put it in a bag and left it in the trash.
Not much has changed in seven years.
On Jan. 17, a passer-by on a Ventnor beach, near Suffolk Avenue, discovered a dead newborn baby girl.
The baby was strangled with some type of ligature - a chord or wire - Blitz said, then she was stuffed into a yellow, nylon laundry bag before being put into the ocean.
Blitz hopes the results of DNA tests, expected some time next week, will help determine the baby's race and contribute a piece to the puzzle.
"I don't know how conclusive the (DNA) tests will be," Blitz said.
Prosecutors are also trying to determine if the origin of the yellow, nylon bag can be traced to a local source, Blitz said.
Although he would not comment on what obstacles investigators face in determining the identity of the baby's killer, Blitz urged the public to get involved in the investigation.
"Anyone who has any information is urged to call the Prosecutor's Office or Crime Stoppers," he said.
The prosecutor's Major Crimes Unit can be reached at (609) 909-7666. Anonymous calls can be made to Crime Stoppers at (800) 658-TIPS (8477).
To e-mail John Brand at The Press:
JBrand@pressofac.com
Who knows if this one if OT or not:
http://home.businesswire.com/portal/index.jsp?epi-content=GENERIC&newsId=20040220005249&news...
We'll have to wait and see. DNA Phenomics must have been doing something since last July when they announced the formation of the company. They have to source products and services from somewhere...
And apart from that there is not a great deal on him. You can find the individual papers easily enough, e.g.:
Fucharoen S, Fucharoen G, Ata K, Aziz S, Hashim S, Hassan K, Fukumaki Y. Molecular characterization and nonradioactive detection of beta-thalassemia in Malaysia. Acta Haematol. 1990;84(2):82-8.
Research Laboratory for Genetic Information, Kyushu University, Fukuoka, Japan.
The spectrum of beta-thalassemia mutations in Malaysia has been determined in 45 beta-thalassemia chromosomes using dot blot hybridization of the polymerase chain reaction amplified DNA and direct DNA sequencing. Eleven different molecular defects, including those previously detected in Chinese, Asian Indians, and American blacks, and a novel frameshift mutation causing beta zero-thalassemia were detected. Since this novel mutation, a T deletion in codon 15 creates a new restriction site for EcoRII enzyme; the mutation could be detected by EcoRII digestion of the appropriate amplified fragment. The results of the present study provide additional information on the molecular heterogeneity of beta-thalassemia in this population. We also demonstrated the nonradioactive detection method of the beta-thalassemia mutation based upon the digoxigenin-labeled oligonucleotide probes.
What I would like to know particularly is what "...series of events provided us with the unexpected opportunity of being able to offer the CSO position to Dr. Shaharuddin."
Shaharuddin Aziz
This site mentions his PhD thesis:
http://202.186.179.2/medlib/tesis.html
Shaharuddin Aziz. The effect of oestradiol-17B on the synthesis of uterine HnRNA and mRNA. Glasgow: University of Glasgow, 1979. Doctor of Philosophy.
Dr. Shaharuddin Datuk Aziz
http://www.medicine.ukm.my/index.php?ch=9&pg=37&ac=48
Universiti Kebangsaan Malaysia
Faculty of Medicine
Department of Biochemistry
Shaharuddin bin Aziz BSc., MSc., PhD
Academic Position : Associate Professor
Specialty : Human molecular Biology
DNA profiling in crime investigations
Research Interest :
1.PCR techniques in viral and bacterial species profiling.
2.Biotechnology tests to identify embryonic stem cells.
3.PCR of beta globin genes in thalassemias.
Publications :
PUBLICATIONS & CHAPTERS IN BOOKS (1974-2003)
2 Chapters in “Biochemistry for Development” eds, Ataur Rahman Jinnah Postgraduate Medical Centre
1 Chapter in “The Role of Universities in Developing Nations” ed, & publ. Penerbit UKM, Bangi, Selangor, Malaysia
1 Chapter in “Recent Progress in Thyroidology” eds. Endocrine Soc. Thailand Crystal House Press, Bangkok, Thailand
3 Chapters in “Advances in Biochemistry in Asia & Oceania” eds, Biochem Soc. Malaysia Publication. Kuala Lumpur
RESEARCH PAPER PUBLICATIONS IN REFEREED JOURNALS (1974-2003)
30 Research papers published in referred international and national journals.
Acta Haemotologica (Switzerland)
J. Biomedicine & Lab. Sci. (Japan/Taiwan)
ASEAN Journal of Clinical Sciences (Singapore)
Med. J. Malaysia (Kuala Lumpur Malaysia)
Eur. J. Biochem. (Denmark & UK)
Biochem Soc. Trans. (UK)
FEBS Letters (Holland)
J. of Steroid Biochemistry (UK)
Biochimica et Biophysica Acta (Holland)
Nuclei Acids Research (USA,UK)
J. Med, Health Lab. Technology Malaysia (Kuala Lumpur, Malaysia)
Proc. Malaysian Biochem Soc. (Kuala Lumpur, Malaysia)
J. Perubatan UKM ( Kuala Lumpur , Malaysia)
Aziz,S. (2003). A compilation of the background and legal issues related to Stem Cell (totipotent cells) Research. submitted to Mal.J.Biochem. Mol.Biol.
Aziz ,S.&Yu-Tien Liu. (2003). DNA Fingerprints of tuberculosis - strain identification of M.tuberculosis. Paper presented to and by YT Liu at the Chinese Society of Microbiology Conference.Rep.Of China to be published in J.Microbiol Immun.&Infection.
Email Address : cdna@medic.ukm.my
Phone : 603-40405503
pioneertx, you're welcome. I hope it does some good.