Notes on personal genomics:
De novo mutations occur at <100 per generation: http://massgenomics.org/2012/08/de-novo-mutations-and-human-disease.html
The NA12878 genome from "Utah pedigree 1463" may be the genome that fhas been sequenced the most times. (http://blog.goldenhelix.com/?p=1725). It is a candidate for use as a reference genome with respect to sequencing quality. (http://nxseq.bitesizebio.com/articles/which-way-forward-in-ultra-high-throughput-genomic-sequencing-reference-materials-and-performance-measurements/)
- 1 Personal genomics topics
- 2 Compression and storage
- 3 Single Nucleotide Polymorphisms (SNPs)
- 4 Imputation
- 5 expressed quantitative trait loci (eQTL)
- 6 Genomics projects
- 6.1 100k foodborne pathogen genome project
- 6.2 Human Genome Diversity Project
- 6.3 Genome 10K Project
- 6.4 Cancer Genome Atlas
- 6.5 Human Microbiome Project
- 6.6 1000 Genomes Project
- 6.7 Personal Genome Project (PGP)
- 6.8 International HapMap Project
- 6.9 ENCODE
- 6.10 Colloborative Oncology Gene-Environment Study
- 6.11 Online Mendelian Inheritance in Man (OMIM)
- 7 Direct to Consumer (DTC) genotypcing services
- 8 Interpretation tools
- 9 Journals
- 10 Blogs and commentary
- 11 Software
- 12 Public genomes
- 13 DTC genomics companies
- 14 Ethical, Legal and Social Implications (ELSI)
- 15 Databases
- 16 Genome annotation and curation
- 17 Educational and instructional material
- 18 Research groups
- 19 Bibliography
- 20 Medical genomics and genomic medicine
- 21 Personal genomics
- 22 Metagenomics
- 23 Links
Personal genomics topics
Birth and maternal health
Ruth Landau, MD. Genetic Contributions to Labor Pain and Progress. Clinics in Perinatology Volume 40, Issue 3, September 2013, Pages 575–587.
Compression and storage
Efficient storage of high throughput sequencing data using reference-based compression http://genome.cshlp.org/content/early/2011/01/18/gr.114819.110
CRAM toolkit: http://www.ebi.ac.uk/ena/about/cram_toolkit
The Human Genome Contracts Again: http://bioinformatics.oxfordjournals.org/content/early/2013/06/22/bioinformatics.btt362.short?rss=1
Single Nucleotide Polymorphisms (SNPs)
SISRS: SNP Identification from Short Read Sequences: http://arxiv.org/abs/1305.3665
General Information about dbSNP, Single Nucleotide Polymorphisims, and Genetics: http://www.ncbi.nlm.nih.gov/books/NBK3856/
The number of SNPs in the human genome has been estimated to ~ 10 million (source?).
From SNPedia: "SNPedia is a wiki investigating human genetics. We share information about the effects of variations in DNA, citing peer-reviewed scientific publications. It is used by Promethease to analyze and help explain your DNA. "
The current state of dbSNP: http://massgenomics.org/2012/01/the-current-state-of-dbsnp.html
Human Gene Mutation Databasse:
Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/omim
- Polymorphism in LRRK2. Associated with Parkinson's disease.
- My genotype:GG (normal)
- Silent mutation in the oxytocin receptor (OXTR) gene.
- My genotype: AG (reference GG)
- My genotype: AA (reference: TT)
- SNP determining eye color?
- My genotype: GG (minor allele: G)
- My genotype: AA (normal)
- "Warrior vs Worrier"
- My genotype: GG ("warrior")
Genotype imputation for genome-wide association studies.: http://www.ncbi.nlm.nih.gov/pubmed/20517342
expressed quantitative trait loci (eQTL)
The NHGRI Genome Sequencing Program (GSP): http://www.genome.gov/10001691
100k foodborne pathogen genome project
Human Genome Diversity Project
Genome 10K Project
Aims to obtain genomic information for 10 000 vertebrate species.
Cancer Genome Atlas
Human Microbiome Project
1000 Genomes Project
The 1000 genomes project aims to sequence ~2500 samples at 4x to uncover most genetic variants having a frequency of at least 1 % in the populations studied.
Personal Genome Project (PGP)
"The Personal Genome Project aims to publish the genomes and medical records of 100 000 volunteers. As of March 2013, the number of enrolled participants is about 2500, of which there are available full-genome datasets for about 75. Some participants for which full genome datasets are not available, have uploaded data from genotyping services such as 23AndMe."
Unofficial wiki: http://wiki.personal-genome.org/index.php?title=Main_Page
International HapMap Project
Single Nucleotide Polymorphisms (SNPs) are often inherited together. The genotypes at some SNPs may thus be predicted by the genotype at one or more other SNPs. Groups of co-inherited SNPs are called "haplotypes". The HapMap project identifies common haplotypes and "tag" SNPs that uniquely identifies haplotypes.
