rs17602729 is the "most prevalent genetic disease mutation" in Caucasians according to PMID 11331279 as it appears to cause muscle pain after exercise for some people. Despite this relatively minor medical impact, it represents SNPedia’s ‘Nightmare before Christmas’.
As our understanding of the genome improves, the scientific community occasionally updates the reference standards. In August 23andMe updated from human reference genome build 36 to build 37.3. If you downloaded your raw data in July, this snp was at position 115037580 but after August it was at 115236057. SNPedia made similar changes back in 2010, but in 2012 we discovered that this snp hadn’t just changed position, it had also changed it's orientation. With this newest assembly, dbSNP flipped the SNP to the opposite strand of DNA, changing the normal G and variant A into normal C and variant T.
Confused? You’re not alone. ClinVar is the new NIH database of variation which affects human health. If you download their raw data and search for rs176027291 you will see that it shows all 4 alleles, with the G as normal. This is probably an artifact of the orientation change, but its likely that someone out there does have each allele. And each one of these nucleotide changes causes a different change to the amino. Since the most common variant is a premature stop codon, the altered aminos are probably viable with subtly different effects. Getting this SNP - and others that are similar challenges - straightened out in 2012 would take a Christmas miracle.
Monday, December 17, 2012
Sunday, December 16, 2012
O come all ye faithful
rs10937823 is one of the nicest gifts given to SNPedia this year. The minor rs10937823(T) allele has been associated with bipolar disorder in at least four independent studies as of last count, albeit with some inconsistency between populations as to which allele is the risk allele.
So why is it a gift? Because of who gave it to us. SNPedia exists and expands thanks in large part to the contributions of a community of people who feel it’s important to make scientific and medical findings about the genome accessible to all. Researchers, professors, physicians, techies, homemakers, students and many more contribute. Some are better at adding papers and p-scores, while others improve the grammar and spelling or rewrite to make the ideas accessible to a wider audience. Everyone contributes a little, and we’re all better off for it.
Our information about rs10937823 was primarily contributed by a med student in Stanford University’s Gene210 class. In this groundbreaking course from Professor Stuart Kim, students analyze their own genomes as they prepare to become doctors and researchers in a post-genome world.
Here’s a big Thank You! to our community – those who believe that if the genome matters, then getting the information out in ways that can be readily used matters too. Everytime a SNPedia page is edited an angel gets its wings.
So why is it a gift? Because of who gave it to us. SNPedia exists and expands thanks in large part to the contributions of a community of people who feel it’s important to make scientific and medical findings about the genome accessible to all. Researchers, professors, physicians, techies, homemakers, students and many more contribute. Some are better at adding papers and p-scores, while others improve the grammar and spelling or rewrite to make the ideas accessible to a wider audience. Everyone contributes a little, and we’re all better off for it.
Our information about rs10937823 was primarily contributed by a med student in Stanford University’s Gene210 class. In this groundbreaking course from Professor Stuart Kim, students analyze their own genomes as they prepare to become doctors and researchers in a post-genome world.
Here’s a big Thank You! to our community – those who believe that if the genome matters, then getting the information out in ways that can be readily used matters too. Everytime a SNPedia page is edited an angel gets its wings.
Saturday, December 15, 2012
(A;A) Christmas Platypus
rs55705857
is strongly associated with the most common form of primary brain
cancer, glioma, but it also achieves a distinction of being one of the most
strongly cancer-associated SNPs ever found in a SNP survey.
The study published in Nature Genetics this fall [PMID 22922872] by researchers at UCSF and the Mayo Clinic found that rs55705857(G) allele carriers are at 6 times higher risk for glioma formation than non-carriers, and in particular, for subtypes known to harbor IDH1 or IDH2 somatic mutations. It is comforting that while the mutation is common (between 2 - 8% of us harbor this allele), gliomas are rare (diagnosed in around 3 people per 100,000 every year) so most carriers will never develop such tumors. Unfortunately, for those that do, it’s often fatal, as it was for a good friend and colleague, Neil Ghiso.
The chromosomal region (8q24) this SNP is located in has previously yielded SNPs associated with ovarian and prostate cancer, but with much lower odds ratios. And while it’s clear the region is important in some regulatory manner, it’s not yet clear how. Perhaps another one of 2012’s top scientific stories – the first major release by the ENCODE project of data on functional elements in the genome – will help explain this.
