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Here is a small article from The Mirror (a UK tabloid) from yesterday. This provides a bit more information, although does not mention the company name. Specifically, it looks as if skin pigmentation information was given to the Police.
http://www.mirror.co.uk/news/allnews/tm_objectid=14187771&method=full&siteid=50143&headl...
ANCESTOR DNA CLUE TO RAPIST Apr 28 2004
Test helps hunt for OAP attacker
By Jeff Edwards, Chief Crime Correspondent
NEW clues to a serial rapist who preys on old women were found by a DNA technique that tracks people's ancestry, police said yesterday.
It showed he is around 35 and black, possibly light skinned and came from the Caribbean.
The DNA technology has never been used before in this country. Now the Metropolitan Police will test 200 of its own black officers to help narrow the search to one island.
The man has struck 84 times in 12 years, including rapes and sex attacks on women aged 68 to 93. One victim of 88 was raped twice and nearly died of a perforated bowel.
He broke in during the early hours, cut off electricity and phone, removed light bulbs and shone a powerful torch in their eyes.
Det Supt Simon Morgan said: "The victims were petrified." He added it was a "miracle" no one had died of fright.
Mr Morgan said the man wore a balaclava and black nylon catsuit - possibly motorbike gear, suggesting he may ride one. He added: "He has to be stopped. It's reckless and dangerous. I've met all 31 victims. Unfortunately three have gone to their graves not knowing who he was and why he picked them."
The attacks are believed to have started in 1992 in Forest Hill, South London. He also struck in Croydon, Forest Hill and Dulwich in South London, Orpington and Sidcup in Kent and Warlingham in Surrey.
The DNA clues were revealed after samples from attack scenes were tested by a US firm.
The technology was developed out of research which helped discover the roots of Adam, the boy whose torso was found in the Thames.
Officers have also done familial or mitochondrial testing - used to track down Craig Harman, jailed last week for manslaughter after throwing a brick through a truck windscreen in Camberley, Surrey.
Now detectives are working through a list of 100 people with similar DNA to the rapist.
Here is another article which also gives a bit more background information about the case:
http://www.newsshopper.co.uk/news/lewgreennews/display.var.484117.0.dna_helps_in_hunt_for_evil_rapis...
DNA helps in hunt for evil rapist who targets OAPs
THE hunt for Britain's worst sex attacker has taken a huge step forward.
DNA techniques have revealed the rapist, who has attacked more than 30 elderly women, is originally from the West Indies.
The monster, who has gerontophilia a sexual perversion towards elderly people has carried out attacks in and around Orpington, Catford, Forest Hill, Sidcup and Croydon.
Victims are attacked in their homes by the masked black man, aged around 35, who often cuts phone lines and electricity supplies before he strikes.
He shines a torch into the eyes of his victims before attacking them. He has also committed 170 robberies and break-ins.
Investigating officer Detective Superintendent Simon Morgan said: "We have travelled all over the world comparing DNA samples without success but we believe scientific advancements will allow us to discover which island in the West Indies the suspect's ancestors are from and even what town."
The same technique was used to find out Adam, the boy whose torso was found in the Thames, was from Nigeria.
Here is a small article from The Mirror (a UK tabloid) from yesterday. This provides a bit more information, although does not mention the company name. Specifically, it looks as if skin pigmentation information was given to the Police.
http://www.mirror.co.uk/news/allnews/tm_objectid=14187771&method=full&siteid=50143&headl...
ANCESTOR DNA CLUE TO RAPIST Apr 28 2004
Test helps hunt for OAP attacker
By Jeff Edwards, Chief Crime Correspondent
NEW clues to a serial rapist who preys on old women were found by a DNA technique that tracks people's ancestry, police said yesterday.
It showed he is around 35 and black, possibly light skinned and came from the Caribbean.
The DNA technology has never been used before in this country. Now the Metropolitan Police will test 200 of its own black officers to help narrow the search to one island.
The man has struck 84 times in 12 years, including rapes and sex attacks on women aged 68 to 93. One victim of 88 was raped twice and nearly died of a perforated bowel.
He broke in during the early hours, cut off electricity and phone, removed light bulbs and shone a powerful torch in their eyes.
Det Supt Simon Morgan said: "The victims were petrified." He added it was a "miracle" no one had died of fright.
Mr Morgan said the man wore a balaclava and black nylon catsuit - possibly motorbike gear, suggesting he may ride one. He added: "He has to be stopped. It's reckless and dangerous. I've met all 31 victims. Unfortunately three have gone to their graves not knowing who he was and why he picked them."
The attacks are believed to have started in 1992 in Forest Hill, South London. He also struck in Croydon, Forest Hill and Dulwich in South London, Orpington and Sidcup in Kent and Warlingham in Surrey.
The DNA clues were revealed after samples from attack scenes were tested by a US firm.
The technology was developed out of research which helped discover the roots of Adam, the boy whose torso was found in the Thames.
Officers have also done familial or mitochondrial testing - used to track down Craig Harman, jailed last week for manslaughter after throwing a brick through a truck windscreen in Camberley, Surrey.
Now detectives are working through a list of 100 people with similar DNA to the rapist.
Here are some other mentions of DNA Witness
Lakehead University Paleo-DNA Lab
http://www.ancientdna.com/
Many projects are currently investigating genomic DNA and its use for species identification, population groups, individual identification, heritable disease identification and other genetic traits.
http://www.mrs.umn.edu/academic/chemistry/researchnew.shtml
DNA Training Program this summer in Thunder Bay. Once again, the Paleo-DNA Laboratory at Lakehead University is offering students the opportunity to participate in our Ancient DNA Internship Program. This year we are delivering the program from April 26th to May 14th, 2004 (deadline to apply, Feb. 1, 2004) and again from August 16th to September 3rd, 2004 (deadline to apply April 30, 2004). During the internship, students work in small groups (one instructor to 4 interns) and are given a project depending upon their interests. This maybe genetic analysis of disease in ancient mummies or forensic profiling of a body or many other such projects. As a student, you will learn different extraction methods to compare and contrast on both your own DNA and other samples. You will generate your own DNA profile, determine your own mitochondrial haplogroup/haplotype, your own STR profile, confirm your own sex genetically and evaluate a great new forensic technique known as DNA Witness or identify your ancestry by DNA. Students will learn about the different types of DNA that can be analyzed: mitochondrial, nuclear, chloroplast and pathogenic DNA. You will be taught different methods of analysis PCR-RFLP, multiplex PCR, sequencing, regular PCR and electrophoresis. You will learn different methods of sample preparation from a number of different tissue types like bone, teeth, hair, blood residues and mummified tissue. You will understand the use of genetic analysis and its potential in archaeozoology, paleopathology, archaeology, forensic science, paleobotany and paleontology. Lectures by professors and senior analysts in the fields of archeology, genetics, ancient DNA, forensic science, paleopathology and more are integrated with the laboratory sessions.
Details of the above internship are also found here:
http://www.physanth.org/newsletter/winter04.pdf
Crime Spider
Crime Spider Crawls the Web for the Best Crime and Law Enforcement Sites
http://www.crimespider.net/cgi-bin/extremesearch.cgi?dir=Criminalistics/DNA
DNAWitness is a tool that can help solve your crime by narrowing your suspect field. For medical examiners and forensics laboratories, DNAWitness can be used to help prioritize large crime scene samples.
DNA goes to school
http://www.eldnavaalaescuela.com/indexing.htm
DNA goes to school is an international nonprofit organization that aims at informing and educating the public about ethical issues and scientific advances in the biomedical field
http://www.eldnavaalaescuela.com/Gene-Papo47.html
DNA Witness
É a nova tecnologia forense desenvolvida por uma empresa americana. A partir de uma amostra de DNA deixada na cena do crime, a empresa DNAPrint Genomics produziu um possível perfil do criminoso a partir da informação contida no DNA. Confira você mesmo e tire suas próprias conclusões. Em inglês.
http://bioforensics.com/conference/Racial%20Identification/Racial%20Profiling.htm
http://bioforensics.com/conference/Racial%20Identification/
http://biz.yahoo.com/prnews/031015/flw020_1.html
Google translation from Portuguese:
It is the new forensic technology developed by an American company. From a sample of DNA left in the scene of the crime, the company DNAPrint Genomics produced a possible profile of the criminal from the information contained in the DNA. Confira you yourselves and takes off its proper conclusions. In English.
