Contact: Jane E. Rubinstein
jrubinstein@rubenstein.com
212-843-8287
23andMe Inc.

Goal is highly scalable pharmacogenomics research

Mountain View, Calif. — 23andMe has launched a project funded by the National Institutes of Health (NIH) which is aimed at validating 23andMe’s highly-scalable platform for pharmacogenomics research. The company received $190,000 in stimulus funding from the American Recovery and Reinvestment Act of 2009 for “Web-based Phenotyping for Genome-Wide Association Studies of Drug Response” from NIH’s National Human Genome Research Institute.

“One of 23andMe’s research goals is to identify novel pharmacogenetic associations using web-based phenotyping of efficacy and toxicity,” said Anne Wojcicki. co-founder and CEO of 23andMe. “If this project is successful in yielding replications, it will set the stage for rapid, well-powered and cost-effective research on many mediations. In particular, it will facilitate research on new medications as they hit the market, serving to significantly advance personalized medicine.”

Building on 23andMe’s initial success in discovering novel genetic associations related to hair curl, asparagus anosmia (the inability to detect the scent of certain asparagus metabolites in urine), the photic sneeze reflex (the tendency to sneeze when entering bright light), and freckling, as published in PLoS Genetics this year, the research arm of 23andMe is now investigating genetic factors underlying responses to three classes of drugs: non-steroidal anti-inflammatory drugs (NSAIDs); protein-pump inhibitors (PPIs), used to treat gastroesophogeal reflux disease (GERD); and the blood thinner, Warfarin.

This project leverages 23andMe’s customized genotyping chip, which includes thousands of single nucleotide polymorphisms (SNPs) not included on standard chips. In particular, this chip tests numerous SNPs within genes known to be associated with drug metabolism, efficacy, toxicity, or other side effects.

The first phase of the study includes development and validation of web-based surveys to assess the drug side effects and drug effectiveness experienced directly by 23andMe’s customers. During the second phase, the research team will determine whether this approach enables them to replicate previously known associations between response to these three classes of drugs and variation within two genes: CYP2C9 and CYP2C19. 23andMe’s research team will also search for previously unknown genetic factors associated with response to these classes of drugs, taking into consideration a broad range of non-genetic factors such as age, sex, and body-mass index, among others.

In previous studies, 23andMe has demonstrated that self-reported information from customers yields data of quality comparable to that gathered using traditional research methods. Additional benefits of 23andMe’s web-based research model include: the ability to perform hundreds of studies in parallel; easy and efficient ways to contact individual participants multiple times and ask follow-up questions — this enables 23andMe researchers to quickly zero-in on associations that could be the building blocks for future research aimed at prevention, better treatments, and potentially cures for a multitude of diseases and conditions. A web-based research model also affords participants added flexibility, they can choose when and where to respond to surveys and may take breaks to check on answers to specific questions as needed. The geographic location of research participants and their proximity to a research center is no longer a limiting factor with a web-based approach, providing an even larger pool of potential research participants.

Ultimately, web-based data collection, parallel analysis of hundreds of traits and diseases, and highly automated genotyping lead to low cost research. 23andMe’s more than 60,000 customers are invited regularly to participate in a range of research projects; eligible and consenting customers will be invited to join this study during 2011.

The project described is supported by Award Number 1R43HG005807-01 from the National Human Genome Research Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Human Genome Research Institute or the National Institutes of Health.

Disclosures: 23andMe is also currently conducting a study related to Parkinson’s disease that involves web-based collection of phenotypic data.

About 23andMe

23andMe, Inc. is a leading personal genetics company dedicated to helping individuals understand their own genetic information through DNA analysis technologies and web-based interactive tools. The company’s Personal Genome Service enables individuals to gain deeper insights into their ancestry and inherited traits. The vision for 23andMe is to personalize healthcare by making and supporting meaningful discoveries through genetic research. 23andMe, Inc., was founded in 2006, and the company is advised by a group of renowned experts in the fields of human genetics, bioinformatics and computer science. More information is available at www.23andme.com.

