Revision as of 11:35, 9 June 2013

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 has 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/)

NA12878 datasets: https://docs.google.com/spreadsheet/ccc?key=0ArAo1qqJJDHQdHo0U1FzQV9JYVZhdnh2TGtlb1NQZXc#gid=0

Single Nucleotide Polymorphisms (SNPs)

http://www.isogg.org/wiki/Single-nucleotide_polymorphism

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/

Promethease: http://snpedia.com/index.php/Promethease

The number of SNPs in the human genome has been estimated to ~ 10 million (source?).

dbSNP:

http://www.ncbi.nlm.nih.gov/snp

http://www.ncbi.nlm.nih.gov/projects/SNP/

http://en.wikipedia.org/wiki/DbSNP

SNPedia:

http://www.snpedia.com/index.php/SNPedia

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

OpenSNP:

https://www.opensnp.org/

SNPnexus:

http://snp-nexus.org/

dbGaP:

http://www.ncbi.nlm.nih.gov/gap

GWAScentral:

Human Gene Mutation Databasse:

NextBio:

http://www.nextbio.com/b/nextbioCorp.nb

http://www.hgmd.cf.ac.uk/ac/index.php

https://www.gwascentral.org/

Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/omim

Interesting SNPs

rs34637584

Polymorphism in LRRK2. Associated with Parkinson's disease.
My genotype:GG (normal)

Rs53576

Silent mutation in the oxytocin receptor (OXTR) gene.
My genotype: AG (reference GG)

Rs9939609

My genotype: AA (reference: TT)

rs12913832

SNP determining eye color?
My genotype: GG (minor allele: G)

rs1799971:

My genotype: AA (normal)

Rs4680:

"Warrior vs Worrier"
My genotype: GG ("warrior")

Imputation

http://www.genomesunzipped.org/2013/03/learning-more-from-your-23andme-results-with-imputation.php#more-5390

http://www.ncbi.nlm.nih.gov/pubmed/20517342

expressed quantitative trait loci (eQTL)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650863/

Genomics projects

100k foodborne pathogen genome project

http://100kgenome.vetmed.ucdavis.edu/

Human Genome Diversity Project

http://en.wikipedia.org/wiki/Human_Genome_Diversity_Project

Genome 10K Project

Aims to obtain genomic information for 10 000 vertebrate species.

http://genome10k.soe.ucsc.edu/

Cancer Genome Atlas

https://tcga-data.nci.nih.gov/tcga/tcgaHome2.jsp

Human Microbiome Project

http://www.hmpdacc.org/

http://commonfund.nih.gov/hmp/

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001377

1000 Genomes Project

http://www.1000genomes.org

http://en.wikipedia.org/wiki/The_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.

An integrated map of genetic variation from 1,092 human genomes

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.

http://www.personalgenomes.org/

http://en.wikipedia.org/wiki/Personal_Genome_Project

International HapMap Project

http://hapmap.ncbi.nlm.nih.gov/

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.

A second generation human haplotype map of over 3.1 million SNPs

ENCODE

Colloborative Oncology Gene-Environment Study

http://www.cogseu.org/

Online Mendelian Inheritance in Man (OMIM)

http://www.omim.org/

Direct to Consumer (DTC) genotypcing services

23andme:

Interpretation tools

OpenSNP: http://opensnp.org/

Interpretome: http://esquilax.stanford.edu/

See http://www.ncbi.nlm.nih.gov/pubmed/22174289

http://nar.oxfordjournals.org/content/early/2013/04/29/nar.gkt342.full

Blogs and commentary

http://www.thegenesherpa.blogspot.no/

http://nextgenseek.com/

SNPedia blog: http://snpedia.blogspot.no/

http://www.genomesunzipped.org/

http://massgenomics.org

http://genomeref.blogspot.no/

http://thepersonalgenome.com/

http://omicsomics.blogspot.no/

http://core-genomics.blogspot.ca/

http://thegenomefactory.blogspot.no/

UW Genome Sciences - Distinguished Faculty Interview Series: Joe Felsenstein : https://www.youtube.com/watch?v=3wO39cm0a2M