As always the "About DNAPrint genomics, Inc." section is itself interesting:
DNAPrint genomics Inc. uses proprietary human genome research methods to develop genomic-based services and products. The Company introduced ANCESTRYbyDNA(TM) in the consumer market and DNAWitness(TM) in the forensic market in 2003. DNAPrint(TM) is developing products in the pharmacogenomic market and has a disease gene discovery program.
The Belarus news is very positive. This is IMO the sort of opportunity that we have been waiting for: a group of doctors who are not constrained in the same way that their counterparts in the US are, who have a pressing unmet need in a relatively large target patient population which the GMED protocol can hopefully address.
Let me ask a question, based on GMED's 10K. How are GMED going to offer genotyping services to Phenomed priced at $0.50 per genotype?
They are a reseller. DNAP and Orchid are basically different animals, although there is some synergy/competition in the forensic area.
W2P, all preparation for Ancestry version 3.0 IMO. I think the company previously said they needed circa 750K to develop this version, which they can now obviously do. It will be very interesting indeed to see who is added to the SAB.
Here are the main points:
As of December 31, 2003, we had 125,691,027 shares outstanding. As of December 31, 2003, we had 48,234,831 options outstanding. As of March 18, 2004, we had 187,716,591 shares outstanding.
This is where the additional shares went to:
On January 8, 2004, we sold 4,703,633 shares of our common stock at $0.0213 per share or an aggregate of $100,000 to Research Capital
On January 9, 2004, we sold 11,121,409 shares of our common stock to Advanced Optics Electronics at $0.027 per share or an aggregate of $300,000.
On January 23, 2004, we issued 1,000,000 shares of our common stock to Peter Brooks in connection with his exercise of options granted to him. The options were exercised at $0.006 per share or an aggregate of $6,000.
On February 5, 2004, we issued 6,679,435 shares of our common stock to Research Capital for debt conversion of $180,657.
On February 5, 2004, we issued 100,000 shares of our common stock to Scott Williams in connection with his exercise of options granted to him. The options were exercised at $0.025 per share or an aggregate of $2,500.
On February 6, 2004, we sold 11,121,411 shares of our common stock to Advanced Optics Electronics at $0.027 per share or an aggregate of $300,000.
On February 9, 2004, we issued 769,231 shares of our common stock to Keith Boyer in connection with his exercise of 769,231 warrants at an exercise price of $0.05 or an aggregate exercise price of $38,461.
On March 8, 2004, in connection with our agreement with Pierpoint Investments, we sold 833,333 shares of our common stock to Robin Carr at $0.045 per share or an aggregate of $37,500.
On March 10, 2004, we sold 11,121,410 shares of our common stock to Advanced Optics Electronics at $0.027 per share or an aggregate of $300,000.
On March 11, 2004, in connection with our agreement with Pierpoint Investments, we sold 411,112 shares of our common stock to N. Shah at $0.045 per share or an aggregate of $18,500.
On March 11, 2004, in connection with our agreement with Pierpoint Investments, we sold 411,112 shares of our common stock to A. Desch at $0.045 per share or an aggregate of $18,500.
On March 11, 2004, in connection with our agreement with Pierpoint Investments, we sold 204,445 shares of our common stock to L. Fitzpatrick at $0.045 per share or an aggregate of $9,200.
On March 12, 2004, we sold 6,012,658 shares of our common stock at $0.0632 per share or an aggregate of $380,000 to Research Capital.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 200,000 shares of our common stock to L. Fitzpatrick at $0.045 per share or an aggregate of $9,000.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 200,000 shares of our common stock to I. Patel at $0.045 per share or an aggregate of $9,000.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 200,000 shares of our common stock to D. Limmer at $0.045 per share or an aggregate of $9,000.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 200,000 shares of our common stock to Weighill Builders at $0.045 per share or an aggregate of $9,000.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 111,112 shares of our common stock to R. Shah at $0.045 per share or an aggregate of $5,000.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 150,000 shares of our common stock to L. Peterman at $0.045 per share or an aggregate of $6,750.
On March 18, 2004, in connection with our agreement with Pierpoint Investments, we sold 150,000 shares of our common stock to M. Paerse at $0.045 per share or an aggregate of $6,750.
On March 18, 2004, we issued 6,058,560 shares of common stock to Research Capital for debt conversion of $153,081.
During 2003 we targeted the discovery of disease genes associated with Type 2 Diabetes and Colon Cancer, but lacked the funding to do so. During 2004, our next phase of operations, we have decided to focus solely on identifying genes for common cancers, since we believe we can already prevent type 2 diabetes itself and its complications. Cancer-causing genes affect a large population base with ample opportunities for disease-gene related products and services. The first samples to be collected will involve such common cancers as lung, prostate, colon, breast and pancreas.
We will accomplish our analysis of individual SNPS, as previously defined under "Our Research and Development Approach", through ultra-high throughput (UHT) machines. Genotyping consists of two phases: screening, wherein a relatively small number of cases and controls are genotyped at a large number of SNPs, and validation, wherein a considerably larger number of cases and controls are genotyped at a small number of SNPs. The Orchid UHT machine we purchased and installed at DNAprint Genomics, for example, will accomplish validation genotyping.
To date we have earned only $6,410 of revenues.
Currently, a patient can subscribe to our Clinical Outcomes Improvement Program(tm) for $67 a month. We have twelve such agreements.
During 2001, we spent $333,264 on our research and development. During 2002 and 2003, we spent no funds on research and development.
We have no part-time employees. We have 1 full-time employee, our President/Chief Executive Officer/Chief Financial Officer/Chief Accounting Officer/Chairman of the Board/Chief Medical Officer, Dr. David Moskowitz, who is responsible for directing our Board of Directors, overseeing all research and development and marketing issues, and supervising all medically-related activities. Additionally, Dr. David Moskowitz is responsible for our overall administration and operation, including finance, marketing, and personnel.
Agreement with Pierpoint Investments SA
On or about March 2, 2004, we entered into a ten year letter of interest with Pierpoint Investments whereby Pierpoint indicated interest in the purchase of $500,000 and $2,000,000 of shares of our common stock per year at the 30 day average of the bid and ask price, less a 25% discount with warrants exercisable at the 30 day average bid and ask price less a 40% discount. During the first year the interests is to purchase $225,000 of common shares at $0.045 per share and an additional $275,000 of shares at the 30 day average bid and ask price less a 25% discount. By investing $225,000 Pierpoint will be eligible to receive 5,000,000 two years warrants exercisable at the 30 day average bid and ask price less a 50% discount. Should the initial $225,000 be received by us, an affiliate of Pierpoint will be eligible to purchase $250,000 of our shares of common stock at $0.045 per share and receive 5,555,556 two year warrants exercisable at 30 day the average bid and ask price less a 50% discount. By investing $500,000 in the first year, Pierpoint will be eligible for a total of 40,000,000 warrants, including the 5,000,000 discussed above. In accordance with the terms of the letter of interest, through April 5, 2004, we issued an aggregate of 3,071,114 shares of our common stock for cash totaling $138,200.
Agreement with E & E Communication
On February 6, 2004, we entered into an agreement with E & E Communications, a public and investor relations company, in which E & E Communications agreed to: (a) assist in the preparation of our news releases and other public announcements; (b) "pitch" our stories to the media, including national, feature and trade press and develop story lines to make us attractive to the major media and financial community; and (c) prepare targeted materials for eh media and potential investors and assist in communications that emphasize the key strengths and competitive advantages of our management, business plan, and technologies. We agree to pay E & E Communications $2,000 a month in exchange for these services. The agreement can be cancelled by E & E Communications or us upon a thirty day notice.