And here’s where the platypus comes in. Even though it’s far from a coding region, sequencing shows that the common rs55705857(A) allele is invariant in all mammals, from humans through to, yes, the platypus. Here’s to the Christmas Platypus!
The study published in Nature Genetics this fall [PMID 22922872] by researchers at UCSF and the Mayo Clinic found that rs55705857(G) allele carriers are at 6 times higher risk for glioma formation than non-carriers, and in particular, for subtypes known to harbor IDH1 or IDH2 somatic mutations. It is comforting that while the mutation is common (between 2 - 8% of us harbor this allele), gliomas are rare (diagnosed in around 3 people per 100,000 every year) so most carriers will never develop such tumors. Unfortunately, for those that do, it’s often fatal, as it was for a good friend and colleague, Neil Ghiso.
The chromosomal region (8q24) this SNP is located in has previously yielded SNPs associated with ovarian and prostate cancer, but with much lower odds ratios. And while it’s clear the region is important in some regulatory manner, it’s not yet clear how. Perhaps another one of 2012’s top scientific stories – the first major release by the ENCODE project of data on functional elements in the genome – will help explain this.
And here’s where the platypus comes in. Even though it’s far from a coding region, sequencing shows that the common rs55705857(A) allele is invariant in all mammals, from humans through to, yes, the platypus. Here’s to the Christmas Platypus!
Friday, December 14, 2012
The 12 SNPs of Christmas 2012
It’s been another busy year for SNPedia. More and more folks not only use
SNPedia, but along with added features in Promethease, there’s more for every
person to learn about themselves. Our genomes become more interesting and
informative every year – DNA is the ultimate gift from our parents that keeps
on giving.
Like the Christmas carol, for each of the next 12 days we’ll
be singing about a SNP that caught our attention in 2012. In some ways this is
a Top 12 List, but it’s also a way for us to call attention and thank many of
you in our community. So here we go!
On the first day of Christmas … we’ve got to think of Santa
and his rs9939609 genotype. This SNP is in the FTO gene, and it
has long been associated with obesity, and in some populations, with Type-2
Diabetes. But just last month the Meyre Lab (McMaster Univ.) reported the
results of studying over 6,000 patients with depression in their Nature paper [PMID 23164817], and lo
and behold, rs9939609 is also associated
with resistance to depression. In fact, the minor A allele increases the
likelihood of both being obese AND being jolly. Perhaps Santa carries the A
allele?! We’ve been unable to get his DNA tested so far, but with the Ho Ho FTO theme in mind, will be leaving him a very special batch of cookies.
- The 12 SNPs of Christmas 2012
- (A;A) Christmas Platypus
- O come all ye faithful
- SNPedia’s Nightmare Before Christmas
- Hurðaskellir
- Christmas in the Heart
- Do you see what I MHC?
- Do you know what I know?
- I'm dreaming of a white (matter) Christmas
- Do they know it’s Christmas?
- Deck the halls with boughs of HOXB
- All I want for Christmas is a cure for HIV
Saturday, February 11, 2012
Denisova
In March 2010, scientists announced the discovery of a finger bone fragment of a juvenile female that lived about 41,000 years ago, found in Denisova Cave in Altai Krai, Russia. The full genome of this Denisova hominin was recently made available. The Unified genotyper was used to to add dbSNP 132 rs#s to the genome. The resulting VCF file can be read by Promethease to produce:
http://files.snpedia.com/reports/promethease_data/genome_DenisovaPinky_ui2.html
Through the 5519 SNPedia annotated snps we can learn more about this distant relative.
As first noted by John Hawks the snp rs7412 couldn't be reliably called, but rs429358 and rs4420638 were. These are consistent with an E4/E4.
rs3124314(C;C) suggest some curliness to the hair, while rs261360(A;G) is notable for heterozygosity. 5 other snps (rs12623288(A;A), rs1268789(G;G), rs1454292(T;T), rs6732426(T;T), rs908922(A;A)) are all consistent with straighter hair.
This should be female, but 23508 rs#s on the Y-chrom were found, with only rs9786465 being in SNPedia. The Unified Genotyper provides a partial explanation about the challenges of calling sex chromosomes.