http://manuelcorpas.com/

Software

http://www.openbioinformatics.org/annovar/

http://www.ncbi.nlm.nih.gov/tools/gbench/

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/

Galaxy: https://main.g2.bx.psu.edu/

http://www.enlis.com/research_edition.html

Public genomes

http://www.snpedia.com/index.php/Genomes

https://my.personalgenomes.org/users/

George Church

Craig Venter:

http://huref.jcvi.org/

http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0050254

James Watson: http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/

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

https://www.23andme.com/

Ethical, Legal and Social Implications (ELSI)

http://www.genome.gov/10001618

http://www.genomicslawreport.com/

http://www.pged.org/

http://www.technologyreview.com/featuredstory/513691/prenatal-dna-sequencing/

Genomic privacy:

http://www.nature.com/news/privacy-protections-the-genome-hacker-1.12940

Databases

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

http://www.rostlab.org/services/snpdbe/dosearch.php?id=mutation&val=rs12913832

dbSNP

http://en.wikipedia.org/wiki/DbSNP

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

Searching:

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

Updates:

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.

HGVS names:

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/)

Allele origin:

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.

FTP access:

ftp://ftp.ncbi.nlm.nih.gov/snp/00readme.txt

Citation: http://genome.cshlp.org/content/9/8/677.full

JSNP

http://snp.ims.u-tokyo.ac.jp/index.html

SNPedia

http://www.genome.gov/gwastudies/

Genome annotation and curation

Concensus Coding Sequence (CCDS) project: http://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi

Prokka: http://www.vicbioinformatics.com/software.prokka.shtml

BaSys: http://basys.ca/

RAST: http://rast.nmpdr.org/ ' http://www.jcvi.org/cms/index.php?id=141

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/

http://img.jgi.doe.gov/

http://derringer.genetics.utah.edu/cgi-bin/MWAS/maker.cgi

AgeS: http://bhsai.org/software/

http://www.gmod.org/wiki/WebApollo

RATT Rapid Anotation Transfer Tool: http://ratt.sourceforge.net/

Manatee: http://manatee.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

Bibliography

SNPedia: a wiki supporting personal genome annotation, interpretation and analysis: nar.oxfordjournals.org/content/40/D1/D1308.long

http://www.ncbi.nlm.nih.gov/pubmed/18154681?dopt=Abstract

Se also:

dbSNP database: http://www.ncbi.nlm.nih.gov/projects/SNP/

http://en.wikipedia.org/wiki/Full_Genome_Sequencing

http://en.wikipedia.org/wiki/Personal_genomics

http://nar.oxfordjournals.org/content/40/W1/W76.abstract

http://www.interpretome.com/

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

http://www.ncbi.nlm.nih.gov/pubmed/22274586

http://www.dnasnips.com/dnaSnips/Home.html

Medical genomics

http://www.perkinelmer.com/pdfs/downloads/CST_RGHS_SF_Dinwiddie.pdf

http://ww2.biol.sc.edu/~elygen/biol303/2012%20papers/Sequencing%20for%20diagnosis.pdf

http://www.childrensmercy.org/Health_Care_Professionals/Research/Pediatric_Genomic_Medicine/Software_Tools/

SSAGA, Symptom and Sign Assisted Genome Analysis:

Report on use of medical genetics in Norway (Norwegian): http://home.hio.no/~nilss/rapport.pdf

Companies:

Prenatal sequencing:

http://www.technologyreview.com/news/510181/a-brave-new-world-of-prenatal-dna-sequencing/

www.technologyreview.com/featuredstory/513691/prenatal-dna-sequencing/

http://www.genomeweb.com/sequencing/ready-prenatal-sequencing

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

/Publications/HCR/Detail.aspx?id=5909

Noninvasive prenatal diagnosis empowered by high-throughput sequencing.: http://www.ncbi.nlm.nih.gov/pubmed/22467171

http://blogs.discovermagazine.com/gnxp/2012/08/yes-we-should-prenatal-sequencing/#.UYOIFMq95rl

http://www.medicaldaily.com/articles/11466/20120813/genome-sequencing-genetic-testing-parents-children-ramifications.htm