BioTechniques – A Birthday Party for the Human Genome:
“…Decoding the human genome was a mile-stone in the history of science, not only for the sequence it gave us, but also for the inspiration it provided…”
“…In other words, the FDA has stated on the record that if a company offers to sell you your genome sequence without interpretation, they can do so without FDA intervention. And if you then wish to take that genome sequence and run it through any of the growing list of open-access tools for interpretation (such as Promethease), you’re free to do so…”
Lee Hood Promotes P4 medicine at AACC| GenomeWeb:
“Hood envisions that in the next 10 years, physicians will adopt a ‘systems approach to disease,’ whole-genome sequencing will be performed in the familial context, and patient-specific assays will be used biannually and will interrogate 2,500 proteins in order to quantify ‘wellness.’”
Exploring the Genetic Basis of Variation in Gene Predictions with a Synthetic Association Study: ”
Identifying DNA polymorphisms that affect molecular processes like transcription, splicing, or translation typically requires genotyping and experimentally characterizing tissue from large numbers of individuals, which remains expensive and time consuming. Here we introduce an alternative strategy: a ‘synthetic association study’ in which we computationally predict molecular phenotypes on artificial genomes containing randomly sampled combinations of polymorphic alleles, and perform a classical association study to identify genotypes underlying variation in these computationally predicted annotations. We applied this method to characterize the effects on gene structure of 32,792 single-nucleotide polymorphisms between two strains of the antibiotic producing fungus Penicilium chrysogenum. Although these SNPs represent only 0.1 percent of the nucleotides in the genome, they collectively altered 1.8 percent of predicted gene models between these strains. To determine which SNPs or combinations of SNPs were responsible for this variation, we predicted protein-coding genes in 500 intermediate genomes, each identical except for randomly chosen alleles at each SNP position. Of 30,468 gene models in the genome, 557 varied across these 500 genomes. 226 of these polymorphic gene models (40%) were perfectly correlated with individual SNPs, all of which were within or immediately proximal to the affected gene. The genetic architectures of the other 321 were more complex, with several examples of SNP epistasis that would have been difficult to predict a priori. We expect that many of the SNPs that affect computational gene structure reflect a biologically unrealistic sensitivity of the gene prediction algorithm to sequence changes, and we propose that genome annotation algorithms could be improved by minimizing their sensitivity to natural polymorphisms. However, many of the SNPs we identified are likely to affect transcript structure in vivo, and the synthetic association study approach can be easily generalized to any computed genome annotation to uncover relationships between genotype and important molecular phenotypes.
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(Via PLoS ONE.)
Type 1 diabetes (T1D) is an autoimmune disease resulting from the complex interaction between multiple susceptibility genes, environmental factors and the immune system. Over 40 T1D susceptibility regions have been suggested by recent genome-wide association studies; however, the specific genes and their role in the disease remain elusive. The objective of this study is to identify the susceptibility gene(s) in the 12q13 region and investigate the functional link to the disease pathogenesis. A total of 19 SNPs in the 12q13 region were analyzed by the TaqMan assay for 1,434 T1D patients and 1,865 controls. Thirteen of the SNPs are associated with T1D (best p = 4×10−11), thus providing confirmatory evidence for at least one susceptibility gene in this region. To identify candidate genes, expression of six genes in the region was analyzed by real-time RT-PCR for PBMCs from 192 T1D patients and 192 controls. SNP genotypes in the 12q13 region are the main factors that determine ERBB3 mRNA levels in PBMCs. The protective genotypes for T1D are associated with higher ERBB3 mRNA level (p<10−10). Furthermore, ERBB3 protein is expressed on the surface of CD11c+ cells (dendritic cells and monocytes) in peripheral blood after stimulation with LPS, polyI:C or CpG. Subjects with protective genotypes have significantly higher percentages of ERBB3+ monocytes and dendritic cells (p = 1.1×10−9); and the percentages of ERBB3+ cells positively correlate with the ability of APC to stimulate T cell proliferation (R2 = 0.90, p<0.0001). Our results indicate that ERBB3 plays a critical role in determining APC function and potentially T1D pathogenesis.
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Stratford JK, Bentrem DJ, Anderson JM, Fan C, Volmar KA, et al. (2010) A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma. PLoS Med 7(7): e1000307. doi:10.1371/journal.pmed.1000307 Read more…
Genetic Differences between Five European Populations.
Genetic Differences between Five European Populations.
Hum Hered. 2010 Jul 8;70(2):141-149
Moskvina V, Smith M, Ivanov D, Blackwood D, Stclair D, Hultman C, Toncheva D, Gill M, Corvin A, O’Dushlaine C, Morris DW, Wray NR, Sullivan P, Pato C, Pato MT, Sklar P, Purcell S, Holmans P, O’Donovan MC, Owen MJ, Kirov G
Aims: We sought to examine the magnitude of the differences in SNP allele frequencies between five European populations (Scotland, Ireland, Sweden, Bulgaria and Portugal) and to identify the loci with the greatest differences. Methods: We performed a population-based genome-wide association analysis with Affymetrix 6.0 and 5.0 arrays. We used a 4 degrees of freedom chi(2) test to determine the magnitude of stratification for each SNP. We then examined the genes within the most stratified regions, using a highly conservative cutoff of p < 10(-45). Results: We found 40,593 SNPs which are genome-wide significantly (p </= 10(-8)) stratified between these populations. The largest differences clustered in gene ontology categories for immunity and pigmentation. Some of the top loci span genes that have already been reported as highly stratified: genes for hair color and pigmentation (HERC2, EXOC2, IRF4), the LCT gene, genes involved in NAD metabolism, and in immunity (HLA and the Toll-like receptor genes TLR10, TLR1, TLR6). However, several genes have not previously been reported as stratified within European populations, indicating that they might also have provided selective advantages: several zinc finger genes, two genes involved in glutathione synthesis or function, and most intriguingly, FOXP2, implicated in speech development. Conclusion: Our analysis demonstrates that many SNPs show genome-wide significant differences within European populations and the magnitude of the differences correlate with the geographical distance. At least some of these differences are due to the selective advantage of polymorphisms within these loci.
PMID: 20616560 [PubMed - as supplied by publisher]
Roche, IBM Co-Developing Nanopore-based DNA Sequencing..
…Ultimately, the technology could improve throughput and reduce costs to where the whole human genome can be sequenced at a cost of between $100 and $1,000, Roche and IBM said..
10 interviews from WEF’s mHealth Summit. An interview with Paul Jacobs, Chairman and Chief Executive Officer, Qualcomm, USA at the mHealth summit of the World Economic Forum’s Global Agenda Council on the Future of Mobile Communications.
As part of an effort to provide its current customers with the latest rare variation content for genome-wide association studies, Illumina will roll out a supplementary BeadChip for its HumanOmni2.5-Quad DNA Analysis BeadChip alongside the launch of its HumanOmni5 BeadChip later this year [Read More]
