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Another Shriver paper:
Nutr Rev. 2004 Jul;62(7 Pt 2):S69-74.
Using genetic admixture to study the biology of obesity traits and to map genes in admixed populations.
Fernandez JR, Shiver MD.
Division of Physiology and Metabolism, Department and Nutrition Sciences, University of Alabama at Birmingham, 1530 3rd Ave S, Birmingham, AL 35294-3360, USA.
Differences among ethnic and racial groups in obesity-related traits have been clearly established in the scientific literature. To explore the genetic component underlying these differences, the genetic admixture approach has been used. In this approach, ancestry informative genetic markers are used to estimate a quantitative value representing the degree of ancestral background in individuals of admixed genetic background. Genetic admixture has been successfully used to explain racial and ethnic variation in obesity related traits; however, the understanding and measure of cultural and environmental components that also influence these phenotypes still requires further exploration.
An endorsement from Jonathan Pritchard:
Am J Hum Genet. 2004 Sep 22;75(5).
Statistical Tests for Admixture Mapping with Case-Control and Cases-Only Data.
Montana G, Pritchard JK.
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Admixture mapping is a promising new tool for discovering genes that contribute to complex traits. This mapping approach uses samples from recently admixed populations to detect susceptibility loci at which the risk alleles have different frequencies in the original contributing populations. Although the idea for admixture mapping has been around for more than a decade, the genomic tools are only now becoming available to make this a feasible and attractive option for complex-trait mapping. In this article, we describe new statistical methods for analyzing multipoint data from admixture-mapping studies to detect "ancestry association." The new test statistics do not assume a particular disease model; instead, they are based simply on the extent to which the sample's ancestry proportions at a locus deviate from the genome average. Our power calculations show that, for loci at which the underlying risk-allele frequencies are substantially different in the ancestral populations, the power of admixture mapping can be comparable to that of association mapping but with a far smaller number of markers. We also show that, although "ancestry informative markers" (AIMs) are superior to random single-nucleotide polymorphisms (SNPs), random SNPs can perform quite well when AIMs are not available. Hence, researchers who study admixed populations in which AIMs are not available can perform admixture mapping with the use of modestly higher densities of random markers. Software to perform the gene-mapping calculations, "MALDsoft," is freely available on the Pritchard Lab Web site.
http://pritch.bsd.uchicago.edu/
I think what you are saying is that DNAP is somehow precluded from competing in the personalized medicine arena due to developments such as the one you reference. However, there is a difference between developing and implementing platform components (including standards) and offering value added services that will utilize that platform. I think it is in the latter area that DNAP will come into its own.
How about this one:
Grant Number: 1R01GM069890-01A1
PI Name: MARJORAM, PAUL
PI Email: pmarjora@usc.edu
PI Title:
Project Title: Computational Methods for Fine Mapping
Abstract: DESCRIPTION (provided by applicant): We propose to continue work on the use of computationally intensive methods to fine-map genes involved in complex traits. This work was previously supported under our grant "'Computational methods in genetic epidemiology" (GM58897, PI: D. Thomas). The present incarnation is a more focused version of this earlier grant. Our particular emphasis is on methods that exploit the underlying genealogy (ancestry) of a sample of interest. The pattern of haplotype diversity, D, one sees in a sample of individuals is the result of a complex interaction between the unobserved genealogy, G, of the sample (which itself is a function of recombination) and the forces of mutation acting upon that genealogy. This is further influenced by the shared ancestry induced by the presence of the functional mutation(s) related to the trait of interest. This results in linkage disequilibrium in regions close to functional mutations. In principle, one wishes to explore the space of possible genealogies that might give rise to a particular data set and use this as a basis for an approach to mapping. Such an approach is likely to be impossible, or prohibitively expensive computationally. We therefore propose to adopt the following two approximations to this desired goal: - Genealogical methods in which we explicitly include the unobserved genealogy of the sample of interest, but use hybrid rejection/MCMC methods to avoid calculating P (DIG), (this quantity can only be calculated for a family of simplistic, unrealistic mutation models). - Bayes methods, which abstract out the effects of the genealogy using hierarchical clustering techniques.
Thesaurus Terms:
computational biology, computer assisted sequence analysis, epidemiology, family genetics, genetic mapping, method development
human population genetics
bioinformatics, clinical research, human data, statistics /biometry
Institution: UNIVERSITY OF SOUTHERN CALIFORNIA 2250 Alcazar Street, CSC-219 LOS ANGELES, CA 90033
Fiscal Year: 2004
Department: PREVENTIVE MEDICINE
Project Start: 01-SEP-2004
Project End: 31-AUG-2008
ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
http://www.usc.edu/programs/pibbs/site/faculty/marjoram_p.htm
This researcher seems to have some common areas of interest:
Grant Number: 5U01DK062413-03
PI Name: YANG, HUIYING
PI Email: huiying.yang@cshs.org
PI Title: ASSISTANT PROFESSOR AND ASSOCIATE
Project Title: Mapping genes for IBD by admixture LD in Puerto Ricans
Abstract: DESCRIPTION (provided by applicant): Studies by the genome scan approach have identified over 10 chromosomal regions containing putative loci predisposing to IBD. The identified IBD1 gene (NOD2) can only explain a small percent of Crohn's disease (CD) patients and does not contribute to ulcerative colitis (UC). Thus, other genes that contribute to IBD susceptibility exist and need to be identified. Compared to the NOD2 gene, the remaining loci contribute a lower susceptibility to IBD as indicated by weaker linkage evidence and less consistency across populations/studies. To identify such genes with modest effects, association studies based on linkage disequilibrium (LD) are the method of choice. However, in the Caucasian population the extent and usefulness of LD is limited by population history. Therefore, we herein propose an alternative strategy to map the IBD genes by taking advantage of an admixed population in Puerto Rico - mapping by admixture linkage disequilibrium (MALD). The goal of this study is to identify IBD susceptibility genes by narrowing selected chromosome regions showing sufficient evidence for linkage, then performing fine mapping using both case-control and the family based approaches. Specifically, the investigators will establish a panel of clinically characterized Puerto Rican IBD patients (300UC, 300CD, 300control) and families (400 trios); narrow selected chromosomal regions containing putative loci for IBD using MALD with population specific markers; evaluate potential interaction/confounding effect with NOD2 and serological antibodies (ANCA, ASCA, I2); and fine map the susceptibility genes with dense markers across the narrowed region and within candidate genes. By covering important chromosomal regions, using an admixed population in which LD has been sustained at longer chromosome segments; genotyping sufficient population specific markers; controlling for spurious association; evaluating interaction effects with other factors, and employing a two-stage mapping strategy, this proposal maximizes the opportunity to refine the chromosomal regions that contain susceptibility genes for IBD, thus enhancing the opportunity to identify the actual genes that contribute to the development of IBD.
