1 Mammals 2.0. Humanized mammals A 10 Mb-sized region of.. human chromosome 22 to be stably...
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Transcript of 1 Mammals 2.0. Humanized mammals A 10 Mb-sized region of.. human chromosome 22 to be stably...
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Mammals 2.0
Humanized mammals •A 10 Mb-sized region of .. human chromosome 22 to be stably maintained in mouse embryonic stem (ES) cells, and in mice. .. functional expression of human genes from the HAC in mice. (Human immune functions) [Note: 300 of these = 1 genome] (Nature Biotech 2000 “Manipulation of human minichromosomes to carry greater than megabase-sized chromosome inserts”)
•Human liver enzymes for drug toxicity testing CYP2 D6, C9, C19, etc.
•Human / mouse neural chimeras: (Stem Cells. 2007 “Brain transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model”)
•Next step “personalized mammals” For transplants and drug testing
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Intra-species variation in muscle mass
Myostatin nulls show enhanced muscle growth, decreased body fat & atherosclerosis (11-Jun-2009 Endocrine Society, Bhasin, BU)
Flex Wheeler
Prevalence of chronic conditions as a function of age for the US population 2003
http://www.senescence.info/definitions.html
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Ageing (891 species) Homo sapiens
Heterocephalus glaber
Cebus capucinus
Balaena mysticetus
Jeanne Calment of France (1875–1997)
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Engineering aging Naked Mole ratHeterocephalus
glaber 25 yearsEusocial
(Queen & Workers)Congenital insensitivity to
pain (CIPA)
MouseMus
musculus2.5 years
Candidate gene examples: Trp53, Polg, Hr, Bmi1, Clk1, Sirt1, Ucp2, Hr,
Ercc2, Atm, Foxo1
genomics.senescence.info
Quantitative Trait Distributions
Starr &Taggart. 2003. The Unity and Diversity of Life. 10th Ed. P. 189
acsweb.fmarion.edu/Pryor/bellcurve.htm
Polygenic: A & B .. heterogeneous: A or
B ..
0.00
0.01
0.02
0.03
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0.10
0 10 20 30 40 50
Normal (m=20, s=4.47)
Poisson (m=20)
Binomial (N=2020, p=.01)
Binomial, Poisson, Normal
Expectation E (rth moment) of random variables X for any distribution f(X)
First moment= Mean variance 2 and standard deviation
E(Xr) = Xr f(X) E(X) 2E[(X-2]
Pearson correlation coefficient C= cov(X,Y) = X-X )Y-Y)]/(X Y)
Independent X,Y implies C perfect anti-correlation =-1.0but C0 does not imply independent X,Y. (e.g. Y=X2)
P = TDIST(C*sqrt((N-2)/(1-C2)) with dof= N-2 and two tails.
where N is the sample size.
Mean, variance, & linear correlation coefficient
www.stat.unipg.it/IASC/Misc-stat-soft.html
p and q p q q = 1 – p two types of object or event.
Factorials 0! = 1 n! = n(n-1)!
Combinatorics (C= # subsets of size X are possible from a set of total size of n)
n!
X!(n-X)! C(n,X)
B(X) = C(n, X) pX qn-X np 2npq
(p+q)n = B(X) = 1
Binomial frequency distribution as a function of X {int n}
B(X: 350, n: 700, p: 0.1) = 1.53148×10-157 =PDF[ BinomialDistribution[700, 0.1], 350] Mathematica ~= 0.00 =BINOMDIST(350,700,0.1,0) Excel
P(X) = P(X-1) X = x e-X! 2
n large & p small P(X) B(X) np
For example, estimating the expected number of positives
in a given sized library of cDNAs, genomic clones,
combinatorial chemistry, etc. X= # of hits.
Zero hit term = e-
Poisson frequency distribution as a function of X {int }
Z= (X-
Normalized (standardized) variables
N(X) = exp(-2/2) / (2)1/2
probability density function
npq large N(X) B(X)
Normal frequency distribution as a function of X {-}