Transcript ICSB3: DRPM Measures

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
RP11
The human genome project sequence 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
SLC24A5
OCA2
OCA2
DNA (biallelic bp in bold in central codon)
one RP11 allele
A111T atgttgcaggc Rca actttcatggcagcg
(R=g = darker skin)
R305W ccatcagcatc Ygg gcctccctgcagcag
(Y=c = bluer eyes)
R419Q accggctctcc cRg ggacgggtgtgggcc
(R=g = bluer eyes)
Underlined cg dinucleotides
(SLC24A5 15 q21.1; OCA2 15 q11.2-q12 )
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.
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.
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
rs11089130
position
14431347
0
C
1
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 1
NA06985 2
NA07022 1
NA07056 2
PGP: Identity
traits,
[low stigma
diseases]
(treatable)
Jon Will
DC
Down
Syndrome
21q22.3
dermatoglyphs
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)
Self reported
Environmental &
Phenotype data
Major Ancestry
Current marital status
Academic/professional degrees earned
Living arrangement (ie alone, with spouse)
Years worked in OR
Current weight
Nurses health Study (NHS)
Weight at age 18
How many times (past 10 years) have you donated blood?
Blood type / RH factor
• Personal and Physical
• Reproductive History
• Family History
• Environmental, Personal Exposure
• Diet and Supplement Use
• Physical Activity
• Screening History
• Disease Outcomes
• Medication Use
• Psychosocial
Weight change over last 2 years-- min-max
Methods of weight loss of 10+ lbs.
Waist measurement
Hip measurement
Upper arm measurement
How many natural teeth do you have?
In the last 2 years, have you had periodontal surgery?
When did knee pain begin?
How often do you have difficulty holding your urine
Number of moles on your left arm (>3mm)
Total hours of sleep per day (24hr)
Usual sleeping position
Do you snore?
Do you have difficulty with your balance?
# times you've fallen to the ground in the past year