Partnership Agreement with PhenoMed, Sdn Bhd
On September 5, 2003, we entered into an agreement with PhenoMed, Sdn Bhd, doing business as PhenoMed, a Malaysian corporation. This agreement provides that:
o PhenoMed will have the exclusive rights to offer our genomic medical technologies and disease management therapeutics to all customers in the Asia Pacific region, which broadly encompasses that portion of the globe stretching from Western Samoa in the Pacific to Pakistan in the east, and from New Zealand in the south to Mongolia in the north;
o We will license to PhenoMed all necessary technology, know how, and processes required for PhenoMed to implement our disease management program throughout the region, which involves our President/Chief Medical Officer, David Moskowitz to train PhenoMed disease management program-licensed physicians in the proper use of our disease management program;
o We and PhenoMed agree to share equally (50-50) in the net profits obtained from the licensing and sale of the disease management services and related services sold anywhere throughout the Asia - Pacific region;
o Genotyping services provided by us to PhenoMed will be priced at $0.50 per genotype;
o Any of PhenoMed's third party genotyping contracts will abide by the contracted royalty payment and transfer terms we have made with any of our genotyping subcontractors;
o PhenoMed will grant us 15% of the common equity in PhenoMed.
Liquidity and Capital Resources
Cash at December 31, 2003 amounted to $11,469. Cash at April 16, 2004 amounted to $1,498,690.
During March 2004 the Company agreed to adjust the salary of its president to $183,907 per annum with $48,907 being paid in cash and the balance being paid in common shares of the Company with a 50% discount from the average closing price of the 30 day trading period prior to issuance.
During the period from January to April 5, 2004 the Company issued an aggregate of 1,869,231 shares of common stock for cash of $46,962 in addition to the shares described above.
The agreements with ADOT, Pierpoint and E&E are attached to the 10K as appendices.
The 10K is out. Reading it now.
Here's another interesting paper:
Bonilla C, Bertoni B, Gonzalez S, Cardoso H, Brum-Zorrilla N, Sans M. Substantial native American female contribution to the population of Tacuarembo, Uruguay, reveals past episodes of sex-biased gene flow. Am J Human Biol. 2004 May-Jun;16(3):289-97.
National Human Genome Center, Howard University, Washington, DC 20060.
For many years it has been assumed that the population of Uruguay is almost exclusively European-derived and that the biological contribution of the native population as well as of individuals of African descent is negligible. Several recent studies based on a variety of genetic markers, mostly morphological and serological markers, have produced quite a different picture of the constitution of the Uruguayan population. The Native American contribution varies from 1-20%, while the African contribution ranges from 7-15%, in different regions of the country. In the present study we examine the way the admixture process took place in Uruguay by analyzing the ancestry of maternal lineages in a sample from the northern city of Tacuarembo. To accomplish this goal we typed mitochondrial DNA (mtDNA) markers of Native American, African, and European origin and estimated the proportions of each parental group in the admixed population. We found that 62% of all mtDNA haplogroups were of Native American descent, a surprising figure considering the "European roots" of the country. Consequently, this result assimilates Uruguay to the rest of Latin American populations where sex-biased gene flow between European men and Native American women has been the rule. We further analyzed the distribution of the four major founding mitochondrial lineages in Tacuarembo and compared it to other South American populations. We discuss our findings in the light of historical records and assess the need for additional genetic studies. Am. J. Hum. Biol. 16:289-297, 2004. Copyright 2004 Wiley-Liss, Inc.
And who is Carolina Bonilla?
http://anthro.psu.edu/biolab/crew/
Carolina Bonilla, Ph.D. recent graduate in biological anth, Part-Native Guide, cxb471@psu.edu
Here are her publications:
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.
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.
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.
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.
Maybe it's just me, but there seems to be a pattern here...
Incidentally, there was another recent paper on sex-biased admixture:
Wen B, Xie X, Gao S, Li H, Shi H, Song X, Qian T, Xiao C, Jin J, Su B, Lu D, Chakraborty R, Jin L. Analyses of genetic structure of tibeto-burman populations reveals sex-biased admixture in southern tibeto-burmans. Am J Hum Genet. 2004 May;74(5):856-65.
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, Fudan University, Shanghai 200433, China. lijin@fudan.edu.cn
An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2,600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (~62%) and with the southern natives contributing more extensively to the female lineages (~56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications.
DC Rao seems to have been removed from the DNAP website scientific advisors section.
According to the 10K:
"Currently we have two Scientific Advisory Board members and one Board of Consultant member."
"We have initiated plans to expand our scientific advisory board to include other scientists who will actively contribute to our effort in increasing the number of BGA sub-categories from our current four, to as many as 20."
Gin, under no legal pressure per se, but it's one of those things that has to be undertaken by any company that expects to migrate from the pinks (irrespective of how unfair or anachronistic the process is). Personally I wouldn't think that production of the 10K presented any insurmountable issues or that the content would have any material impact (after all they have already indicated this much in the NT 10K filing). Hopefully we will see it soon.
bag8ger, quickly (and hopefully not too flippantly):
1. You would be better off asking the patent examiners.
2. I would think so.
3. Narrow, but it doesn't look like it will apply in practice.
Looks like there is more involved with the Edgarization than might have been previously supposed! Until tomorrow then...
Here's another new paper that is relevant:
Pfaff CL, Barnholtz-Sloan J, Wagner JK, Long JC. Information on ancestry from genetic markers. Genet Epidemiol. 2004 May;26(4):305-15.
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
It is possible to estimate the proportionate contributions of ancestral populations to admixed individuals or populations using genetic markers, but different loci and alleles vary considerably in the amount of information that they provide. Conventionally, the allele frequency difference between parental populations (delta) has been used as the criterion to select informative markers. However, it is unclear how to use delta for multiallelic loci, or populations formed by the mixture of more than two groups. Moreover, several other factors, including the actual ancestral proportions and the relative genetic diversities of the parental populations, affect the information provided by genetic markers. We demonstrate here that using delta as the sole criterion for marker selection is inadequate, and we propose, instead, to use Fisher's information, which is the inverse of the variance of the estimated ancestral contributions. This measure is superior because it is directly related to the precision of ancestry estimates. Although delta is related to Fisher's information, the relationship is neither linear nor simple, and the information can vary widely for markers with identical deltas. Fortunately, Fisher's information is easily computed and formally extends to the situation of multiple alleles and/or parental populations. We examined the distribution of information for SNP and microsatellite loci available in the public domain for a variety of model admixed populations. The information, on average, is higher for microsatellite loci, but exceptional SNPs exceed the best microsatellites. Despite the large number of genetic markers that have been identified for admixture analysis, it appears that information for estimating admixture proportions is limited, and estimates will typically have wide confidence intervals. Copyright 2004 Wiley-Liss,Inc.
The point that on average information is higher for microsatellites, but some SNPs are superior, was also made in this paper in December:
Rosenberg NA, Li LM, Ward R, Pritchard JK. Informativeness of genetic markers for inference of ancestry. Am J Hum Genet. 2003 Dec;73(6):1402-22.
Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA. noahr@usc.edu
Inference of individual ancestry is useful in various applications, such as admixture mapping and structured-association mapping. Using information-theoretic principles, we introduce a general measure, the informativeness for assignment (I(n)), applicable to any number of potential source populations, for determining the amount of information that multiallelic markers provide about individual ancestry. In a worldwide human microsatellite data set, we identify markers of highest informativeness for inference of regional ancestry and for inference of population ancestry within regions; these markers, which are listed in online-only tables in our article, can be useful both in testing for and in controlling the influence of ancestry on case-control genetic association studies. Markers that are informative in one collection of source populations are generally informative in others. Informativeness of random dinucleotides, the most informative class of microsatellites, is five to eight times that of random single-nucleotide polymorphisms (SNPs), but 2%-12% of SNPs have higher informativeness than the median for dinucleotides. Our results can aid in decisions about the type, quantity, and specific choice of markers for use in studies of ancestry.