The traits below are more about notoriously difficult to define and phenotype even in modern humans, and in a single sample of 40k year old non-human dna they should be covered in NaCl. However, deeper analysis needs to begin somewhere so ...
rs53576(G;G) in the Oxytocin receptor (OXTR). This genotype appears to be significantly better at accurately reading the emotions of others by observing their faces than were the remaining three-quarters of subjects, with (A;A) or (A;G). (G;G) individuals were also less likely to startle when blasted by a loud noise, or to become stressed at the prospect of such a noise.
Quite a few rare genos for intelligence with a possible emphasis on spatial working memory.
rs2710102 in CNTNAP2 has been associated with impaired speech development.
Denisova data lives in the eu-west-1b region of the Amazon cloud as snap-3cc2de54.
Processed with
GenomeAnalysisTK-1.4-25-g23e7f1b
dbsnp acquired from
ftp://gsapubftp-anonymous@ftp.broadinstitute.org/bundle/1.2/b37/dbsnp_132.b37.vcf.gz
Generated via
Log finishes with
It was run on an m1.large, but never managed to use both cpus, instead maxing out at 50% cpu usage.
Half of the /mnt/den is the chimpanzee data, so the alignment to human was 85gb for the T_hg19_1000g.bam + 9mb for the index.
Through the 5519 SNPedia annotated snps we can learn more about this distant relative.
APOE
As first noted by John Hawks the snp rs7412 couldn't be reliably called, but rs429358 and rs4420638 were. These are consistent with an E4/E4.
At present, the frequency of APOE*4 within all the major human groups remains higher in those populations…where an economy of foraging still exists, or food supply is now or has until recently been scarce, sporadically available or qualitatively poor. Under these environmental conditions, carrying the APOE*4 could be still useful.
--source PMID 10738542.
Hair Morphology
rs3124314(C;C) suggest some curliness to the hair, while rs261360(A;G) is notable for heterozygosity. 5 other snps (rs12623288(A;A), rs1268789(G;G), rs1454292(T;T), rs6732426(T;T), rs908922(A;A)) are all consistent with straighter hair.
Skin color
- rs1408799(C;C) in the Tyrosine Kinase Receptor is common only in caucasians, while rare in asians and africans. It increases risk of skin cancer.
- rs1540771(A;A) suggests the possibility of freckles
- rs1426654(G;G) darker skin
- rs642742(A;A) darker skin
- rs6058017(G;G) darker skin
Sex
This should be female, but 23508 rs#s on the Y-chrom were found, with only rs9786465 being in SNPedia. The Unified Genotyper provides a partial explanation about the challenges of calling sex chromosomes.
Caveat lector
The traits below are more about notoriously difficult to define and phenotype even in modern humans, and in a single sample of 40k year old non-human dna they should be covered in NaCl. However, deeper analysis needs to begin somewhere so ...
Optimism
rs53576(G;G) in the Oxytocin receptor (OXTR). This genotype appears to be significantly better at accurately reading the emotions of others by observing their faces than were the remaining three-quarters of subjects, with (A;A) or (A;G). (G;G) individuals were also less likely to startle when blasted by a loud noise, or to become stressed at the prospect of such a noise.
Intelligence
Quite a few rare genos for intelligence with a possible emphasis on spatial working memory.
- rs12639834(T;T)
- rs2295639(G;G)
- rs12143943(A;A)
- rs10498514(C;C)
- rs17586674(G;G)
- rs10879517(G;G)
- rs1265879(G;G)
- rs9300212(C;C)
- but rs1018381(T;T) doesn’t appear to have been helping any
Speech
rs2710102 in CNTNAP2 has been associated with impaired speech development.
Methods
Denisova data lives in the eu-west-1b region of the Amazon cloud as snap-3cc2de54.