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By Justin Petrone

BlueGnome this week acquired intellectual property for karyomapping technology in an effort to carve out a bigger chunk of the pre-implantation genetic-diagnostic market.

CEO Nick Haan said that karyomapping, which uses SNP genotyping to screen for genetic disorders in embryos, will complement BlueGnome’s 24sure offering, which relies on a bacterial artificial chromosome array and software to confirm that eggs and embryos contain the correct number of chromosomes prior to implantation in an in vitro fertilization cycle.

Cambridge, UK-based BlueGnome launched 24sure last year, and last month established a new company, called Sure Laboratories, also based in Cambridge, to support the service (BAN 9/7/2010).

“We aim to address diagnosis of single-gene disorders using SNP-array technology,” Haan told BioArray News this week. “Karyomapping is the first technique which enables single-gene testing sufficiently robustly for routine clinical use,” he said. “It also has advantages of determining inheritance patterns across the genome.”

BlueGnome acquired the karyomapping IP from inventor Alan Handyside and the London Bridge Fertility, Gynaecology, and Genetics Centre, where Handyside is the scientific director. As part of the deal, Handyside has joined BlueGnome as head scientist of pre-implantation genetics.

According to Haan, karyomapping relies on the ability to obtain SNP-genotype information from relatives, such as parents and grandparents, as well as those who are known to carry a deleterious gene. By matching the SNP genotypes of embryos to relatives, and knowing where the deleterious gene resides, it is possible to infer the status of the embryo, Haan said.

The firm’s ultimate goal is to use arrays and other technology to “significantly improve IVF success rates,” he said. The company’s 24Sure technology will in the future not only have the ability to screen eggs and embryos for aneuploidy, but also single-gene conditions.

“Karyomapping allows us to be able to offer a new product which can screen for single-gene disorders in single cells,” said Haan. He did not elaborate on when the new product will become available. Haan said that Sure Labs will use karyomapping in the future and that Handyside will eventually play a role in the new cytogenetic laboratory services firm, though “not at this stage.”

Handyside said in a statement that he joined BlueGnome because its “24sure platform has already established itself as the standard for screening the very large-scale chromosomal imbalances that are thought to be a major cause of infertility.”

The company now has an “opportunity to extend this approach to the inheritance of some truly debilitating genetic disorders,” he said in the statement.

PGD

Pre-implantation genetic diagnosis, or PGD, is used in combination with IVF approaches where there is a risk of severe genetic disorders being inherited from parents. PGD screening is used to identify embryos that do not carry defective genes and to identify those that can be safely implanted.

Current methods rely on PCR, though BlueGnome describes this approach as “expensive, time-consuming, and only available at a small number of very specialist laboratories.” Karyomapping, in contrast, is a genome-wide method that eliminates the need to develop specific PCR assays for each gene defect.

Handyside and colleagues described their approach in a recent Journal of Medical Genetics paper in which they used Illumina HumanCNV370 Infinium-II Quad and Duo BeadChips to establish genotypes of parents, siblings, or other appropriate family members. This information was used to identify informative loci for each of the four parental haplotypes across each chromosome and map the inheritance of these haplotypes and the position of any crossovers.

According to the authors, the resulting “karyomap” identifies the parental and grandparental origin of each chromosome and chromosome segment and is “unique for every individual being defined by the independent segregation of parental chromosomes and the pattern of non-recombinant and recombinant chromosomes.”

Karyomapping, the authors write, “enables both genome-wide, linkage-based analysis of inheritance and detection of chromosome imbalance where either both haplotypes from one parent are present or neither are present.”

The paper’s authors outline several “major” applications of their technology. One is for carriers of “balanced structural chromosome abnormalities, mainly reciprocal and Robertsonian translocations, which can cause infertility or repeated miscarriage.”

Another “important” application is for human leucocyte antigen matching, “with or without single gene-defect testing if required, with the aim of isolating cord blood stem cells at birth for transplantation to an existing child with a serious blood related illness.”

