Progress in Genomics in the last few Years

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  10-18-08
• Progress in Genomics in the last few Years
  Future Prospects
• Genomics The study of genes and their functions.
  
• Includes
• understanding the structure of the genomes
• mapping genes and sequencing the DNA.
• Genomics examines the complex feedback mechanisms
  by which gene expression is controlled, and the
  interplay of genetic and environmental factors in
  disease.

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Genomics subspecialties include Functional
genomics - Describes the way in which genes and
their products, proteins, interact together in
complex networks in living cells. If these
interactions are abnormal, diseases can
result. Structural genomics - the dissection of
the architectural features of genes and
chromosomes. Comparative genomics - the
evolutionary relationships between the genes and
proteins of different species. Epigenomics
(epigenetics) - genetic effects not caused by
changing DNA sequences (usually involving
methylation) Pharmacogenomics - finding new
biological targets and new ways to design drugs
and vaccines.
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Types of Mutations Point Mutations - One base
added, deleted, or substituted for another
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Other Types of Mutations Groups of bases, or
whole genes may be added, deleted, inverted, or
copied or moved to new locations
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Other Types of Genetic Variation More Recently
Discovered In Humans Methylation - attachment of
CH3 groups to DNA, which affects gene expression,
and can be heritable. Identical twins may differ
here Copy Number Variation (CNV) - People can
have different numbers of copies of the same
gene. The same person can have different
numbers of copies in different tissues, or even
different on the members of a pair of the same
chromosomes. Thus there is more genetic
variation among humans than recently thought. At
a Webinar presentation this summer on CNV, the
estimate of the average genetic difference
between two random humans was upped from .1 to
.5
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Most mutations lower survival probability, so
they and their bearers were eliminated, at least
until modern society. Harmless ones may spread
within populations. This is called genetic drift.
Rarely, mutations enhance their carriers
survival chances within their environment, and
become the norm in that group. The latter two
types of mutations have produced the existing
races and sub-races from groups isolated in
different environs. Geneticists have been able to
analyse these mutations in recent years to trace
their migrations out of Africa and beyond in
surprising detail.
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Where and when groups of Homo sapiens migrated
from Africa,evolving as they went.
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Many religious fundamentalists deny evolution
happened at all. The dysgenic leftist religion
dogmatizes that evolution stopped acting on Homo
sapiens when some of them left Africa about
50,000 years ago. In reality, evolution has
continued to accelerate exponentially.
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Some Discoveries So Far About Recent Human
Evolution The FOXP2 gene, related to language
ability, changed to its present form about
200,000 years ago, Before modern humans left
Africa. About 37,000 years ago, a variant of a
gene called microcephalin arose among people who
had left Africa. This form of the gene causes
the brain to grow larger. It spread rapidly
among those who had left Africa, but is still
much less common in sub-Saharan Africans. This
change was soon followed by the flowering of the
Aurignacian culture in Europe, best known for
major improvements in the refinement of stone
and bone tools, and the impressively
sophisticated cave paintings in Spain and
southern France.
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A new allele of the gene ASPM arose 6,000 years
ago. This may have helped helped enable
development of writing and alphabets. It is
now carried by 44 of Caucasians, is less common
in East Asians, and rare to nonexistent in
sub-Saharan Africans. The work of the
Chinese-American geneticist Bruce Lahn, who
discovered these last two variants has,
tragically, apparently been stifled by
dysgenicists. There are surely more such
mutations left to be discovered. Since leaving
Africa, people have become genetically less
inclined to interpersonal violence and
aggression. This was necessary for, and
selected for, by the development of large
permanent settlements, which were a prerequisite
for civilization.
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The Most Biologically Successful
Human The typical male living in 1200 AD has 20
males today carrying his Y chromosome, because
there are 20 times as many people
now. Researchers have found one specific
Y-chromosome carried by about 16 million men,
mostly in Asia. They have determined it began
proliferating about 1200 AD., and is almost
surely that of Ghengis Khan. Ghengis had the
most attractive women of each conquered area
brought to him. He spent much of his time
breeding when not conquering. His numerous sons
generally did likewise.