Thesaurus Terms:
Puerto Rican, gene expression, genetic mapping, inflammatory bowel disease, linkage disequilibrium
chromosome, clinical trial, cooperative study, gene mutation, genetic marker, genetic susceptibility, genotype, quantitative trait loci
clinical research, human subject
Institution: CEDARS-SINAI MEDICAL CENTER BOX 48750, 8700 BEVERLY BLVD LOS ANGELES, CA 900481804
Fiscal Year: 2004
Project Start: 30-SEP-2002
Project End: 30-JUN-2007
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
http://www.csmc.edu/4017.html
Director, Genetics Epidemiology
Huiying Yang, MD, PhD is Director of the Genetic Epidemiology Program for the Medical Genetics Institute at Cedars-Sinai. Dr. Yang is also an associate professor of pediatrics an associate professor of epidemiology at the David Geffen School of Medicine at University of California, Los Angeles (UCLA), and she is a guest professor at the School of Public Health, Peking University, Health Science Center.
Dr. Yang's primary areas of research interest involve genetic and environmental risk factors for several common complex diseases. She leads several National Institutes of Health (NIH)-funded research projects, including projects to: map genes for inflammatory bowel disease in Caucasian populations using linkage and linkage disequilibrium approaches; use a mapping by admixture linkage disequilibrium approach to identify susceptibility genes for inflammatory bowel disease in the Puerto Rican population; study host genetic predisposition which determines an individual's response to interferon-related therapy among HCV infected patients; and map genes for keratoconus. In addition, she leads analytic efforts in two other multi-center projects - a program project of mapping genes for insulin resistance in a Mexican-American population, and a pharmacogenetics study of ACE inhibitors and statins in Caucasian and African-American populations.
Dr. Yang is a member of numerous professional organizations, including the American Society of Human Genetics, Society for Epidemiologic Research, International Epidemiological Association, International Genetic Epidemiology Society, American Gastroenterological Association and the American Diabetes Association. She has served on several NIH-sponsored research steering committees and has published numerous genetic epidemiology research reports and review articles.
After graduating from Beijing Medical University (now Peking University, Health Science Center), she started her postgraduate training in genetic epidemiology with Drs. C.S. Chung and Newton Morton at the University of Hawaii. When she completed her doctorate degree program, she started postdoctoral training at the Medical Genetics Institute at Cedars-Sinai.
Banking on solving crime
http://www.canoe.ca/NewsStand/EdmontonSun/News/2004/09/21/637331.html
The DNA data bank in Ottawa has 64,608 criminal profiles, but as
the Sun found out, police feel the number excludes too many while libertarians argue the danger of the bank having them at all.
The fingerprint examiner gingerly opens another Purolator bag containing DNA samples from some of the most violent criminals in the country.
Instead of their photos being posted on some national wall of infamy, the prisoners' genetic signatures are about to be uploaded into the four-year-old National DNA Data Bank, where they will be matched now and in the future against DNA taken from thousands of unsolved crimes. Getting away with murder just got infinitely more difficult.
Housed at RCMP headquarters, the databank is a place of pass cards, strict security and crime-fighting zeal.
At its head is Dr. Ron Fourney, a world DNA expert with a sense of humour. When his local sub shop made him a sandwich containing a hair, he warned the staff that he'd be back to a take a DNA sample from each of them to find out whose it was.
He had to reassure them he was just joking.
The NDDB is his baby and he's obviously proud of his staff and the job they do.
"When they leave at the end of the day, they've made a difference," he says, as he offers a tour of the state-of-the-art facility.
"They've linked serial crimes together, they've exonerated an innocent individual, they've helped to provide closure to a victim and they've contributed to making safer communities across Canada. It's a pretty heady job description."
In the lab, robotic work stations process multiple trays of 96 DNA samples at a time with offender profiles developed and sent to the database within a swift three to five days.
A computerized system developed by the RCMP tracks each criminal's DNA sample at every step as it is extracted, amplified and digitized, creating an audited "chain of evidence" to deflect any challenges by defence lawyers in court.
SOLVED 154 MURDERS
"It double-checks everything I do," says DNA analyst Allison Desroches.
There are now 64,608 DNA criminal profiles entered into the NDDB's Convicted Offender Index and 16,448 profiles of unknown DNA in its Crime Scene Index.
At the end of each day, Sylvain Lalonde runs the computer program which cross-checks the two databases. They used to ring a cowbell when each "hit" linking the two was recorded. "Once we got to 1,000," Lalonde smiles, "we stopped ringing the bell."
The NDDB is now credited with helping to solve more than 2,000 crimes, including 154 murders. The first killer it would snag was Richard Mark Eastman.
The horrific murder case had gone unsolved for nine years. Muriel Holland, 63, was a playwright, model and former U.S. ambassador to Mexico who had just moved her 93-year-old father into her Mississauga seniors home.