The authors do note a few drawbacks to the technique, such as the “relatively expensive” use of arrays when compared with standard methods, though they believe that arrays will ultimately help labs cut down on labor costs. They also cite “challenging clinical and ethical issues” inherent in using a genome-wide approach for pre-implantation genetic diagnosis, as counselors might be compelled to inform clients of de novo mutations that may be hard to interpret.

The authors suggest blinding the study to only look at information contained in the karyomap. “If deemed necessary, it would be straightforward to blind or remove some or all of the genotype data from clinical records,” they suggest.

Illumina has received US Patent No. 7,803,537, “Parallel genotyping of multiple patient samples.” The patent claims a method for the parallel genotyping, or other sample analysis, of multiple patients by direct sample immobilization onto microspheres of an array. The patient beads can then be used in a variety of target analyte analyses, according to the patent.

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Illumina has also received US Patent No. 7,803,751, “Compositions and methods for detecting phosphomonoester.” The patent provides a method of modifying a phosphomonoester moiety of a target compound by: a) providing a target compound having an electrophilic moiety and a phosphomonoester moiety; b) contacting the target compound with a first carbodiimide compound under conditions for preferential addition of the first carbodiimide compound to the electrophilic moiety over the phosphomonoester moiety, forming an electrophile-protected target compound; and c) contacting the electrophile-protected target compound with a second carbodiimide compound and a nucleophilic compound under conditions for addition of the nucleophilic compound to the phosphomonoester.

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Panomics, now Affymetrix, has received US Patent No. 7,803,541, “Multiplex branched-chain DNA assays.” The patent claims methods for detecting two or more nucleic acids in a multiplex branched-chain DNA assay. Different nucleic acids are captured through cooperative hybridization events on different, identifiable subsets of particles or at different selected positions on a spatially addressable solid support. Kits are also provided.

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Affymetrix has also received US Patent No. 7,803,609, “System, method, and product for generating patterned illumination.” A method for generating an interference pattern at a probe array is described. The method includes directing light at a first waveguide and second waveguide, where the first and second waveguides are positioned adjacent to each other and the output from the first and second waveguides produce an interference pattern; and directing the interference pattern at the probe array. According to the patent, the probe array has a biopolymer affixed to the surface of a support selected from the group consisting of nucleic acids, oligonucleotides, amino acids, proteins, peptides, hormones, oligosaccharides, lipids, glycolipids, lipopolysaccharides, phospholipids, inverted nucleotides, peptide nucleic acids, and meta-DNA. The detector can be a charge-coupled device; an electron-multiplying, charge-coupled device, a complementary metal-oxide semiconductor, active pixel sensor, or photomultiplier tube.

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The University of California of Oakland has received US Patent No. 7,803,542, “Signal-on architecture for electronic, oligonucleotide-based detectors.” The patent provides architecture for oligonucleotide-based detectors that lead to order-of-magnitude increases in signal gain and sensitivity compared to other detectors. The detectors rely on base pairing between two oligonucleotide strands, the sensor strand and the blocker strand. The formation of comparatively rigid, duplex DNA prevents the redox moiety from approaching the electrode surface, suppressing Faradaic currents, according to the patent. When a target is added to the system, the target displaces the blocker strand and binds to the sensor strand, liberating the end of the redox-labeled oligonucleotide to produce a flexible element. This, in turn, allows the redox moiety to collide with the electrode surface, producing a readily detectable Faradaic current.

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Chung Hua University of Hsinchu, Taiwan, has received US Patent No. 7,805,175, “Microarray bioprobe device integrated with a semiconductor amplifier module on a flexible substrate.” The patent provides a microarray integrated with a semiconductor amplifier module, which integrates microarray probes and thin film transistors on a substrate by micro-electro-mechanical system processes and semiconductor processes. According to the patent, a signal from the microarray is amplified through a near amplifier to increase signal-to-noise ratio and impendence matching.

This study demonstrated that the GoldenGate assay is a very efficient tool for high-throughput genotyping of polyploid wheat, opening new possibilities for the analysis of genetic variation in wheat and dissection of genetic basis of complex traits using association mapping approach. PMID: 19449174 [PubMed - as supplied by publisher] (Source: TAG. Theoretical and Applied Genetics)