From http://hapmap.ncbi.nlm.nih.gov/whatishapmap.html : "The number of tag SNPs that contain most of the information about the patterns of genetic variation is estimated to be about 300,000 to 600,000, which is far fewer than the 10 million common SNPs."
As part of the HapMap project, new SNPs sites were identified in order to serve as haplotype tags.
Colloborative Oncology Gene-Environment Study
Online Mendelian Inheritance in Man (OMIM)
Direct to Consumer (DTC) genotypcing services
Genome Biology: http://genomebiology.com/
Blogs and commentary
SNPedia blog: http://snpedia.blogspot.no/
UW Genome Sciences - Distinguished Faculty Interview Series: Joe Felsenstein : https://www.youtube.com/watch?v=3wO39cm0a2M
1000$ Genome / economy of sequencing
Genomic hyperbrowser: http://hyperbrowser.uio.no/hb/
Genome Workbench SNP Tools (GST) Quick Start: http://www.ncbi.nlm.nih.gov/books/NBK3859/
Variant annotation tools: http://varianttools.sourceforge.net/Annotation/DbSNP
A review of genomic data warehousing systems: http://bib.oxfordjournals.org/content/early/2013/05/14/bib.bbt031.short?rss=1&utm_source=buffer&utm_medium=twitter&utm_campaign=Buffer&utm_content=buffer656ea
MISO open-source LIMS: http://www.tgac.ac.uk/miso/
Complete Genomics 69 Genomes dataset: http://www.completegenomics.com/public-data/69-Genomes/
Genomes unzipped: http://www.genomesunzipped.org/data
Banana genome hub: http://banana-genome.cirad.fr/
Crowdsourcing the Corpasome: http://www.youtube.com/watch?v=sV7dD1DcQwQ&feature=youtu.be&a
DTC genomics companies
Ethical, Legal and Social Implications (ELSI)
See also: NCBIs interactions with Locus-Specific Data Bases (LSDB): http://www.ncbi.nlm.nih.gov/refseq/rsg/lsdb/
ALFRED The ALlele FREquency Database: http://alfred.med.yale.edu/
PheGenI - Phenotype Genotype Integrator: http://www.ncbi.nlm.nih.gov/gap/phegeni
The Human Gene Mutation Database (HGMD): http://www.hgmd.cf.ac.uk/ac/index.php
Information: General Information about dbSNP as a Database Resource: http://www.ncbi.nlm.nih.gov/books/NBK44469/
dbSNP fact sheet: ftp://ftp.ncbi.nih.gov/pub/factsheets/Factsheet_SNP.pdf
Finding Information in a dbSNP Data Report: http://www.ncbi.nlm.nih.gov/books/NBK44476/
SNP faq archive: http://www.ncbi.nlm.nih.gov/books/NBK3848/
NCBI Handbook chapter 5 - the dbSNP database: http://www.ncbi.nlm.nih.gov/books/NBK21088/
dbSNP data content information: http://www.ncbi.nlm.nih.gov/books/NBK3853/
Using dbSNP Data Reports: http://www.ncbi.nlm.nih.gov/books/NBK3854/
Clustered RefSNPs (rs) and Other Data Computed in House: http://www.ncbi.nlm.nih.gov/books/NBK44417/
SNP attributes: http://www.ncbi.nlm.nih.gov/projects/SNP/docs/rs_attributes.html
General dbSNP Search Options: http://www.ncbi.nlm.nih.gov/books/NBK44371/
Searching NCbI's dbSNP database: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078622/
SNP search: http://www.ncbi.nlm.nih.gov/snp?TabCmd=Limits
The database is updated periodically, resulting in a new build number. The current build number (april 2012) is 137. For every new build, refSNPs (rs#) are re-mapped and re-clustered on the latest genome assembly. SNP submissions (ss#) which have the same position in the genome are merged into one rs#. rs numbers which become redundant after merging are not reused. SNPs and indels are not merged, as these are distinct types of "mutational events" (http://www.ncbi.nlm.nih.gov/books/NBK21088/).
Note that from Homo Sapiens annotation release 104 and onwards, annotation releases are given separate numbers, distinct from genome build numbers.
rs and ss numbers:
All new submissions are given an ss number. After each mapping, all submissions which are mapped to the same site are clustered in one rs number. The submission (ss number) with the longest flanking sequence becomes the rs cluster exemplar. (http://www.ncbi.nlm.nih.gov/books/NBK44391/)
The alleles field:
The order of the alleles listed in the alleles field does NOT carry any biological meaning. Alleles are listed in alphabetical order. Note that some SNPs have different minor alleles between different populations. dbSNP maps SNPs to all major assemblies - the different assemblies sometimes have different alleles at a particular SNP position.
