How many personal genomes are available today?

1. How many personal genomes are available today? 1. Venter 3X diploid = 1.5X haploid 2. Public HGP haploid ~7X 93% 1E-4 3. $1000 500K SNPs 3000 Mbp/.5M = 1/6000 >1% SNPs 33 M 3300 cM What is it? 6E9 bp accuracy: (1E-4 = 6E5 errors) 1E-9

2. RP11 The human genome projectsequence is largely from one man from Buffalo, NY (code RP11). Out of ten volunteers in 1997, one male was “selected at random … Unfortunately, the attempt to prepare EBV-transformed cells for the RPCI-11 donor failed. As a consequence of the double-blind donor selection procedure, it was impossible to obtain a second sample from the same male donor for a second attempt to establish transformed cells.” See (Osoegawa et al 2001). (~7X haploid coverage) Another donor identified himself in 2002. (3X diploid coverage, no cell line) Gene DNA (biallelic bp in bold in central codon) one RP11 allele SLC24A5 A111T atgttgcaggcRca actttcatggcagcg (R=g = darker skin) OCA2 R305W ccatcagcatc Ygg gcctccctgcagcag (Y=c = bluer eyes) OCA2 R419Q accggctctcc cRg ggacgggtgtgggcc (R=g = bluer eyes) Underlined cg dinucleotides (SLC24A5 15 q21.1; OCA2 15 q11.2-q12 )

3. HapMap: 270 individuals Note that the reference RP11 human genome represents only one of the two alleles (and is a composite, or missing in >300 regions). Both alleles are available for HapMap individuals from Ibadan, Nigeria (YRI), Tokyo, Japan (JPT), Beijing, China (CHB), Utah, USA (CEU). Stranger .. Dermitzakis (2007) Science 315:848-53. Relative impact of nucleotide and copy number variation on gene expression phenotypes. SNPs, CNVs captured 84%, 18% of the total detected genetic variation in 14,925 RNAs respectively. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299-1320. 2005.

4. HapMap: Success ARMD 50% of variance ARMD 1q32 Complement Factor H rs1061147 1277T-C exon 9 Li .. Abecasis (2006) CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.Nat Genet. 2006 Sep;38(9):1049-54. Maller .. Seddon. (2006) Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet.38:1055-9.

5. HapMap: Navigation http://www.hapmap.org/downloads/phasing/2006-07_phaseII/00README.txt http://www.hapmap.org/downloads/phasing/2006-07_phaseII/phased/ genotypes_chr21_CEU_r21_nr_fwd_legend.txt.gz 20-Jul-2006 13:35 256K genotypes_chr21_CEU_r21_nr_fwd_phased.gz 20-Jul-2006 13:35 754K genotypes_chr21_CEU_r21_nr_fwd_sample.txt.gz 20-Jul-2006 13:34 304 legend.txt rs ID position 0 1 rs11089130 14431347 C G rs915674 14433624 A G sample.txt : ordered list of individual ids that corresponds to the _phased file. For the CEU and YRI panels the individual id's are arranged as follows but the _phased files do not contain the haplotypes of the children as these can be inferred from the parents phased : one haplotype per row. For CEU and YRI: row 1 - trio 1 parent 1 transmitted haplotype row 2 - trio 1 parent 1 untransmitted haplotype row 3 - trio 1 parent 2 transmitted haplotype row 4 - trio 1 parent 2 untransmitted haplotype row 5 - trio 2 parent 1 transmitted haplotype … NA06993 1NA06985 2NA07022 1NA07056 2

6. Hair: Baldness [alopecia](minoxidil) Eyes: [Near/Far-sightedness](glasses) Iris color [ARMD] (glasses) Face: [Developmental syndromes, Wrinkles] (Botox) Brain: ADHD(Ritalin); Depression(Prozac); Headache(analgesics) Sleep & Circadian (caffeine, amphetamine, modafinil) Motion sickness (Dramamine, and Scopolamine) Lip: [Cleft palate] (surgery); [Hirsutism] (calcium thioglycolate) Ears: Sensitivity (hearing aids) Nose: Shape [breathing disorders] (CPAP) Mouth: Halitosis, throat exams; aerosols [airborne pathogens] Digestion [reflux, gas,ulcer] (antibiotics, antacids, PPIs) Skin: Perspiration, Body odor, Pheromones (deodorants) Surface texture [psoriasis] (topicals, photo-treatments) Immune components [acne] (topical antibiotics) Skin color [vitamin D & sunburn] (supplements, SPF cream) Hands: Dermatoglyphics [syndromes], [Arthritis](corticosteroids) Internal sensors: Proprioceptor, Repetitive stress (NSAIAs) Body: Height [Marfan] [short stature] (hGH) Weight [anorexia] [obesity] (Orlistat, Phentermine, Sibutramine) Allergies (antihistamines, cortisone, epinephrine, theophylline) Metabolic polymorphisms (vitamins, minerals, insulin) Back: Strain sensitivity [IDD] (analgesics) Feet: Plantar fasciitis (orthotic shoes) Athlete’s foot (miconazole, itraconazole, terbinafine, salicylate) PGP: Identity traits, [low stigma diseases] (treatable) Jon Will DC Down Syndrome 21q22.3 dermatoglyphs

7. Self reported Environmental & Phenotype data Nurses health Study (NHS) • Personal and Physical • Reproductive History • Family History • Environmental, Personal Exposure • Diet and Supplement Use• Physical Activity • Screening History • Disease Outcomes • Medication Use • Psychosocial