Shortly after 1 a.m. on Aug. 27, 1991, Eastman broke into her ground-floor apartment and found Holland sleeping on a pullout sofa. He raped and strangled her, twisting a dish towel around her neck while her elderly father slept in the next room.
Peel Regional Police found a partial fingerprint and semen on the body that led to a DNA profile of the killer. But the case went no further and her family gave up hope the murder would be solved.
But, just a few months after the NDDB was officially opened in November 2000, Peel police sent in their DNA profile of Holland's rapist.
On May 4, 1991, a DNA sample from Eastman, who had been convicted of sexual assault in 1995, was forwarded to the convicted-offender database.
On that very day, the data bank linked Eastman's DNA to the Holland murder scene. Eastman became the first person charged with murder as a result of the new NDDB.
One of its newest areas is uploading DNA fingerprints from break-and-enter crime scenes. "We're finding that 15% are linked to some of our most serious crimes," Fourney says.
Despite its success, the police want more.
Investigators are frustrated by the number of offenders not eligible for the database - for example, murderers who killed before the data bank was created in June 2000 do not have to submit a DNA sample unless they have killed more than once, at different times.
Last year an Ontario judge ordered the destruction of DNA samples taken from two murderers convicted before 2000 because, although they had killed several people each, the murders had occurred at the same time.
The unsolved slayings of Erin Gilmour and Susan Tice are glaring examples of where Toronto police believe a more comprehensive data bank could finally uncover an elusive serial killer.
KILLED BY SAME MAN
Five days before Christmas 1983, Gilmour, 22, was raped and stabbed to death in her fashionable Yorkville apartment. A few months earlier, Tice, 45, a social worker and mother of four, was stabbed to death in her Grace Street home. Other than the cause of death, nothing else tied the two murders together.
However, during the cold-case review of 2002, with technology now available to test the DNA left at both scenes, Toronto Police discovered the two had actually been killed by the same man.
It remains unsolved but Supt. Gary Ellis has his theory.
"Given that it was a sex murder and he's murdered six months apart, suspect profiling would indicate that this person wasn't going to stop," says Ellis, who investigated the Gilmour case as a young detective.
"However, no offender DNA matches, no crime-scene matches have come back. Those murders have stopped.
"Perhaps that person was arrested for another offence and is currently sitting in a penitentiary and he's out of our reach. We can't go into the penitentiary and take DNA because they say a person has to be convicted of two separate murders or be declared a dangerous offender or has committed two sexual assaults ...
"If that person who killed Susan Tice and Erin Gilmour was arrested for another murder, he might be sitting doing 25 years right now, yet these murders go unsolved, their families have no closure and we have no way of getting to the person. Essentially, they're being protected in prison."
And then there is the killer of 11-year-old Alison Parrott. Francis Carl Roy was arrested and convicted based on DNA evidence, and yet he is not in the DNA data bank.
"It took 11 years between the time he murdered her and he was arrested," Ellis says. "This type of offender, they don't do it once and that's it. Yet he's not in the DNA data bank.
"We don't know what he did before killing her. We don't know what he did after killing her until the time he was arrested. We have no way of telling what he has done."
That is why Ellis wrote an internal report recommending the national database be expanded to include more convicted offenders.
This summer, Toronto police Chief Julian Fantino and London's deputy chief called for the power to take DNA samples automatically upon arrest, just as fingerprints are taken now.
It's been common procedure since April in the United Kingdom - home of the world's first and largest database which now tops 2.5 million DNA profiles - as well as in many parts of the U.S.
Civil libertarians, however, are vehemently against the proposal and are worried about our DNA future.
DNA, they argue, holds much more sensitive personal information than fingerprints do and could easily be misused.
Insurance companies, for example, may one day demand access to discover if the holder has a certain gene specific to cancer.
Police may want to know if a person's DNA contains a "violence gene" or a "sex offender gene." It sounds like science fiction, but then, who dreamed 20 years ago that we might use chewing gum to find a killer?
'JUNK DNA'
The DNA experts insist we have nothing to fear.
At the NDDB, the only parts of DNA which are profiled and stored on the database are 13 areas known as "junk DNA" - they vary from person to person, but contain no data about a person's looks, health or any other personal characteristic.
"The deal we forged with Canadians was that the markers we use are anonymous snapshots that don't encode for any physical or mental attributes," says Fourney, the officer in charge.
"The only minor exception is that we do gender discrimination - we can tell if the sample is from a male or female. Because of the sheer power of the science, that's what we've limited ourselves to looking at."
Privacy is guaranteed, he says, because the DNA profiles are securely stored as anonymous fingerprints identified only by a bar code number. "If you wanted me to pull up Paul Bernardo's DNA profile, I wouldn't have a clue. He's just as anonymous as the 70,000 other offender samples in the database."
Unlike Britain, Canada also destroys DNA profiles collected during investigations rather than adding them to the NDDB.
But for each DNA fingerprint they do store, Fourney admits the data bank retains a complete sample which has not been reduced to those 13 markers of impersonal information. What if that DNA fell into nefarious hands?
"We have the most stringent controls of anyone in Canada," he insists.
Can medical labs say the same? Most of us, he says, don't think twice when we have blood drawn each year for medical tests. "It's ironic. What happens to that blood sample? Millions are taken every year and we have no clue what happens to it."
If this brave new world of DNA were not complicated enough, Sir Alec Jeffreys, the scientist who discovered DNA typing, is now warning that it's not as infallible as we were led to believe. He's concerned there is an increasing danger of false positives as the use of the technique becomes more widespread.
When scientists develop a DNA fingerprint, they're taking just a snapshot of the DNA, not the whole picture. Jeffreys says that the U.K. standard of comparing 10 markers in the DNA is no longer foolproof - Canada and the U.S. use 13 - and must be more sophisticated.