Carrie Pfaff, the lead author of the paper, should be familiar from this site:
http://www.rps.psu.edu/0201/genetic.html
"...As part of her doctoral research under assistant professor of anthropology Mark Shriver, Pfaff developed a method for documenting the gap between ethnic identity and what she calls "biogeographical ancestry."
And of course Jen Wagner, another of the authors, was also at PSU under Shriver:
http://anthro.psu.edu/biolab/crew/index.html
Good Mates now serving on other ships, left in port, or cast overboard
Esteban J. Parra, Ph.D., Now Assistant Professor in Canada, eparra@utm.utoronto.ca
Carrie Lynn Pfaff, former grad student now postdocing in Michigan with Jeff Long clpfaff@umich.edu
Jen Wagner, former undergrad student now at grad school in Michiganjkwagner@umich.edu
Jill Barnholtz-Sloan (the other author) is interesting as well. She works at the Karmanos Cancer Institute.
Barnholtz-Sloan JS, Sloan AE, Schwartz AG. Racial differences in survival after diagnosis with primary malignant brain tumor. Cancer. 2003 Aug 1;98(3):603-9.
Barnholtz-Sloan JS, de Andrade M, Dyer TD, Chakraborty R. Admixture effects in the traditional linkage analysis of admixed families. Ethn Dis. 2002 Summer;12(3):411-9.
Barnholtz-Sloan JS, Tainsky MA, Abrams J, Severson RK, Qureshi F, Jacques SM, Levin N, Schwartz AG. Ethnic differences in survival among women with ovarian carcinoma. Cancer. 2002 Mar 15;94(6):1886-93.
Barnholtz-Sloan JS, de Andrade M, Chakraborty R. The impact of population admixture on traditional linkage analysis. Ethn Dis. 2001 Autumn;11(3):519-31.
Going back to the paper, a couple of other interesting quotes:
"Moreover, several other factors, including the actual ancestral proportions and the relative genetic diversities of the parental populations, affect the information provided by genetic markers."
"Despite the large number of genetic markers that have been identified for admixture analysis, it appears that information for estimating admixture proportions is limited, and estimates will typically have wide confidence intervals."
It seems that there are some issues with the identification and usage of markers, which of course will be the case for everybody trying to find and use these markers for MALD. The group of people above seem to be at the forefront of the research, and are closely connected to people like Shriver and Chakraborty. This all bodes well IMO. Incidentally, the point about wide confidence levels bears out what DNAP have been saying about AncestryByDNA on RootsWeb.
Doesn't look like it will arrive today, so until tomorrow...
OK, I'll try to have a look at it later this evening (my time) if it is available today.
Here is a Stephen O'Brien presentation about the set of markers for MALD mapping mentioned in the last post:
http://ord.aspensys.com/asp/workshops/Upcoming.asp
Collaborative Approaches to Discovering Genes in African Americans and Hispanics Utilizing Mapping by Admixture Linkage Disequilibrium (MALD)
September 23-24, 2004
NCI Conference Center, Frederick, MD
Contact: Dr. Stephen J. O'Brien, (301) 846-1415
Description: To review development of the new set of markers for MALD mapping in African Americans and to encourage development of such a map for Hispanics, dissemination of knowledge of novel analysis techniques, understanding applicable diseases and designing databases to support MALD analysis.
For those of you who do not follow DNAP, here is a post from the DNAP board about a paper that two of GMED's Scientific Advisors contributed to:
http://www.investorshub.com/boards/read_msg.asp?message_id=2876733
There are some other papers of interest in the May 2004 edition of the American Journal of Human Genetics. Here is one:
A High-Density Admixture Map for Disease Gene Discovery in African Americans
Michael W. Smith,1,2 Nick Patterson,3 James A. Lautenberger,1 Ann L. Truelove,1,2 Gavin J. McDonald,3,4 Alicja Waliszewska,3,5,6 Bailey D. Kessing,1,2 Michael J. Malasky,1,2 Charles Scafe,10 Ernest Le,3 Philip L. De Jager,3,5,6 Andre A. Mignault,4 Zeng Yi,11 Guy de Thé,12 Myron Essex,7 Jean-Louis Sankalé,7 Jason H. Moore,13,14 Kwabena Poku,16 John P. Phair,17 James J. Goedert,18 David Vlahov,19 Scott M. Williams,13,14,15 Sarah A. Tishkoff,20 Cheryl A. Winkler,1,2 Francisco M. De La Vega,10 Trevor Woodage,10 John J. Sninsky,21 David A. Hafler,3,5,6 David Altshuler,3,4,8,9 Dennis A. Gilbert,10 Stephen J. O'Brien,1 and David Reich3,4
1Laboratory of Genomic Diversity, National Cancer Institute, and 2Basic Research Program, Science Applications International Corporation, National Cancer Institute, Frederick, MD; 3Program in Medical and Population Genetics, Broad Institute, Cambridge, MA; 4Department of Genetics and 5Laboratory of Molecular Immunology, Harvard Medical School, 6Center for Neurologic Disease, Brigham and Women's Hospital, 7Harvard AIDS Institute and Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Departments of 8Medicine and 9Molecular Biology, Massachusetts General Hospital, Boston; 10Applied Biosystems, Foster City, CA; 11Institute of Virology, Chinese Academy of Preventive Medicine, Beijing; 12Department of Viral Oncology-Epidemiology, Institut Pasteur, Centre National de la Recherche Scientifique, Paris; 13Department of Molecular Physiology and Biophysics, 14Center for Human Genetics Research, and 15Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN; 16School of Administration, University of Ghana, Legon, Ghana; 17Howard Brown Health Center and Department of Medicine, Northwestern University, Chicago; 18Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; 19Center for Urban Epidemiologic Studies, New York Academy of Medicine, New York; 20Department of Biology, University of Maryland, College Park, MD; and 21Celera Diagnostics, Alameda, CA
Received January 26, 2004; accepted for publication March 3, 2004; electronically published April 14, 2004.
Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing 450,000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3,011 as a MALD map (1.2 cM average spacing). We estimate that this map is 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
Interestingly, two of the authors of this paper (Jason Moore and Scott Williams) are on Genomed's Scientific Advisory Board:
http://www.genomedics.com/index.cfm?action=advisory
Jason Moore, Ph.D.
Dr. Moore received his training in Applied Statistics (M.A.) and Human Genetics (M.S., Ph.D.) at the University of Michigan with a focus on the genetic epidemiology of common, complex diseases such as hypertension and cardiovascular disease. Now an Assistant Professor in the Program in Human Genetics at Vanderbilt University Medical School, Dr. Moore has established himself as a leader in the development and application of cutting-edge statistical and computational methods for identifying genes that influence the risk of common diseases only through complex interactions with other genes and environmental factors. Dr. Moore recently received the 2001 James V. Neel Young Investigator award from the International Genetic Epidemiology Society in connection with his work in this area. His current work includes the development of the Multifactor Dimensionality Reduction (MDR) approach that was used in the first study to demonstrate interactions between more than three single-nucleotide polymorphisms in a common, complex human disease -- sporadic breast cancer. The development of machine learning and pattern recognition approaches such as MDR and the establishment of a 110-processor supercomputer have positioned Dr. Moore to lead efforts to identify combinations of single-nucleotide polymorphisms from among thousands of candidates in order to better predict the risk of common disease such as hypertension, cardiovascular disease, cancer, depression, and diabetes.
Scott Williams, Ph.D.,
Dr. Williams is currently Associate Professor in the Department of Medicine, with appointments in both the Division of Cardiovascular Medicine and the Program in Human Genetics at Vanderbilt University, Nashville, Tennessee.
