Brooks-Wilson: "All interesting variants were present in unaffected individuals - some of whom may go on to develop disease" #AGBT14
11:23am February 13th 2014 via Hootsuite
Brooks-Wilson: But when 4/5 affected individuals: Found 24 likely candidates #AGBT14
11:20am February 13th 2014 via Hootsuite
Brooks-Wilson: Exomes in familial lymphoid cancer: Of 52 potentially damaging, rare variants in a family no single candidate emerges #AGBT14
I'm going to remember that one for a while. Memorable! RT @erlichya: I immensely enjoyed Nolan Kamitaki talk #AGBT14
11:09am February 13th 2014 via Hootsuite
RT @lexnederbragt: #agbt14 inspired blog post: "Defending 'no-tweeting/blogging' requests at conferences" http://t.co/RMeM4ZEbKW
11:08am February 13th 2014 via Hootsuite
Kamitaki: Q: Purer cell types? A: Second sample can change, but only a 10% variance. #AGBT14
10:33am February 13th 2014 via Hootsuite
Kamitaki: Q: Cell type samples? In culture? A: Found in urine (at lower freq). Could be epith. or low-level plasma DNA passed #AGBT14
10:32am February 13th 2014 via Hootsuite
Kamitaki: Q: What about Proteus, other syndromes? A: Will be adding more (less prevalent). Careful phenotyping done #AGBT14
10:31am February 13th 2014 via Hootsuite
Kamitaki: Q: Function of recurring mut sites? A: 3 of them are most common in cancer, other have looked at it #AGBT14
10:29am February 13th 2014 via Hootsuite
Kamitaki: Mutant alleles are usually present at frequencies of <10%. ddPCR ~2h $3/assay #AGBT14
10:28am February 13th 2014 via Hootsuite
Kamitaki: Early mutation could be lethal, later could be CLOVES, later still could be a single-limb syndrome. #AGBT14
10:27am February 13th 2014 via Hootsuite
Kamitaki: Looking at frequency of alleles, mode around 7% in the tissues tested. #AGBT14
10:26am February 13th 2014 via Hootsuite
PSA: If you are interested in digital PCR check out the QuantStudio 3D in the Camaxas 2 room (near the Marriott lobby) @LIFECorporation...
10:25am February 13th 2014 via Hootsuite
Kamitaki: Five PIK3CA muts were tested in the prior dataset. Could have looked at other gain-of-function. #AGBT14
10:24am February 13th 2014 via Hootsuite
Kamitaki: KTS - 22/27 (82%). LM - 18/20 (90%). FAVA 4/8 (50%). #AGBT14
10:23am February 13th 2014 via Hootsuite
Kamitaki: Ended up finding 26/30 CLOVE pts (87%) had PIK3CA mutations. #AGBT14
Kamitaki: Count of droplets, Poisson correction, looked at 30 CLOVES pts, and had seq data in-hand. Found 1/4 pts had PIK3A #AGBT14
10:22am February 13th 2014 via Hootsuite
Kamitaki: Selected digital PCR, allele-specific PCR. Illustrated method of different fluors, emulsions of ~15K droplets. #AGBT14
10:21am February 13th 2014 via Hootsuite
Kamitaki: Want a 'precise digital count of low-freq candidate alleles in affected tissue'. Frequency in biopsy tissues #AGBT14
10:20am February 13th 2014 via Hootsuite
Kamitaki: PIK3 pathway - cell growth, signalling PIK3CA are gain-of-function in many breast, colon tumors Helical and kinase domains #AGBT14
10:19am February 13th 2014 via Hootsuite
Kamitaki: Q: could disparate hypertrophy disorders be related by different points in development? What genes to focus on? #AGBT14
10:18am February 13th 2014 via Hootsuite
Kamitaki: Investigating somatic mosaicism. Could be in early dev, or a smaller scale. Clear cause cancer. All overgrowth disorders #AGBT14
10:17am February 13th 2014 via Hootsuite
Kamitaki: 4 disparate disorders illustrated: CLOVES, Klippel Trenaunay, Lymphatic malformation, FAVA. All present from birth #AGBT14
10:16am February 13th 2014 via Hootsuite
Up next: Nolan Kamitaki (Harvard): Four proliferative disorders arise overwheliming from somatic mutations in PIK3CA gene #AGBT14
10:15am February 13th 2014 via Hootsuite
Mohlke: A (con't): Could be a lot more variants involved in regulation #AGBT14
10:11am February 13th 2014 via Hootsuite
Mohlke: Q: (Chakravarti) is it one SNP or multiple sites? A: GALNT2 has at least of 4 var's, 1 has 80x xcr activity affect. #AGBT14