If not, there could be more frightening cases like that of Raymond Easton. In 1999, the 49-year-old British man suffering from advanced Parkinson's disease became the first recorded case of mistaken DNA identity when he was charged with a burglary 300 km away from his home.
The U.K. data bank had matched a DNA sample he'd given in a family dispute four years before to that taken from the crime scene. Though he was obviously disabled, charges were only dropped after a more advanced DNA test
"This should be very alarming," warns Toronto criminal lawyer Ricardo G. Federico. "If DNA is the best thing to happen to forensic science, why is there an increasing danger of false positives? The scientists should hang their heads in shame."
Jeffreys' solution would be to log everyone's DNA into a confidential data bank from birth.
It's a view shared by Greg Parsons, the Newfoundland paramedic wrongly convicted of murdering his mother. "If you do the crime and your DNA is there, you should go to jail. And it could stop crime; It's a deterrent in itself."
His lawyer disagrees. While DNA cleared Parsons, Jerome Kennedy recently won a murder case after proving the DNA against his client had been tainted.
"DNA is a science that appears to be unquestionable, but what we have are human beings collecting the samples and human beings testing the samples," the lawyer cautions. "With human beings, there's always the possibility of a mistake."
Fourney is quick to remind us that solving crimes takes more than just a DNA match. "It usually just points the finger," he says. "It's the smoking gun to allow investigators to zero in."
That investigative tool is advancing at dizzying speed. Canadian scientists are working on extracting DNA from fingerprints. Eventually, Fourney predicts, biochips will allow the miniaturization of the process so that it can be taken directly to the scene of the crime. DNA results may one day be produced within minutes rather than in hours, giving police instant leads.
Unlike the NDDB, other forensic bodies are keen on developing more personal profiles from suspect DNA. In Britain, a genetic Sherlock Holmes can now examine DNA left at a crime scene and tell investigators their suspect's ethnic ancestry as well as if he's a redhead.
In the near future, bio-sleuths hope to be able to describe a criminal's age, eye colour and facial features just from examining a pin-sized dot of blood.
FORENSIC INEPTITUDE
The ethical implications of it all are a little disconcerting. Once that information can be determined, how long before Canadian police demand it as well? Should authorities have access to such personal information? What about foreign governments?
DNA profiles are now being exchanged by police forces around the world. Do we trust their standards? Should Canadians be arrested based on their DNA matching a crime scene in Texas, a state currently plagued by a scandal of forensic ineptitude?
And finally, in the interests of fighting crime, are we willing one day to have the genetic secrets of who we are and what we might be, logged onto some universal DNA database?
"Where is this all taking us?" wonders Federico, the criminal attorney.
Nowhere we don't want to go, insists Fourney. Next year, the NDDB will be subject to a five-year parliamentary review where the safeguards we want can be debated anew.
In the meantime, his data bank computers continue to cross-match thousands of DNA fingerprints, silently searching for criminals who thought they could get away scot-free.
- michele.mandel@tor.sunpub.com.
Forthcoming Content
The list below details the articles which have been accepted for publication in future issues of Journal of Medical Genetics
http://jmg.bmjjournals.com/future/
Relation of type 2 diabetes to individual admixture and candidate gene polymorphisms in the Hispanic-American population of San Luis Valley, Colorado
Esteban J Parra, Clive J Hoggart, Carolina Bonilla, Sonia Dios, Jill M Norris, Julie A Marshall, Richard F Hamman, Robert E Ferrell, Paul M McKeigue, and Mark D Shriver
Not sure if this was posted previously:
http://criminaljustice.state.ny.us/forensic/trainingandfunding.htm
Trends in Forensic DNA Technology
November 9, 2004 9:00 AM – 4:30 PM
NYSP AND SUNY EAST CAMPUS
9:00 – 9:45 Texas Missing Person Program
Speaker / University of North Texas
9:45 – 10:30 Current Legal Issues
Speaker / NYSP
10:30 – 10:45 BREAK
10:45 – 11:15 CODIS Update
11:15 – 11:45 QIAGEN Validation for Casework
Speaker / Westchester Co.
11:45 – 12:45 Lunch
12:45 – 1:15 GENEMAPPER ID Validation
1:15 – 1:45 Validation of ROCHE Linear Array MT DNA HVI and II Region Specific Typing Kits
Speaker / NYC-OCME
1:45 – 2:30 Y PLEX Y STR KIT
Speaker / PROMEGA
2:30 – 2:45 BREAK
2:45 – 3:45 Voice Recognition & Serology Exam
Speaker / Kansas State Police
3:45 – 4:30 Race Determination Using DNA
Speaker / DNAPrint Genomics
Yes, our friends "down under" are getting a lot of attention these days:
http://thestar.com.my/news/story.asp?file=/2004/9/19/education/8853048&sec=education
New biotech hub
THINK Queensland and most people would think of beautiful pristine beaches and holiday fun.
However, Queensland is fast gaining a reputation for education and excellence in research, particularly in the field of biotechnology. The state currently attracts international students from over 120 countries around the world.
Australia’s “smart state” is active in research in major biotechnology-related disciplines such as genomics, molecular biology, microbiology, recombinant DNA technologies, drug discovery, biomedical engineering and bioinformatics.
Since 1998, the state government has invested more than AUD$2.4 bil (RM6.35 bil) in science, research, education and innovation initiatives. This has paved the way for the development of world-class facilities which offer students unrivalled opportunities in the field.
Students also get to study in some of Australia’s largest research facilities, mix with academics and students from diverse cultures and backgrounds, and participate in leading edge research in fields ranging from medicine to agribusiness.