Dr. Williams is an expert in human genomics who has extensive knowledge of population genetics, genetic epidemiology, molecular genetics, and computing techniques. He has written over 35 articles in the human genomics field which have appeared in various publications, including "Combinations of variations in multiple genes are associated with hypertension," published in the Hypertension Journal during 2000. In 1997, Mr. Williams became Co- Director of Meharry Medical College's Computational Biology Core Facility and began directing a study to find hypertension genes among African American patients, as well as patients from Ghana.
Latest paper from McKeigue, Shriver & Kittles et al:
Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM. Design and analysis of admixture mapping studies. Am J Hum Genet. 2004 May;74(5):965-78.
Noncommunicable Disease Epidemiology Unit, London School of Hygiene & Tropical Medicine, London WC1E 7HT, United Kingdom. clive.hoggart@lshtm.ac.uk
Admixture between populations originating on different continents can be exploited to detect disease susceptibility loci at which risk alleles are distributed differentially between these populations. We first examine the statistical power and mapping resolution of this approach in the limiting situation in which gamete admixture and locus ancestry are measured without uncertainty. We show that, for a rare disease, the most efficient design is to study affected individuals only. In a typical African American population (two-way admixture proportions 0.8/0.2, ancestry crossover rate 2 per 100 cM), a study of 800 affected individuals has 90% power to detect at P values <10(-5) a locus that generates a risk ratio of 2 between populations, with an expected mapping resolution (size of 95% confidence region for the position of the locus) of 4 cM. In practice, to infer locus ancestry from marker data requires Bayesian computationally intensive methods, as implemented in the program ADMIXMAP. Affected-only study designs require strong prior information on the frequencies of each allele given locus ancestry. We show how data from unadmixed and admixed populations can be combined to estimate these ancestry-specific allele frequencies within the admixed population under study, allowing for variation between allele frequencies in unadmixed and admixed populations. Using simulated data based on the genetic structure of the African American population, we show that 60% of information can be extracted in a test for linkage using markers with an ancestry information content of 36% at 3-cM spacing. As in classic linkage studies, the most efficient strategy is to use markers at a moderate density for an initial genome search and then to saturate regions of putative linkage with additional markers, to extract nearly all information about locus ancestry.
And here's the "competition":
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.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) has been proposed as an efficient approach to localizing disease-causing variants that differ in frequency (because of either drift or selection) between two historically separated populations. 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 derived from the ethnic group that carries more disease-susceptibility alleles. The central attraction of admixture mapping is that, since gene flow has occurred recently in modern populations (e.g., in African and Hispanic Americans in the past 20 generations), it is expected that admixture-generated linkage disequilibrium should extend for many centimorgans. High-resolution marker sets are now becoming available to test this approach, but progress will require (a) computational methods to infer ancestral origin at each point in the genome and (b) empirical characterization of the general properties of linkage disequilibrium due to admixture. Here we describe statistical methods to estimate the ancestral origin of a locus on the basis of the composite genotypes of linked markers, and we show that this approach accurately estimates states of ancestral origin along the genome. We apply this approach to show that strong admixture linkage disequilibrium extends, on average, for 17 cM in African Americans. Finally, we present power calculations under varying models of disease risk, sample size, and proportions of ancestry. Studying ~2,500 markers in ~2,500 patients should provide power to detect many regions contributing to common disease. A particularly important result is that the power of an admixture mapping study to detect a locus will be nearly the same for a wide range of mixture scenarios: the mixture proportion should be 10%-90% from both ancestral populations.
Here's a relevant link to the Broad Institute:
http://www.broad.mit.edu/mpg/people.html
Frog, that's interesting because the ruling applies to all records on or before March 1 2004. The "motion for inspection" that has just been added is April and so, theoreticaly, should be available online.
OT: patiencepays, this is a good link as well:
http://www.amtb-dba.org/English/Text/LiaoFan/index.html
Links to the two most recent articles by Frudakis et al:
Sequences Associated With Human Iris Pigmentation. Tony Frudakisa, Matthew Thomasa, Zach Gaskina, K. Venkateswarlua, K. Suresh Chandraa, Siva Ginjupallia, Sitaram Gunturia, Sivamani Natrajana, Viswanathan K. Ponnuswamya, and K. N. Ponnuswamya. Genetics, Vol. 165, 2071-2083, December 2003.
http://www.genetics.org/cgi/content/full/165/4/2071
Tony Frudakis, Venkateswarlu K, Matthew J. Thomas, Zach Gaskin, Siva Ginjupalli, Sitarama Gunturi, Viswanathan Ponnuswamy, Sivamiani Natarajan, and Ponnuswamy Kolathupalayam Nachimuthu. A Classifier for the SNP-Based Inference of Ancestry. J Forensic Sci, July 2003, Vol. 48, No. 4.
http://aafs.micronexx.com/PDF/JOFS/JFS2002079_484/JFS2002079_484.pdf
The Okaloosa County Sheriff's Department have heard of us:
http://www.sheriff-okaloosa.org/Press%20Releases%202004/cc042004.htm
The Cop Column
April, 2004
Sgt. Rick Hord
Public Information Officer
Technology Helping Crime Fighters
In the first year of the 20th Century, police in Britain used brand-new technology when fingerprints on a billiard ball identified and convicted the thief.
The crime may seem quaint to us, but in 1901, decent billiard balls could only be made of ivory, and ivory was scarce. Trafficking in all manner of stolen ivory was a lucrative criminal enterprise.
We seldom see genuine ivory billiard balls any more, but fingerprints are still putting criminals in jail.
What has technology done for us lately? Here are but a few examples:
*Recreating the Crime: One of the most exciting new fields in science is "Forensic Entomology," or the study of what the maggots and other creepy little bugs on and near dead bodies can tell us about the demise of their host. A cutting-edge branch of another field, "Forensic Botany" got its start a few years ago by proving a dead woman's last meal came from Wendy's and not McDonald's. That got her boyfriend off the hook and led investigators to her other lunch date. The same scientists proved a grieving young mother was a murderer by examination of one-cell algae in the water swallowed by her drowned 15-month old son. That proved the little boy did not die in the creek where his body was found, which shot holes in the mother's abduction story.
*Identifying the Culprit. This much is old news: DNA at a crime scene can convict the guilty and exonerate the innocent if you've got a suspect with whom to make a comparison. The next step will be DNA telling us what an unknown suspect looks like. In Louisiana last year, police thought they were looking for a white male suspect, but a private lab said the suspect's DNA came from a black male. The witnesses were wrong, the lab was right. DNA scientist Tony Frudakis predicts, "A few years from now, we're going to have figured out so many traits that a criminal might as well leave his driver's license at the scene..."
*Getting the Bad Jail into Custody. You don't have to be very old to remember when many cops carried "slap-jacks" in their back pockets. Despite what you may see in the movies, we prefer to make arrests without using force. When the suspect won't allow that, we no longer slap him with a chunk of lead sewn into a leather strap. Pepper spray, electric Tasers, and bean-bag shotgun rounds are three items now available for use by the Okaloosa County Sheriff's Office. There will be more in the years ahead. There's a market for ways to bring the reluctant and violent into custody without injury, and good old American Ingenuity is producing an endless stream of products.
Finally, a warning: technology will never replace humans. Don't become complacent in the foolish belief scientists can catch all the crooks. The most effective weapon against crime will always be citizens who aren't afraid to "become involved."
bag9ger, made the same mistake and mine was a cut and paste!
Replied before reading this. You are right of course.
midas, it does get a bit confusing with so many press releases to remember!
"The first patient in the US in 2004."
"The results of Dr. Moskowitz’s first eight patients will be published soon in a peer-reviewed medical journal."