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A Striking Example of Very Recent Human
Evolution From about 800 - 1800 AD, the Jews of
Europe, or Ashkenazim, were often restricted to
jobs in finance, requiring high abstract
intelligence. High quantitative reasoning
ability was intensely selected for This likely
selected for alleles which alter phospho-lipid
and sphingo-lipid metabolism in the brain,
because these can increase the number and
strength of synaptic connections in heterozygous
individuals. This led to a striking and
persistent 12 -15 point higher average IQ
Because of the nature of the IQ Bell Curve, the
proportion of Jews rises exponentially at the
higher end of the curve, where those are who
produce the most critical advances in math
science, the basis for modern civilization.
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Ashkenazim have won gt 23 of Nobel prizes in
science and medicine, tho only 0.2 of the
worlds population, despite discrimination,
persecution, and despite that being homozygous
for some of the related genetic changes produces
fatal neurological disorders, such as Tay-Sachs
disease.
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The Personal Genome
Project The largest current coordinated project
to get useful medical info from human genomics is
run by Prof. George Church, head of
computational genomics at Harvard Medical
School The Goal is to sequence the exome (the 1
of the genome that actually codes for proteins)
of 100,000 people. Volunteer participants agree
to anonymous online publication of both their
exome and much data on their phenome (the sum of
an individuals observable or measurable
attributes, such as height, weight, medical
history, et al.) All Researchers are free to
try to find statistical correlations between the
exome and phenomic traits.


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Trends in Cost of
Genomic Sequencing The current
price/performance leader is probably the
sequencer Churchs team developed. He says it
is running at 1/3 the cost of the Applied
Biosystems machine, which recently claimed to
have sequenced a human genome for 60,000 The
rate of improvement in cost/genome is making
Moores Law for cpus look like molasses flow in
January. Several groups are racing for the 10
million Archon X Prize for Genomics, which is
offered for the first team that can sequence 100
complete genomes in 10 days for lt 10,000 each.
A consensus of experts in the field think the
cost / genome can be brought down to about 1,000
within 10 years, making it a routine part of
preventive and diagnostic medical care for most
people.
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A startup called Pacific Biosciences vows to
sequence a genome in 15 minutes for less than
1,000 by 2013,bringing genomics to the masses.
They are backed by blue-chip venture capital
firms including Mohr Davidow and Kleiner
Perkins, Competitors Illumina (ILMN), Applied
Biosystems (ABI), and Helicos BioSciences (HLCS)
have gone public. Complete Genomics and VisiGen
Biotechnologies are still private. Analysts
say this market could jump from its current 1.5
billion in revenues to tens of billions.
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Some Personal Testing Analysis Available as of
Summer 2008 National Geographic Project 99.95.
Detects which branches of the Human diaspora your
genes come from. DeCode 23andMe 1,000.
Microarray tests for 1 million known variants.
Access to online database on medical risks
ancestry. Navigenics 2,500. Microarray tests
for 1 million known variants. Includes personal
counseling on medical risks. DNA Direct 175 -
3,456. Various tests related to specific medical
conditions. Knome Full genome sequence.
350,000 (price expected to drop soon)
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Potential Benefits
of Genomics - Personalized preventive medicine
and treatment based on individual risk profiles
and prediction of likely drug effects. Example
The Hi-blood pressure drug Bildil was almost
abandoned because it seemed not to help most
people. Jay Cohn noticed it helps most people of
African origin It probably enhances a protein, at
a low level in Africans, that rids the body of
excess salt. In the tropics, it is important to
retain salt, but in America the same genetically
lo level of that protein leads to chronic hi
blood pressure and strokes, which are more
prevalent among African Americans.
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More Benefits - A
vastly better understanding of human minds and
their emotional defects in coping with the modern
world. - A chance to reverse the current
mass-psychotic dysgenics policies and trends in
the West, currently retarding the advance of
civilization. These started as a paranoid
reaction to Germany and Japans errant eugenics
policies. There wont need to be any more racial
conflict, because everyone can potentially share
the best and most desirable genes
available. These improvements will be resisted
strongly, but will prevail because of the nearly
universal human instinct to improve prospects for
themselves and their children. It may be
possible to genetically engineer organisms to
economically produce renewable fuels and other
chemicals, including drugs.
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• Risks
• Congress recently passed a law intended to
  prevent discrimination
• based on genetic data.
• From history, we can predict that most of the
  inevitable deluge of
• related government antics will be late, based on
  ignorance, fear of
• change, and biased to favor the richest and most
  fanatic lobbies
• involved.
• - Stifling bureaucracy, and Long and costly law
  suits.
• - As usual, the rich and powerful will get first
  access to expensive
• new treatments and enhancements.
• - Terrorists and governments will be more easily
  able to engineer
• deadly vectors of pandemics. Al Qaida has said
  it is Muslims duty
• to get such weapons and use them against
  non-muslims.