The state is also involved in various major research projects. This includes a bio-prospecting project by the University of Queensland to develop an environmentally-sustainable drug discovery process, the cultivation and harvesting of nerve cells for spinal cord regeneration by Griffith University, and research into insect-transmitted diseases such as dengue fever which resulted in the successful mapping of the complete genome of the Wolbachia bacteria.
Besides being home to one of the largest medical research facilities in Australia, Queensland also has one of the largest concentrations of tropical marine scientists in the world as well as a creative industries precinct renowned for education in film, arts, design and e-commerce.
A leader in telemedicine, distance education and e-learning, it also has more than 30 research centres driving innovation in fisheries, forestry, satellite communications, environmental management and sustainable tourism education.
Another feather in its cap is its electronic games industry. It has one of the largest electronic games industry clusters in Australia and the second largest e-security cluster in the world, after North America.
Given Malaysia’s interest in biotechnology and recent forays into the field, and the fact that both Malaysia and Queensland share unique biodiversity and common economic goals, there is indeed tremendous potential for cooperation between Malaysian students and the university in the near future.
Another one:
J Invest Dermatol. 2004 Oct;123(4):760-762.
Epidermal Growth Factor Gene (EGF) Polymorphism and Risk of Melanocytic Neoplasia.
James MR, Hayward NK, Dumenil T, Montgomery GW, Martin NG, Duffy DL.
Queensland Institute of Medical Research, Brisbane, Australia.
A common single nucleotide polymorphism (SNP) in the 5' untranslated region (5'UTR) of the epidermal growth factor (EGF) gene modulates the level of transcription of this gene and hence is associated with serum levels of EGF. This variant may be associated with melanoma risk, but conflicting findings have been reported. An Australian melanoma case-control sample was typed for the EGF+61A>G transversion (rs4444903). The sample comprised 753 melanoma cases from 738 families stratified by family history of melanoma and 2387 controls from 645 unselected twin families. Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling and pigmentation phenotype. SNP genotyping was carried out via primer extension followed by matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectroscopy. The EGF+61 SNP was not found to be significantly associated with melanoma status or with development of nevi or freckles. Among melanoma cases, however, G homozygotes had thicker tumors (p=0.05), in keeping with two previous studies. The EGF polymorphism does not appear to predispose to melanoma or nevus development, but its significant association with tumor thickness implies that it may be a useful marker of prognosis.
Even the Malaysians are having a go:
J Hum Genet. 2004 Sep 11
Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations.
Cha PC, Yamada R, Sekine A, Nakamura Y, Koh CL.
Institute of Biological Sciences (Genetics and Molecular Biology), Faculty of Science, University of Malaya, 50603, Lembah Pantai, Kuala Lumpur, Malaysia.
The extensive nucleotide diversity in drug-related genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.
That would be this Dr. Chong Lek Koh of the University of Malaya. You can find a bit more information about him here:
http://www.investorshub.com/boards/read_msg.asp?message_id=2427482
Not convinced? Here's another application of the technology:
Hum Mol Genet. 2004 Sep 14.
Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM).
Wang H, Parry S, Macones G, Sammel MD, Ferrand PE, Kuivaniemi H, Tromp G, Halder I, Shriver MD, Romero R, Strauss JF 3rd.
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. We identified three single nucleotide polymorphisms (SNP) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM). The minor alleles +17 (G) and -381 (G) were in complete linkage disequilibrium. A promoter fragment containing the three minor alleles had 3-fold greater activity in chorion-like trophoblast cells (BeWo, JEG-3, HTR-8/Svneo) compared to the major allele promoter construct. Electrophoretic mobility shift assays revealed differences in BeWo nuclear protein binding to oligonucleotides representing the -381 and -799 SNPs, suggesting that the minor alleles have reduced transcription factor binding. A case-control study of African-American neonates using allele-specific primers revealed a statistically significant association between the three minor allele haplotype, which displays the highest MMP8 promoter activity in trophoblast cells, with PPROM with an odds ratio of 4.63 (p<0.0001), whereas the major allele promoter appeared to be protective (odds ratio=0.52, p<0.0002). None of the minor alleles were individually associated with PPROM. These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes.
Everybody's at it:
J Hum Genet. 2004;49(9):495-9.
Genetic background of people in the Dominican Republic with or without obese type 2 diabetes revealed by mitochondrial DNA polymorphism.
Tajima A, Hamaguchi K, Terao H, Oribe A, Perrotta VM, Baez CA, Arias JR, Yoshimatsu H, Sakata T, Horai S.
Department of Biosystems Science, The Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa 240-0193, Japan.
People in the Dominican Republic are considered to be genetically heterogeneous owing to the post-Colombian admixture of Native American, African, and European populations. To characterize their genetic background, nucleotide sequences of the D-loop region of human mitochondrial DNA (mtDNA) were examined in 33 healthy women and 50 gender-matched patients with obese type 2 diabetes (OD) from the Dominican Republic. Phylogenetic analysis of 198 mtDNA lineages including Native Americans, Africans, and Europeans enabled us to assess relative genetic contributions of the three ancestral fractions to the two groups in the Dominican Republic. In the OD group, the majority (64.0%) of the mtDNA lineages were from African ancestry, whereas the Native American fraction was predominant (51.5%) in the healthy group, with both showing smallest amounts (14.0% and 9.1%, respectively) of European contribution. This difference in maternal genetic background between the two groups was similarly demonstrated by phylogenetic analysis at the population level based on net nucleotide diversities between populations. These findings may imply ethnic-specific predisposition to OD, a possible association of an unidentified factor from African ancestry with OD in the Dominican Republic population.
Arch, let's hope you are the exception as I look forward to meeting you one of these years at a shareholders meeting! The various groups involved in research really do seem to be making some headway, and it is always nice to see that people find ancestry relevant to their efforts.