These were treated last year. Here's the original press release:
89% of Patients with West Nile Virus Encephalitis Responded Rapidly to GenoMed's Treatment; Outlook For SARS Equally Good
ST. LOUIS--(September 30, 2003)--GenoMed Inc. ("the Company" or "GenoMed") (National Quotation Bureau’s Pink Sheets Symbol GMED) reported today on its series of 9 consecutive patients with West Nile virus encephalitis. Eight of nine consecutive patients (89%) had disappearance of symptoms within an average of 24 hours of taking an angiotensin II receptor blocker (ARB), a few as early as 12 hours. Three patients, all of whom responded promptly to GenoMed's treatment, were in the highest risk group for dying, i.e. over the age of 70.
Earlier, the Company reported on 10 patients, but one of the patients, a non-responder, turned out not to have West Nile virus antibodies.
Because of the similarity in the body's response to the West Nile virus and the SARS virus, the same treatment should be equally effective against both diseases.
Dr. David Moskowitz, GenoMed's CEO and Chief Medical Officer, said, "Thanks to my wonderful collaborators in Omaha, Nebraska and Pueblo, Colorado, we've gotten a good picture of what angiotensin II blockade can and can't do against West Nile virus. It can't prevent encephalitis, but it can make it disappear faster. So far we haven't seen any recovery if our treatment is delayed until after a patient is already paralyzed. But symptoms of active infection like headache, confusion, delirium, weakness and fatigue have gone away promptly after starting treatment. The lesson is clear: use ARBs or ACE inhibitors early in the course of the disease."
Dr. Moskowitz continued, "Ten percent of people with West Nile virus encephalitis die; among the elderly, the death rate approaches 50%. In view of these alarming statistics, angiotensin II blockade appears to be a very effective treatment indeed. Our treatment is also available immediately to anyone who wants it, assuming our Internet server is up to the task. Every pharmacy in the world carries ACE inhibitors and angiotensin II receptor blockers. I know of no other treatment for West Nile virus encephalitis that is as safe, effective, and universally available as ours."
Dr. Moskowitz ended by saying, "The same, I hope, will hold just as true for SARS. We'll soon find out. I know we can effectively enroll the entire world in our SARS trial, given the power of the Internet."
The West Nile virus epidemic has already peaked in some states, like Colorado, but may continue into November in other regions. By accelerating recovery from infection, GenoMed believes that its treatment will save additional lives during the course of this year's epidemic.
The recurrence of SARS may have already begun, with a few cases recently reported in Singapore. This year's epidemic is expected to start again in Southeast Asia, where it began a year ago.
According to the last 10Q:
http://12.40.163.150/Archives/edgar/data/1169417/000118206303000278/gm10qsb.htm
There were 1 billion shares authorized and 123,235,065 shares issued and outstanding. In March ADOT purchased just over 33 million shares of restricted common stock for $900,000 (this representing some 21% of the common stock).
From the 10Q you can see in Part II (Other Information), Item 2 (Changes in Securities and Use of Proceeds) the limited issuance of shares that has occured in relation to services provided by consultants, and the existing funding agreement with Research Capital.
There is no history of excessive dilution and no indication that there will be such dilution in the foreseeable future.
ifida, great link. A couple of things that Bill Dalton said that stuck me in particular: genomics is seen as "the major contributor" and Moffitt are keen to analyze "populations" at risk. Right at the end they talked about their Telemedicine Advisory Board, which Ron Weinstein is on (he is President of the American Telemedicine Association). I wonder who else is on this august body? Moffitt's Total Cancer Care initiative is certainly innovative. It was interesting that they highlighted relevant structural roadblocks involving the NIH, and used this to contrast how far ahead of the curve Moffitt is. Personally I can't wait to see the outcome of some of the demonstration projects.
Gurinder Shahi quotes in this article:
http://www.whittierdailynews.com/Stories/0,1413,207~12041~2074272,00.html
Article Published: Friday, April 09, 2004 - 4:55:23 PM PST
Biotech potential in Asia debated
By Andrew Blazier, Staff Writer
PASADENA -- While an Asian biotech expert on Friday lauded the sector's growth potential in South and East Asia, a San Marino investor warned return on that investment is far from a sure thing.
With a population of more than 4 billion, Asia is poised for an explosion of innovative biotechnology and pharmaceutical companies in the next few years, Dr. Gurinder Shahi, the founder of a Singapore-based biotech consulting firm, told about 20 bioscience executives and educators at Caltech during the USC Asia Business Forum.
According to Shahi, chief executive of nonprofit BioEnterprise Asia, the focus on India and China as growing centers for outsourced service and manufacturing jobs has ignored what he described as an Asian climate ripe with ideas. Billions of Asians, he said, are hungry for an infusion of American investment capital to create a future wave of high- risk, high-return, high-tech discoveries.
"It's the fastest-growing market in the world right now,' said Shahi, a physician with training in molecular biochemistry and international health policy and management. "There are competencies here we don't have in Asia. Doing something together could be very beneficial for both countries.'
The number of Asian biotech companies skyrocketed to 3,200 this year from 1,200 in 2001 - a 167-percent increase, according to research by BioEnterprise Asia. China led the growth by creating 900 new firms from a base of 100 just three years ago.
The number of biotech companies remained constant in the U.S. and Europe during the same period, at 1,500 and 1,800 firms, respectively.
"There's a tremendous amount of low-hanging fruit in Asia,' Shahi said. He called on the American investors to support biotech growth in Asia with what he called potential high-return investments.
But the pursuit of that fruit, no matter how tempting, is not for the timid. Bruce Blomstrom, a private San Marino venture capitalist who worked for several years in Asia with Abbott Laboratories, said the region is fraught with potential barriers.
Two primary concerns among Western investors are China's often loose application of international intellectual property laws and a currency-exchange policy that can make it difficult for firms to extract the profits they make in Asia.
"We all know Asia is a big opportunity, but how do you get into it?' he asked. "I think it's naive to think you can just manage everything from here. You can't do business abroad unless you're based there.'
A lot has been said about the BioValley initiative in Malaysia, and the potential benefits that this has in relation to Phenomed. Here is an article from yesterday's New Straits Times which highlights some of the problems that have occured with the BioVelley initiative. Not unexpected developments for those familiar with Malaysia, and not something to worry about as such, but it will give you an idea of what is really involved with these sorts of projects.
http://www.emedia.com.my/Current_News/NST/Sunday/Features/20040411084255/Article/indexb_html
COVER STORY: Nurturing hopes for BioValley
Theresa Manvalan
Apr 11:
Business and science are talking, but they’re not holding hands yet to make a go of the BioValley Malaysia initiative.
THERESA MANAVALAN finds a long gestation period, as is the norm with biotechnology.
EXPECT a flurry of bio activity in the next three months. The BioSafety Bill is to be tabled in Parliament in May, the Ministry of Science, Technology and Environment has been restructured and has a new minister, plus the status of the proposed BioValley Malaysia site has been sorted out.
These three things will hopefully send out the right signals to investors to bring their bucks to BioValley, Malaysia's proposed biotechnology hub.
Already, top officials at the reconstituted Ministry of Science, Technology and Innovation are discussing earthworks for the 800-hectare site, on the fringe of the Multi-media Super Corridor near Dengkil, Selangor. This is the location of the Entertainment Village which never took off.
Still, it will be 2006 by the time the three world-class institutes for genomics and molecular biology, agrobiotech and pharmaceutical-nutraceuticals take shape.
Despite fairly good timing — BioValley Malaysia came in the wake of global excitement over the decoding of the human genome — it hasn't pulled its act together enough to earn serious investor confidence.
So far, three companies have signed up to put their plants there.
What biotech companies and hopefuls would like to see are masterplans of the whole site, the insides of the three institutes and infrastructure that would support the biotech industry. Clear timelines would help, too. The three institutes are going to cost RM100 million.
Since the first announcement in 2002 and a fanciful launch early last year, all's been quiet. So silent that the sniggering has started.
It doesn't help that a few biotech start-ups have turned turtle and some relationships with venture capitalists have gone completely sour. But such horror stories are universal.
