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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.
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.
Types of Mutations
Point Mutations - One base added, deleted, or
substituted for another
Other Types of Mutations
Groups of bases, or whole genes may be added, deleted, inverted,
or copied or moved to new locations
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%
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 carrier’s 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.
Where and when groups of Homo sapiens migrated from Africa,evolving
as they went.
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.
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.
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.
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 almo
surely that of Ghengis Khan.
Ghengis had the most attractive women of each conquered area brought t
him.
He spent much of his time breeding when not conquering.
His numerous sons generally did likewise.
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 sphingolipid 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.
Ashkenazim have won > 23% of Nobel prizes in science and
medicine, tho only ~0.2% of the world’s 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.
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 individual’s 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.
Trends in Cost of Genomic Sequencing
The current price/performance leader is probably the sequencer
Church’s 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 Moore’s
Law for cpu’s 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 < $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.
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.
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)
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.
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
Japan’s errant eugenics policies.
There won’t 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.
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.
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.
Genetics in Medicine, now published monthly, is the official
journal of the ACMG.
http://www.acmg.net//AM/Template.cfm?Section=Home3
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 Moore’s Law. A full sequencing is likely to drop
to ~$1,000 within 5-10 yrs.
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 sh*t about biology!".
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 > 25 years)
Before the Dawn: Recovering the Lost History of Our Ancestors
by Nicolas Wade, 2007, The Penguin Press.
ET, Kodama G, Baldi P, Moyzis RK. 2006.
Global landscape of recent inferred Darwinian selection for Homo sapiens
Proc Nat Acad Sci USA 103:135-140.
1
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/AshkenaziIQ.jbiosocsci.pdf
Paleoanthropology, Genetics, & Evolution
Blog of John Hawks, Associate Professor of Anthropology,
University of Wisconsin, Madison
http://johnhawks.net/weblog/hawks/hawks.html
Genetic Early Adopters
By Emily Singer, Technology Review, Sept. 8, 2008
file:///Users/Eric/Desktop/Genomics%20Ppt/The%20Genetic%20Early%20A
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 Kurzweil’s free e-newsletter
http://www.kurzweilai.net/index.html?flash=1
iSteve.com - Genetics http://www.isteve.com/Articles_Genetics.htm
- Excellent journalist who refuses to obey P.C. censorship rules