Mohlke: #IonTorrent 's own Mario Morken in the credits! (From NHGRI in a prior role.) #AGBT14
10:09am February 13th 2014 via Hootsuite
Mohlke:Uses a threshold of at least five reads per allele to det. whether allelic imbalance in effect for a particular loci. #AGBT14
10:08am February 13th 2014 via Hootsuite
Mohlke: Observes these imbalance effects in GALNT2, differential pull-down dep on variants, xcr activity also affected #AGBT14
10:06am February 13th 2014 via Hootsuite
Mohlke: Allelic imbalance in ChIP: allele diff's will affect peak height; in DNAse footprinting a different patter bet. alleles #AGBT14
10:04am February 13th 2014 via Hootsuite
Mohlke: Also for ChIP peak calling - cp BWA to GSNAP, a difference in peak calling at heterozygous sites. #AGBT14
10:02am February 13th 2014 via Hootsuite
Mohlke: Illustrates a C/A SNP plus another error illustrating need for allele-aware aligners. DNAse-Seq data compares BWA to GSNAP #AGBT14
Mohlke: Using higher throughput methods, laying out allelic imbalance measurements. But aligner mapping biases cause problems #AGBT14
10:00am February 13th 2014 via Hootsuite
Mohlke: Switching to HDL: GALNT2 gene, fine mapped 23 var's; cp to open chromatin, promoter and enh regions: many more var's ID'd #AGBT14
9:59am February 13th 2014 via Hootsuite
Mohlke: 2nd T2D example: CDC123/CAMK1D, similar footprinting to promoter region mutants in nuclear extracts. FOXA1/A2 pref. binding #AGBT14
9:57am February 13th 2014 via Hootsuite
Mohlke: Looking at two promoters P1 and P2 - P1 has a significant SNP risk variant, P2 doesn't. #AGBT14 Work in AJHG: http://t.co/Lfx2RPVOLp
9:55am February 13th 2014 via Hootsuite
Mohlke: In 2.7K Europeans, fine mapping the area, found strong signal. Overlapped with island open chromatin and promoter marks #AGBT14
9:52am February 13th 2014 via Hootsuite
Mohlke: T2D - looking at underlying variation in GWAS loci ID in 2010 Arap1 #AGBT14 2010 Nature Gen paper here: http://t.co/qRVriNMFLn
9:51am February 13th 2014 via Hootsuite
Mohlke: HDL-cholesterol GWAS manhattan plot: global lipid consort paper (Nat Gen 2013 paper here http://t.co/8lQD2GA79j) #AGBT14
9:49am February 13th 2014 via Hootsuite
Next up: Karen Mohlke (Univ NC) "Regulatory variants at GWAS loci for complex metabolic traits" #AGBT14
9:46am February 13th 2014 via Hootsuite
Chakravarti: Q: (E. Green): Other chromosomes / genes for enhancers? A: Second enh not highly conserved. Need approp. mouse lines #AGBT14
9:44am February 13th 2014 via Hootsuite
Chakravarti: Q: Genetics reminiscent of Autism (enteric morbidity)? A:ENS/CNS not looked at carefully in Autism (yet) #AGBT14
9:43am February 13th 2014 via Hootsuite
Chakravarti: Q (Gibbs): Are RET muts additive? A: Interaction of sets, enh. muts are brought into family by marriage; then penetrant #AGBT14
9:41am February 13th 2014 via Hootsuite
Chakravarti: (Ratios of prior list: 3% / 14% / 18% / 65% - isolated, whole variety of defects) #AGBT14
9:38am February 13th 2014 via Hootsuite
Chakravarti: Looking at 4 types of pts: single gene syndromic, large CNV syndromic, multiple abnormalities, isolated #AGBT14
9:36am February 13th 2014 via Hootsuite
Chakravarti: SOX10 impt xcr factor for gut development; can segment HSCR on the basis of genes that come into play #AGBT14
@KMeltzSteinberg What we might have expected from Eichler's talk: http://t.co/FUYBjbsz2U Recent paper: http://t.co/K97nQV7NLA #AGBT14
9:33am February 13th 2014 via Hootsuite
Chakravarti: Genesis and fate of neural crest cells contributing to the ENS: genes involved in earliest stages are involved w/ HSCR #AGBT14
9:32am February 13th 2014 via Hootsuite
Chakravarti: Newer less-confident data: high incidence of CNV in HSCR; chrom abnormalities, deletions: 42% unique pts have a CNV #AGBT14
9:28am February 13th 2014 via Hootsuite
Chakravarti: Looking for function - via ubiquination gene Ubr4 (E3 ligase), loss of fn in zebrafish gut develpment shown #AGBT14
9:27am February 13th 2014 via Hootsuite