Processed with
GenomeAnalysisTK-1.4-25-g23e7f1b
dbsnp acquired from
ftp://gsapubftp-anonymous@ftp.broadinstitute.org/bundle/1.2/b37/dbsnp_132.b37.vcf.gz
Generated via
java -jar GenomeAnalysisTK.jar -R /mnt/mydata/human_g1k_v37.fasta -T UnifiedGenotyper -I /mnt/den/denisova_genome/T_hg19_1000g.bam --dbsnp /mnt/mydata/dbsnp_132.b37.vcf -o /mnt/mydata/snps.raw.vcf > /mnt/mydata/alog.txtLog finishes with
INFO 10:11:25,697 UnifiedGenotyper - Visited bases 3101804739
INFO 10:11:25,697 UnifiedGenotyper - Callable bases 2862033547
INFO 10:11:25,698 UnifiedGenotyper - Confidently called bases 112644898
INFO 10:11:25,698 UnifiedGenotyper - % callable bases of all loci 92.270
INFO 10:11:25,698 UnifiedGenotyper - % confidently called bases of all loci 3.632
INFO 10:11:25,698 UnifiedGenotyper - % confidently called bases of callable loci 3.936
INFO 10:11:25,699 UnifiedGenotyper - Actual calls made 4989617
INFO 10:11:25,714 TraversalEngine - Total runtime 66799.27 secs, 1113.32 min, 18.56 hours
INFO 10:11:25,823 TraversalEngine - 0 reads were filtered out during traversal out of 1424486071 total (0.00%)It was run on an m1.large, but never managed to use both cpus, instead maxing out at 50% cpu usage.
[ec2-user@ip-10-234-51-252 den]$ df -H
Filesystem Size Used Avail Use% Mounted on
/dev/xvda1 8.5G 2.0G 6.5G 24% /
tmpfs 4.0G 0 4.0G 0% /dev/shm
/dev/xvdf 212G 170G 31G 85% /mnt/den
/dev/xvdg 159G 5.8G 145G 4% /mnt/mydata
[ec2-user@ip-10-234-51-252 mydata]$ ls -tral
total 5416212
drwxr-xr-x 4 root root 4096 Feb 9 15:03 ..
drwx------ 2 root root 16384 Feb 9 15:06 lost+found
-rw-rw-r-- 1 ec2-user ec2-user 4578627636 Feb 9 15:35 dbsnp_132.b37.vcf
-rw-rw-r-- 1 ec2-user ec2-user 12379076 Feb 9 15:35 dbsnp_132.b37.vcf.idx
-rw-rw-r-- 1 ec2-user ec2-user 942611555 Feb 10 10:11 snps.raw.vcf
-rw-rw-r-- 1 ec2-user ec2-user 12394492 Feb 10 10:13 snps.raw.vcf.idx
-rw-rw-r-- 1 ec2-user ec2-user 142784 Feb 10 10:13 alog.txt
drwxrwxrwx 3 root root 4096 Feb 10 12:16 .
Half of the /mnt/den is the chimpanzee data, so the alignment to human was 85gb for the T_hg19_1000g.bam + 9mb for the index.
Saturday, January 21, 2012
Promethease 0.1.126 UI2
Promethease version 0.1.126 is downloadable. The most recent improvements have been to UI2, which is only available in the $2 paid runs. The improvements make it easier to sort, filter and explore your genome. You can try them out by clicking on this Lilly Mendel UI2 report or just watch them in the video below.
Notable features
That last feature is intended to encourage more edits to SNPedia. We welcome your edits big or small.
The reports may be too large to view on iPads, and there are still some problems with the graph under IE, but more improvements will certainly follow. Your bug reports and feature requests to info@promethease.com can help it to grow in the right direction.
Give it a try! Lilly Mendel UI2
Notable features
- Sort by Magnitude, Frequency or # of References
- Green/red highlighting of good/bad news
- Turn on/off good, bad, not set, SNPs or genosets
- Filter out genos based on the Magnitude, # of References or both using AND/OR logic
- Type a question mark ? to bring up a help menu
- Ball & Spring graph is now in its own window, and can be zoomed with the mouse wheel
- A chooser for Medicines, Medical conditions and Topics, with progressive text search
- Each geno has a footer showing what categogies it belongs to, and allowing to to select all genos belonging to that category
- At the bottom of the page press '2x more' or just type the number of records you want
- Editor mode to link directly to the edit pages
That last feature is intended to encourage more edits to SNPedia. We welcome your edits big or small.
The reports may be too large to view on iPads, and there are still some problems with the graph under IE, but more improvements will certainly follow. Your bug reports and feature requests to info@promethease.com can help it to grow in the right direction.
Give it a try! Lilly Mendel UI2
Friday, December 9, 2011
The SNPedia Paper
SNPedia: a wiki supporting personal genome annotation, interpretation and analysis
Michael Cariaso; Greg Lennon
Nucleic Acids Research 2011; doi: 10.1093/nar/gkr798
Michael Cariaso; Greg Lennon
Nucleic Acids Research 2011; doi: 10.1093/nar/gkr798
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