Overseas, BioValley's blip on the radar screen is as good as gone. Detractors have been openly talking about "personal agendas" which have stalled the project and kept it shrouded in "secrecy".
For those serious about placing their commitment in BioValley — and there are biotech companies which are genuinely interested — it has been a frustrating wait. Some have already moved on.
But this long season of silence was not without some good.
The Eighth Malaysia Plan midterm review announced last October a RM75 million R&D fund under the National Biotechnology Directorate, the Science, Technology and Inno-vation Ministry agency which spearheaded the creation of BioValley. The fund is mainly for biotech research in plants, animals, food, molecular, biopharmacy and natural products.
Along the west coast of the peninsula, State Governments have been looking at biotech as well. With Federal encouragement, satellite hubs are already sprouting in Penang, Negri Sembilan, Malacca, Johor and in Selangor, projects not directly related to BioValley itself. The Sabah and Sarawak Governments are also pushing biotech.
Many feature indigenous knowledge, local raw materials and capitalise on local environments.
The other good thing that has transpired since 2002 is the debate. Malaysians, especially scientists and investors, have had a chance to talk about biotechnology, its issues, its potential and how to get a slice of the pie. They've flirted with local and foreign investors, met venture capitalists and heard the many horror stories of biotechnology.
The first criticism levelled at the whole BioValley project is the apparent over-emphasis on property development. The focus has been on developing the Dengkil site instead of working on legal, funding and talent issues.
"That's not entirely true," says a ministry source. "Developing the site is the Government's contribution to the biotech industry. It's a signal to investors of official commitment. The other issues are being looked at as well." The proposed site is owned by Kumpulan Darul Ehsan Bhd (KDEB), the Selangor Government's investment arm. Its subsidiary, Kumpulan Hartanah Selangor Bhd (KHSB), is the developer of BioValley.
It is understood that KHSB is planning to build residential and commercial properties in the vicinity. Hence, all the talk about property development.
One point of contention is plain old bureaucracy. "Right now, BioValley is sangkut in bureaucracy," says a local biotech executive.
"It's parked at the Ministry of Science, Technology and Innovation where it's never going to move on track. It should be at the Prime Minister's Department where it will get kick-butt motivation everyday just like the MSC. "Anyway, it should be managed by a CEO in pure business style, not government style." Many expect BioValley to play the role of consolidator.
"Biotech R&D has been going on for a long time here," says Kelvin Keh, head of the Malaysian Biotechnology Information Centre, an NGO which promotes understanding of biotech.
"BioValley could be the one that brings it all together and jump-starts the commerce. Certainly, would-be entrepreneurs would appreciate that." The absence of a single agency to promote BioValley is a sore point. Within the ministry, there are at least two departments to see, after which an investor will have to go to Mida. Not encouraging.
"Malaysia has almost everything except a one-stop-shop for biotech which can move permits, approvals and give good advice. Speed and convenience are important," says Paul Edwards, head of GMX Biotech which will build a human insulin plant in Penang. When up and running in 2006, it will produce 300kg annually of insulin.
Edwards cites Ireland and North Carolina as examples of biotech hubs whose success can be attributed to proactive one-stop agencies.
Halim Hamat, secretary-general of the Malaysian Biotehnology Ind-ustry Organisation (MBIO), says BioValley has to be international in every way.
"We need to create a vibrant scientific community to get acceptance worldwide," says Halim. "Its most attractive feature should be the inflow of quality professionals, including Malaysians now working abroad." MBIO, set up a year ago to represent the biotech industry, has about 25 corporate members in life sciences. Members include biopharmaceuticals, food manufacturers, Sirim, Malaysian Palm Oil Board and related professionals like legal firms and event managers.
The absence of a sizeable scientific community is a big issue. Companies have always had trouble recruiting experienced scientists locally. Often, advertisements are answered by Indian and Chinese nationals.
Singapore, which also doesn't have enough experienced scientists, creates a plan to hire scientists from abroad for each serious investor.
"Besides that, what we're really lacking is the commercialisation scientist," says Halim. "The one who takes the science to market." Which raises two major hurdles for BioValley: legal and money.
Licensing, patents and rights are all tied up with funding and investment. "This is where I'd put my energy," says Kim S. Tan, a Malaysianborn entrepreneur who listed three biotech companies on the London Stock Exchange.
"Legal issues easily turn into big problems. They've got to be addressed. There's got to be people to deal with it. Even the smallest biotech project must examine legal issues, have an IP strategy before starting work. Plus, you do need to understand how the investor or VC works or you risk losing everything." Here's one story: Phytes Biotek Sdn Bhd, which intended to manufacture, package and market tongkat ali products, signed a RM20 million deal with Malaysia Venture Capital (Mavcap) which took 30 per cent ownership.
The founders of the company — scientists from academia — have since lost control of the company. Mavcap exercised its rights to take up 75 per cent of stock when timelines went awry and deadlines were not met.
Now, Phytes Biotek wants to buy out Mavcap. But where does a startup which just burned RM20 million get another RM20 million to do that? Malaysian biotech start-ups and their scientific founders are sweating their way to get investors to understand them. Banks rarely touch biotech here mainly because they don't know the subject at all. Venture capitalists are always tough with money, usually asking for more shareholding than any innovator would dream of giving away.
All investors fear a dotcom-like crash, especially when strong evidence that ideas will pan out is hard to formulate. One option is to license early-stage discoveries to deep pocketed compe-titors.
"Licensing is a possibility," says Kim. "Also, biotechs are merging with other biotechs."
OT: Terry, I sent you a mail yesterday but it experienced a delivery failure. Is the email address you listed on RB still current?
Dublin Molecular Medicine Centre
http://www.dmmc.ie/
DUBLIN MOLECULAR MEDICINE CENTRE (DMMC) represents a highly focused research partnership in the life sciences between the University College Dublin (UCD), Trinity College Dublin (TCD) and The Royal College of Surgeons in Ireland (RCSI). A network of affiliated hospitals provides the setting for accelerated translational bioscience.
http://www.dmmc.ie/programmes.htm
The Programme for Human Genomics (PHG)
The landmark completion of the Human Genome Project provides a unique resource for biomedical sciences. The Programme for Human Genomics is a partnership between the Dublin Molecular Medicine Centre (DMMC) comprising UCD & TCD and RCSI's Biopharmaceutical Sciences Network (BSN). This Programme will ultimately create a single Centre of Excellence in Molecular Medicine and Pharmacogenomics. It's over-riding goal is the application of human genomics and proteomics to the study of the pathogenesis, diagnosis and treatment of human disease with a view to identifying new diagnostic markers and therapeutic targets.
The programme has three operational elements:
1. Candidate gene identification through cutting-edge transcriptomic and proteomic research programmes
2. The identification of disease-susceptibility genes by high throughput variant detection, genotyping and gene validation in human disease.
3. The identification of therapeutic targets through state-of-the-art functional genomics, transgenics and gene knockout technologies.
http://www.dmmc.ie/public/itemdetail.cfm?ItemId=93
Call for Biocollection Proposals on the 17-Mar-2004 to 17-Jun-04
The DMMC is committed to the establishment of a number of biological collections that will allow its investigators to test specific research hypotheses. The group charged with deciding which collections are to be given priority have produced a guidance document. Investigators are invited to review this document and revert with proposals for biocollections.
One of the DMMC’s primary objectives is the creation of biological collections that will allow investigators test specific research hypotheses. The DMMC Gene Bank Management Group is charged with deciding which diseases should be included in the initial round of collections under the Programme for Human Genomics. Investigators are invited to consider the guidance contained in the attached consultation document and revert with proposals for collections. Submitting a proposal does not of course mean that you will have to organize the collection itself. If you wish to submit a proposal, please fill out the attached pro-forma and return it to paul.mckeigue@ucd.ie.