Talking of old things:
http://jmg.bmjjournals.com/cgi/content/full/39/12/913
SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family
Journal of Medical Genetics 2002;39:913-915
S Chen1,2, M K Chung2, D Martin2, R Rozich2, P J Tchou2 and Q Wang1,2
1 Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
2 Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Ancestry analysis (ANCESTRY 1.0) was performed for three family members in kindred QW1446 (II.1, II.3, and II.5 in fig 1A) by DNAPrint Genomics (Sarasota, FL). ANCESTRY 1.0 facilitates the estimation of biogeographical ancestry on three axes, Native American, West African, and European. In this analysis each subject was genotyped for 31 Ancestry Informative Markers. Using maximum likelihood, the individual ancestral proportions of these three populations in the resulting multilocus genotype was computed.10
http://www.lerner.ccf.org/moleccard/wang/
frog, no I disagree. eom
Frog, yes a masterpiece of logic based on a set of assumptions that are not at all tenuous or biased! To be fair, this line of reasoning occurred to me the first time I saw the event description. However, there are alternative explanations. For instance, Dr. Kondragunta's Attorney could have made a Motion to Withdraw as Plaintiff's Attorney for any number of valid reasons; or perhaps based on the fact that they did not think Dr. Kondragunta had a hope in hell of successfully defending the action or winning his countersuit, and therefore any renumeration based on a split of damages awarded to him would not be forthcoming - ample reason for any Attorney to cobble together grounds for a Motion to Withdraw and for a competent judge to throw said motion out. Then again, that is just speculation on my part of course.
In regards to a later response, pertaining to the reason the lawsuit was originally brought by DNAP, I contend that preventing posts to RB was not the primary motive. Rather, as you might recall from the Court documents which were viewable over the Internet at the time, the motivation related to actual or potential disclosure of company confidential information to third parties.
I am not sure if we will even see a full explanation of events at the point that the case is concluded, unless of course one of the Sarasota residents physically goes to the Courthouse to examine the details in situ...
Frog, there is an alternate view that might suggest that Dr Kondragunta has been wrongly advised, and has parted with a lot of his money defending a case that he cannot possibly win. I am sure that the truth lies somewhere between these two extremes (or perhaps between some other extremes). Time will tell...
BTW, which side do you think made the motion to withdraw (which was subsequently denied)?
There has been another little flurry of activity in the civil case against Dr Kondragunta, culminating in an appearance yesterday:
8/18/2004 MOTION - AMENDED/SUPPLEMENTAL (ATTACHMENTS)
8/18/2004 NOTICE OF HEARING
8/20/2004 NOTICE - DEPOSITION
8/30/2004 NOTICE OF HEARING - AMENDED
8/30/2004 NOTICE OF APPEARANCE
8/31/2004 NOTICE OF FILING (ATTACHED AFFIDAVIT)
9/9/2004 COURT APPEARANCE RECORD
On 27 October this case will have been going on for a year. I would think that somebody is racking up a lot of legal costs...
Grateful, thanks. Fascinating article (I couldn't stop thinking about it today while hiking in the mountains in the rain). Mark Shriver (amongst other things, Akey was his student for those that do not know) has often hinted that evolution was important. Now we see why potentially:
"...identifying regions of the human genome that have been the targets of natural selection will provide important insights into recent human evolutionary history – and may also help us understand and identify the genetic contribution to various complex diseases."
Or more succinctly:
"...finding genes that have been affected by natural selection may also help us find complex disease genes."
And the key to all this seems to be biogeographical ancestry. The collaborators on this are interesting as well. Akey, Nickerson, Kruglyak et al have all appeared several times before. Here are some examples:
http://www.investorshub.com/boards/read_msg.asp?message_id=1305802
http://www.investorshub.com/boards/read_msg.asp?message_id=2080656
http://www.investorshub.com/boards/read_msg.asp?message_id=1388988
I also have a feeling that there might be something else about AIMs and/or population structure/sub-structure that is important, and that we are not yet aware of. But hey...
I know that somebody posted this link recently, but it is worth repeating it as the comments by Tony Frudakis are worth (re)reading:
http://dienekes.blogspot.com/2004/08/euro-dna-test.html
Here are some (large) excerpts of Tony's posts (the others are interesting as well):
PART I – I dont mean to infiltrate your group here - I want you and every one else to discuss the test objectively as you seem to do, without interference from us here at DNAPrint - but I thought I could add something here just this one time. In reference to the choice of population model - we did in fact use Pritchard's STRUCTURE on a pan-European collection of samples to define the most appropriate population model for the bulk of Europeans. With k=4, our results were very similar to Rosenbergs, except we did not include the population isolates for obvious reasons (i.e. they are isolates, and therefore by definition not representative of the bulk of Europeans). By the way, we also used Principle Components Analysis like Cavalli-Sforza did, (reviewd in Joblings 2004 textbook), and got the same result - most of the variation is in a northwest to southeast orientation. (cont'd part II)
PART II - STRUCTURE broke the samples out into this same orientation, as shown on the website for the product, and the NOR and SA groups at the polar extremes of this range are associated with anthropometric traits (iris color) (also shown on the website). I think that speaks for itself. On top of this, the predominant archaeological clines are in the northwest to southeast orientation, as are classical blood group and Y-chromosome haplogroup distributions. Clearly, most of the genetic variation is distributed throughout Europe in this orientation. Maybe in the future we can make the test more complex by adding more populations and more markers to capture the second and third principle components of variation. We actually have this data and these markers - but it is not a practical test yet. Larger, more complex population models require more markers however, so it would be a much more expensive test. (cont’d part III).