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The American College of Medical Genetics
www.acmg.net is the main group trying to
establish standards of accuracy, honesty, and
public awareness of ethical implications. It is
open to all genetics-related professionals. Genet
ics in Medicine, now published monthly, is the
official journal of the ACMG. http//www.acmg.ne
t//AM/Template.cfm?SectionHome3
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• Summary
  (1 of 2)
• Studies of ancient and modern DNA have given
  vastly more
• accurate details on the evolutionary
  relationships of most major
• known species
• We now know to where and when, within a few
  thousand years, our
• ancestors went after the one main group of
  500-2,000 left Africa
• about 50,000 years ago
• We have only about 20-25 thousand genes, but
  their interrelated
• control mechanisms are much more complex than
  imagined until
• the last 5 years
• Price /performance of genetic sequencing is
  improving much
• faster than Moores Law. A full sequencing is
  likely to drop
• to 1,000 within 5-10 yrs.

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• Summary (2 of 2)
• Within a few years of we may be able to change
  our genomes
• phenomes with major effects
• These changes can bring huge benefits to
  individuals and society,
• but also hold great risks.
• The most imaginative researchers are well aware
  of
• our ignorance of how all the aspects of
  genetics and
• the environment interact.
• Craig Venter pithily summed it up after he
  finished
• sequencing his genome
• "We don't know sht about biology!".

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Sources Molecular
Biology of the Cell, 5th Ed., 2008 By Bruce
Alberts, Alexander Johnson, Julian Lewis, Martin
Raff, Keith Roberts, Peter Walter (the leading
cell biology textbook for gt 25 years) Before
the Dawn Recovering the Lost History of Our
Ancestors by Nicolas Wade, 2007, The Penguin
Press. 1 ET, Kodama G, Baldi P, Moyzis RK.
2006. Global landscape of recent inferred
Darwinian selection for Homo sapiens Proc Nat
Acad Sci USA 103135-140. 2 History of Ashkenazi
Intelligence By Gregory Cochran, Jason Hardy,
Henry Harpending ,Department of Anthropology,
University of Utah, Salt Lake City, UT 84112
USA http//homepage.mac.com/harpend/.Public/Ashken
aziIQ.jbiosocsci.pdf Paleoanthropology,
Genetics, Evolution Blog of John Hawks,
Associate Professor of Anthropology, University
of Wisconsin, Madison http//johnhawks.net/weblog/
hawks/hawks.html
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,
Genetic Early Adopters By Emily Singer,
Technology Review, Sept. 8, 2008 file///Users/Eri
c/Desktop/Genomics20Ppt/The20Genetic20Early20A
dopters.webarchive Genomes R Us by Michael
Copeland, Fortune Magazine, Sept. 1, 2008, p. 46
Publications good for keeping up Science,
Nature, Technology Review, Scientific American,
Science News Ray Kurzweils free e-newsletter
http//www.kurzweilai.net/index.html?flash1 iSt
eve.com - Genetics http//www.isteve.com/Articles
_Genetics.htm - Excellent journalist who refuses
to obey P.C. censorship rules