In this section there is an attached Guidance & Proforma for Proposals which lists diseases that have been initially suggested.
http://www.dmmc.ie/documents/ACF3620%2Edoc
The DMMC Gene Bank Management Group has been charged by the Strategic Management Group with deciding what diseases shoud be included in the initial round of collections for which support has been awarded by HEA under the Programme for Human Genomics.
The target is to collect at least 3000 cases of each disease that is selected for study. This necessarily limits us to diseases that are common enough to generate enough cases in all-Ireland, unless an international collaboration has been established for the disease under study that provides access to a larger catchment population. The selection of what diseases to study will be based upon the criteria listed in the table on the next page. We expect to be able to collect no more than four diseases: one in each of the areas on which the Programme for Human Genomics focuses (neurosciences, vascular biology, inflammation and immunity, cancer)
What has this got to do with the London School of Hygiene & Tropical Medicine? Nothing:
http://www.ucd.ie/govauth/report16.htm
University College Dublin Report from the Governing Authority from its meeting on 18 February 2003
On the recommendations of the assessment board the Authority appointed Dr Stephen Pennington to the Professorship of Proteomics; Dr Desmond Higgins to the Professorship of Bioinformatics; Dr Paul McKeigue to the Professorship of Genetic Epidemiology and Professor Mark Shucksmith to the Professorship of Agricultural Economics and Rural Policy, all subject to ratification by the Academic Council at its next meeting.
Which is why the contact details listed here look a bit odd:
http://www.eudragene.org/
Coordinator: Paul McKeigue <paul.mckeigue@ucd.ie> Professor of Metabolic and Genetic Epidemiology, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, UK
And of course the first two participating centers listed on this site are the London School of Hygiene & Tropical Medicine and University College Dublin.
W2P, one thing that is quite noticeable is that the number of different people working on ancestry (or ancestral) informative markers has increased dramatically in the past year. Searches of e.g. Google or PubMed increasingly turn up a large number of relevant items.
With regard to the Native Americans, Mike Hammer recently put a big piece of the diaspora puzzle into place:
Zegura SL, Karafet TM, Zhivotovsky LA, Hammer MF. High-resolution SNPs and microsatellite haplotypes point to a single, recent entry of Native American Y chromosomes into the Americas. Mol Biol Evol. 2004 Jan;21(1):164-75.
Department of Anthropology, University of Arizona, USA.
A total of 63 binary polymorphisms and 10 short tandem repeats (STRs) were genotyped on a sample of 2,344 Y chromosomes from 18 Native American, 28 Asian, and 5 European populations to investigate the origin(s) of Native American paternal lineages. All three of Greenberg's major linguistic divisions (including 342 Amerind speakers, 186 Na-Dene speakers, and 60 Aleut-Eskimo speakers) were represented in our sample of 588 Native Americans. Single-nucleotide polymorphism (SNP) analysis indicated that three major haplogroups, denoted as C, Q, and R, accounted for nearly 96% of Native American Y chromosomes. Haplogroups C and Q were deemed to represent early Native American founding Y chromosome lineages; however, most haplogroup R lineages present in Native Americans most likely came from recent admixture with Europeans. Although different phylogeographic and STR diversity patterns for the two major founding haplogroups previously led to the inference that they were carried from Asia to the Americas separately, the hypothesis of a single migration of a polymorphic founding population better fits our expanded database. Phylogenetic analyses of STR variation within haplogroups C and Q traced both lineages to a probable ancestral homeland in the vicinity of the Altai Mountains in Southwest Siberia. Divergence dates between the Altai plus North Asians versus the Native American population system ranged from 10,100 to 17,200 years for all lineages, precluding a very early entry into the Americas.
A UCSF presentation that quotes this study
http://psg-mac43.ucsf.edu/ticr/syllabus/courses/23/2004/03/30/Lecture/notes/Ethnicity%20and%20health...
HGM2004 Human Genome Meeting
Berlin, Germany
4th - 7th April 2004
http://hgm2004.hgu.mrc.ac.uk/Abstracts/Publish/WorkshopPosters/WorkshopPosters04/hgm075.html
HGM2004 Poster Abstracts
4. Complex Disorders
Poster 75
Population Stratification Confounds Asthma Studies Among Latino Americans
1S. Choudhry, 1N.E. Coyle, 1D. Lind, 2H. Tang, 1K. Salari, 1S.L. Clark, 1N. Ung, 1H. Matallana, 1P.C. Avila, 3J. Casal, 3A. Torres, 3S. Nazario, 1M. Toscano, 1R. Castro, 3W. Rodriguez-Cintron, 1Pui-Yan Kwok, 1D. Sheppard, 4M.D. Shriver, 5,6N. Risch, 1E. Ziv, 1E.G. Burchard
1University of California, San Francisco, San Francisco, CA, USA, 2Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3University of Puerto Rico, San Juan, PR, 4Pennsylvania State University, College Station, PA, USA, 5Stanford University, Stanford, CA, USA, 6Kaiser Department of Research, Oakland, CA, USA
Purpose: Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases such as asthma. However, such studies may be confounded in racially admixed populations, such as Latinos. We tested whether population stratification may affect the results of asthma case-control studies in Puerto Ricans and Mexican Americans.
Methods: Mexican American asthmatic probands and ethnically matched controls (360) recruited from the San Francisco Bay Area and Puerto Rican asthmatic probands and matched controls (360) recruited from Puerto Rico were typed for 52 ancestry informative markers (AIMs). These AIMs were selected for their high allele frequency differences between West Africans, Europeans and Native Americans. For each population we tested whether the degree of association between pairs of markers on different chromosomes was greater than expected using a permutation test. Population stratification was assessed by comparing the global differences in allele frequencies between cases and controls.
Results: Among Puerto Ricans, the association between markers on different chromosomes was significantly greater than expected (p<0.0001). Among Mexicans, there was a non-significant trend towards association between markers on different chromosomes (p=0.07). Among Puerto Ricans, 9 of 52 markers were significantly associated with asthma, and there was a significant difference between cases and controls (p=0.00031). Among Mexican Americans, 3 of 52 markers were associated with asthma and there was no significant difference between cases and controls (p=0.44).
Conclusion: Case-control genetic association studies of asthma are susceptible to genetic confounding in Latino populations. Empirical assessment of the effects of stratification will be important to appropriately interpret the results of case-control studies.
This is probably just a coincidence:
http://www.gre.ac.uk/schools/cls/cgi-bin/library/framer.cgi?msrg
"Prof Ian Bruce was a co-founder of Hybaid Ltd, now a part of Life Sciences International..."
http://cgi.uc.edu/~jakey/CV.html
High-throughput Single Nucleotide Polymorphism genotyping by melting curve analysis. Co-inventor: Mark D. Shriver. US and UK Provisional patents filed. Technology licensed to ThermoHybaid, Franklin MA.
Aberdeen News Q&A
http://www.aberdeennews.com/mld/aberdeennews/news/8347032.htm
Posted on Sat, Apr. 03, 2004
No human vaccine exists for West Nile virus
Editor's note: Readers with questions of the what's-going-on-in-northeastern-South-Dakota variety called the American News Line recently. Those questions - which may have been edited - and the answers appear below.
Q. Is there a human vaccine for West Nile virus?
A. No human vaccine exists yet for the virus, but companies are working toward that goal.
In the meantime, a more immediate focus is finding an effective cure for the effects of the virus.
The St. Louis-based GenoMed Inc. has developed a treatment that uses drugs currently in use by primary care physicians everywhere, available in every drugstore and already proven to be safe.
Dr. David Moskowitz theorizes that encephalitis and death result from an over-response by a person's immune system to the West Nile virus. GenoMed's protocol, which is patent-pending, gently suppresses the immune system, thus potentially saving the patient.
The treatment has shown a 90 percent cure rate in trials so far.
For more information, contact Moskowitz at (314) 977-0115 or e-mail him at dwmos kowitz@genomedics.com.