Part III - You have to start somewhere so we started with the the principle component
As for excluded groups - not only did we not include the Basques, butwe also did not specifically include the Sardinians, nor the Roma, though the spread of the latter throughout Europe likely impact the distribution of ancestry we have so far observed (such as the high percentage in Iberia, where the Roma were known to settle en masse). We are actually testing how the Basques type as of this week, but Im afraid nobody could possibly know what to expect here. Basque and Sardininan ancestry must be the 9th and 10th or even greater principle components of variation in Europe (Im being facetious, but the point Im making is clear). Due to their supposed paleolith connections, should they type of more "NOR" or would STRUCTURE kick them out into their own group with our markers as it did for Rosenberg? Is the EURO-1.0 population model completely inappropriate for them? (contd part IV)
Part IV - With the chosen population model of EURO 1.0, they will type based on their genetic distance to each of the 4 groups. If the genetic distance to the closest group is still very large, we can say the model is inappropriate for this population. Similarly, it would also be inappropriate for a 100% sub-Saharan African, who could insist on taking the test and would be shoe-horned into the 4 EUropean groups even though they are not European and have no European admixture. For this reason, since EURO 1.0 is a hierarchical test requiring a prior fit with the population model, we do our best to pre-screen customers for this fit. This is why Ancestrybydna 2.5 is required. Unfortunately for Basques, this screen is impossible, and their ancestry would be shoe-horned into the NOR, MED, MIDEAS, SA model. However, unlike sub-Saharan Africans, the genetic distance between Basqueness and NOR/MED is almost certainly (cont’d part V)
Part V very low, and the test would therefore be reporting a more ancient connection than for most other EUropean customers. After all, EEuropean paleoliths and neoliths once shared a common non-African ancestor, did they not?
Icelanders are another isolate, with Scottish and Scandinavian roots, who type mainly with NOR ancestry with EURO-DNA 1.0. In this case, we know this is the expected result. The data for the Basques and Icelanders should be on the website soon.
Cheers and thanks for thinking about our science. Continue to critisize, evaluate, and think - good job to you all. I believe this is the most sophisticated discussion of our technology available other than from us and in the scientific literature.
Tony Frudakis
Scoob - that is an interesting analysis. Ill pass that on to Paul McKeigue and Mark Shriver and see what they think - they are two of the premier thought leaders in the field of molecular anthropology, and our close collaborators. Ill come back with their reactions if you like.
Part III - Hilde – I wonder if the Galicia were recent offshoots of more northerly populations compared to other neighboring ethnicities? This is the type of question I believe our test is well suited for. But as Dianekes suggests, there is plenty to think about when interpreting the test results. I cannot monitor the discussion daily, so I will trust that if there is a question of significance related to the test, or some confusion on the theory, perhaps Dianekes can email me so that I can provide my input. From my experience here, it is clear to me I need to reword part of the website so that our method of developing the test is more clear. As soon as we get the data on the Basques and Icelanders, we will post them and Id be happy to interpret with you folks if emailed. I just wanted to stop in and provide some input these first days the test is out.
Some interesting insights. The comment about testing the Basques "this week" was dated 31st August so it is very current.
OT Retro, funny thing but the hacking attempts seem to have stopped all of a sudden...
"Powered by Affymetrix", has a nice ring to it...
DNAP paper in Journal of Forensic Sciences cited in Celera patent application:
United States Patent Application 20040166519
Genetic polymorphisms associated with stenosis, methods of detection and uses thereof
Assignee Name : APPLERA CORPORATION
[0280] Furthermore, Tables 1-2 also provide population group (interchangeably referred to herein as ethnic or racial groups) information coupled with the extensive allele frequency information. For example, the group of 39 individuals whose DNA was re-sequenced was made-up of 20 Caucasians and 19 African-Americans. This population group information enables further refinement of SNP selection for human identification. For example, preferred SNPs for human identification can be selected from Tables 1-2 that have similar allele frequencies in both the Caucasian and African-American populations; thus, for example, SNPs can be selected that have equally high discriminatory power in both populations. Alternatively, SNPs can be selected for which there is a statistically significant difference in allele frequencies between the Caucasian and African-American populations (as an extreme example, a particular allele may be observed only in either the Caucasian or the African-American population group but not observed in the other population group); such SNPs are useful, for example, for predicting the race/ethnicity of an unknown perpetrator from a biological sample such as a hair or blood stain recovered at a crime scene. For a discussion of using SNPs to predict ancestry from a DNA sample, including statistical methods, see Frudakis et al., "A Classifier for the SNP-Based Inference of Ancestry", Journal of Forensic Sciences 2003; 48(4):771-782.
Miss Scarlet
Difficult to answer as there have been various estimated dates for these given in the past (some of which are covered by the PP confidentiality agreement). I personally would expect to see at least one at the end of this year or early in 2005.
Arch, from what I have read (and I am not an expert by any means) it looks as if they can potentially "solve" any complex trait. Some are more difficult than others (things like schizophrenia are often mentioned in this context), but I think unless I have missed something that the only thing stopping them is financial resources to undertake the R&D and associated clinical trials. If they can get one classisifer to market that should potentially solve this problem for them and enable them to dispense with La Jolla. Statinome and Ovanome are the keys here.
Using Genetic Admixture to Study the Biology of Obesity Traits and to Map Genes in Admixed Populations
Nutrition Reviews 1 July 2004, vol. 62, no. Supplement 1, pp. 69-74(6)
José R. Fernández[1]; Mark D. Shiver
[1] Division of Physiology and Metabolism, Department and Nutrition Sciences; Section on Statistical Genetics, Department of Biostatistics and Clinical Nutrition Research Center, University of Alabama at Birmingham, 1530 3rd Ave S, Birmingham, AL 352
Abstract:
Differences among ethnic and racial groups in obesity-related traits have been clearly established in the scientific literature. To explore the genetic component underlying these differences, the genetic admixture approach has been used. In this approach, ancestry informative genetic markers are used to estimate a quantitative value representing the degree of ancestral background in individuals of admixed genetic background. Genetic admixture has been successfully used to explain racial and ethnic variation in obesity related traits; however, the understanding and measure of cultural and environmental components that also influence these phenotypes still requires further exploration.