N and Y designations (www.ncbi.nlm.nih.gov/books/NBK44476/):
"N" is the designation for "tested, but results indeterminate".
"Y" is the designation for genotypes from males for SNPs that map to the X chromosomes
Sample size: There are two sample size numbers: The assay sample size is the number of chromosomes used to ascertain or discover the variation. The population sample size is the number of chromosomes used as the denominator when computing estimates of allele frequencies.
refSNP validation and quality:
"Double hit": refSNPs with both alleles seen at least twice.
Variation functional class (http://www.ncbi.nlm.nih.gov/books/NBK21088/#ch5.ch5_4_11_1): For each SNP, a functional context is determined by inspecting the flanking sequences, describing the function of the sequence the SNP is located in. Examples are "locus region", "coding synon", "coding non-synon", mRNA-UTR, intron.
If either allele in the variation is a non-synonymous change, then the variation is classified as non-synonymous; otherwise, the variation is classified as a synonymous variation
Global minor allele frequency (MAF):
The minor allele frequency for a given rs, reported with respect to a default global population (currently based on 1000 genomes project data). Given 3 alleles with frequencies of 0.50, 0.49, and 0.01, the MAF will be reported as 0.49. "MAF source": Data source for MAF calculation.
SNP name(s) according to Human Genome Variation Society nomenclature. See http://www.hgvs.org/mutnomen/recs.html#general. Note that "according to HGVS nomenclature, the allele before the ">" sign is simply the base located on the reference sequence at the position specified in the HGVS name — it does not have to be the major allele." (http://www.ncbi.nlm.nih.gov/books/NBK44476/)
The origin of variant alleles reported by the submitter(s). Possible values are germline, somatic or unknown.
Ancestral allele (http://www.ncbi.nlm.nih.gov/books/NBK84687/):
Ancestral allele version, as determined by comparison with Chimpanzee DNA.
Map to genome build: Version number of the genome assembly used for SNP mapping.
Integrated maps: Shows information on the SNP location and mapping in available genome assemblies. The contig alleles on different assemblies are often the same, but not always.
Genome annotation and curation
Concensus Coding Sequence (CCDS) project: http://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi
IGS annotation service: http://ae.igs.umaryland.edu/cgi/index.cgi
NCBI prokaryotic genome annotation pipeline: http://www.ncbi.nlm.nih.gov/genome/annotation_prok/
RATT Rapid Anotation Transfer Tool: http://ratt.sourceforge.net/
Review - The automatic annotation of bacterial genomes. http://bib.oxfordjournals.org/content/14/1/1.full
A semi-automated genome annotation comparison and integration scheme: http://www.biomedcentral.com/1471-2105/14/172/abstract
Educational and instructional material
Sequencing studies in human genetics: design and interpretation: http://www.nature.com/nrg/journal/vaop/ncurrent/full/nrg3455.html
SNPedia: a wiki supporting personal genome annotation, interpretation and analysis: nar.oxfordjournals.org/content/40/D1/D1308.long
dbSNP database: http://www.ncbi.nlm.nih.gov/projects/SNP/
Book - Exploring personal genomics: http://exploringpersonalgenomics.org/
UCSC Genome Browser: http://genome.ucsc.edu/
CEPH panel: http://hg.wustl.edu/hdk_lab_manual/14/14_1.html
Efficient storage of high throughput sequencing data using reference-based compression: http://genome.cshlp.org/content/early/2011/01/18/gr.114819.110
Medical genomics and genomic medicine
Notable accomplishments in genomic medicince: http://www.genome.gov/27551536
SSAGA, Symptom and Sign Assisted Genome Analysis:
Report on use of medical genetics in Norway (Norwegian): http://home.hio.no/~nilss/rapport.pdf
Microarrays and DNA Sequencing Improve Prenatal Testing: http://www.medscape.com/viewarticle/775687
Prenatal Whole Genome Sequencing: Just Because We Can, Should We? http://www.thehastingscenter.org
Noninvasive prenatal diagnosis empowered by high-throughput sequencing.: http://www.ncbi.nlm.nih.gov/pubmed/22467171
Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample: http://www.nejm.org/doi/full/10.1056/NEJMoa1208594
In the news:
Do-it-yourself genetic testing: http://genomebiology.com/2010/11/10/404
"integrated personal omics profiling" (iPOP): http://download.cell.com/chemistry-biology/pdf/PIIS1074552113001749.pdf?intermediate=true
SeqAnswers personal genomics forum: http://seqanswers.com/forums/forumdisplay.php?f=14
Metagenomic Approaches for Exploiting Uncultivated Bacteria as a Resource for Novel Biosynthetic Enzymology: http://download.cell.com/chemistry-biology/pdf/PIIS1074552113001683.pdf?intermediate=true
Untangling Genomes from Metagenomes: Revealing an Uncultured Class of Marine Euryarchaeota: http://www.sciencemag.org/content/335/6068/587