Keywords: RACIAL/ETHNIC DIFFERENCES; ANCESTRY INFORMATIVE MARKERS; GENETIC ADMIXTURE; OBESITY
A bit more information about Dennis Robbins:
http://www.geocities.com/~darobbins/
The share price may also rise if they are more buyers than sellers irrespective of revenues or expenditure. There are a whole host of other factors which could similarly affect share price. Que sera sera.
You are not saying anything that we don't know about. You are though saying it very often, hence the view that you doth protest too much...
The conference schedule for the Hugo Pacific conference (Genomic Medicine and Population Health) has been updated:
http://register.hugopacific.com/tt-demo.cfm
Medical Genomics: Human Variation and the Human Condition
(includes 2 Abstract presentations)
Tony Frudakis DNAPrint Genomics, Inc (USA)
Kuchan Kimm National Genome Research Institute (Korea)
Yuan-Tsong Chen Institute of Biomedical Sciences Academia Sinica (Taiwan)
Robert Williamson Institut Pasteur (Australia)
Eric Yap Defence Medical Research Institute (Singapore)
David Barker Illumina (USA)
The Karolinska Institute are aware of AIMs and MALD:
http://www.ki.se/info/vp/vp24-04.html
CGB Seminar
Ancestry and admixture mapping methods in the search for genes affecting complex disease risks
Mark Shiver, Ph. D.
Host: Dr. Anthony Brookes Center for Genomics and Bioinformatics, KI
Tid: 11 juni, 10.00
Plats: CGB Seminar Room (A-216), Berzelius väg 35, KI campus Solna
Elad Ziv is one of those names that keeps cropping up. He (amongst others) uses ancestry informative markers:
http://www.investorshub.com/boards/read_msg.asp?message_id=3043198
http://www.investorshub.com/boards/read_msg.asp?message_id=3040369
http://www.investorshub.com/boards/read_msg.asp?message_id=2810265
Look what was posted yesterday:
Grant Number: 1K22CA109351-01
PI Name: ZIV, ELAD
PI Email: eziv@itsa.ucsf.edu
Project Title: Breast Cancer, Breast Density & Admixture Among Latinas
Abstract: DESCRIPTION (provided by applicant): Breast cancer incidence rates vary widely among different racial and ethnic groups. Admixed populations, in which two or more ethnic groups have mixed, may provide insight into the etiology of these differences. Latino Americans are largely an admixed group descended from European, Native American, and African ancestors. In California, the majority of Latinos are immigrants from Mexico and Central American countries, and are mainly of European and Native American ancestry. Latinas have breast cancer incidence rates that are substantially lower than Caucasians but higher than Native Americans, consistent with their mixed European and Native American descent. This project will examine the association between genetic ancestry among Latinas and breast cancer risk. Using an established case-control study of Latinas in the Bay Area we will compare genetic ancestry among 240 Latinas with breast cancer and 300 age-matched Latina controls. Ancestry will be estimated with a series of genetic markers highly informative for ancestry. Analyses will be adjusted for known non-genetic risk factors for breast cancer. We will also examine the association between mammographic density and genetic ancestry among Latinas. Mammographic breast density is one of the strongest known risk factors for breast cancer and is a highly heritable trait. To address this aim we will recruit 100 Latina women with extremely high mammographic density and compare the genetic ancestry among these women with 100 Latina women with extremely low breast density. Based on these results we will determine whether genetic association studies of breast cancer risk and of mammographic density may be confounded by ancestry in the Latina population. In addition, this project will test the feasibility of using the increased linkage disequilibrium in admixed populations to identify genetic variations associated with breast cancer among Latinas.
Institution: UNIVERSITY OF CALIFORNIA SAN FRANCISCO 500 PARNASSUS AVE SAN FRANCISCO, CA 941222747
Fiscal Year: 2004
Department: MEDICINE
Project Start: 20-AUG-2004
Project End: 31-JUL-2007
Robert, the only "date" I can see is "Summer 2004", although on the event calendar there are two ELSI Summer Faculty Institute events on July 18th - 23rd and July 25th - 30th. I assume that is is one of these.
Here are some PowerPoint presentations from Dartmouth College Ethics Institute summer program:
http://www.dartmouth.edu/~ethics/2004/ppt/index.html
The last two mention DNAPrint enomics explicitly.
bag8ger, I don't think you will have too long to wait, although the patent application process does drag on...
bag8ger, I think it does more than that. Irrespective of share price considerations you can be sure that the developments at DNAP have not gone unnoticed. A couple of big steps for humankind...
If you want to post private messages feel free to do so. That is one indication of why I will not be sending you private messages or responding to your public messages in future.
"The validation and commercial implementation of RETINOME(TM) using this powerful approach is a historic event; RETINOME(TM) becomes the first test developed and validated for the inference of a complex genetics trait from DNA. Prior to the human genome era, complex genetics traits such as disease proclivity, drug response and particularly physical traits such as iris and hair color vexed geneticists for decades. The excitement generated by the completion of the human genome sequence draft in 2001 was based on the hope
that common human traits would finally be understood from a genetics perspective. The ultimate expression of genetic understanding is demonstrated by showing an ability to predict or infer a trait from DNA sequences, but so far this hope has remained largely unfulfilled. Prior to RETINOME(TM), no predictive genome-based test had been developed, described in the peer-reviewed literature or, most importantly, launched commercially.
I don't think it was so much a personal attack as an observation on your previous posts about not posting until 2005. Several other posters also commented on this. I do not think that any of these was a personal attack and will therefore not be removing any posts. If you feel that you wish to take this further please feel free to contact Matt. I would note that the disgusting sexist response of yours that I did remove has no place on this board or in polite company.