Transcript What information goes into Results?

Bioethics in Daily Life
Day 3
ANT 4930
Prof. Connie J. Mulligan
Department of Anthropology
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This week - Race
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Race
Is there a biological basis to race?
How have we evolved?
Global distribution of genetic and phenotypic variation
How different are we?
Genetic ancestry
Racial disparities in health
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Required reading (also listed on course webpage, Day 2)
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http://en.wikipedia.org/wiki/Race_and_genetics – Wikipedia entry on ‘Race and Genetics’
http://www.pbs.org/race/000_About/002_04-background-01-07.htm - Race: The Power of an
Illusion, interview with Alan Goodman
Sample Genetic ancestry report, intended for an African American audience
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Video – African American Lives
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Practice oral presentations
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Next week – Genetic screening/genetic
testing and ancestry estimation
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Prenatal screening
Testing for personality, mate choice, etc
Genetic ancestry testing
Reproductive technologies
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Who is the mother when egg and sperm are donated?
Required reading (also listed on course webpage, Day 3)
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http://www.newsweek.com/2010/06/09/inside-information.print.html - Newsweek article, Americans want to
know their genetic codes
http://www.technologyreview.com/blog/editors/25297/ - Genetic testing can change behavior
http://www.nature.com/ng/journal/v42/n10/pdf/ng1010-811.pdf - newborn genetic screening
http://www.nature.com/nature/journal/v466/n7308/pdf/466816a.pdf - Nature, Aug 12 2010, Genetic testing
regulation
http://www.time.com/time/magazine/article/0,9171,1158968-2,00.html – Iceland genetics project
http://www.medicalnewstoday.com/articles/157335.php - Iceland/deCODE project - genes identified to date
Skim http://bioethics.georgetown.edu/pcbe/reports/beyondtherapy/ - Beyond Therapy: Biotechnology and
the Pursuit of Happiness, report from the President’s Council on Bioethics, 2003 (353 pages)
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Video – African American Lives
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Four oral presentations
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NPR show, Is there a biological
basis for race?
Talk of the Nation, Jan 15, 2010
http://www.npr.org/player/v2/mediaPlayer
.html?action=1&t=1&islist=false&id=1226
20064&m=122620043
C. Mulligan, Copyright 2011
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C. Mulligan, Copyright 2011
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What is race?
• Is race a purely cultural construct or is there some
biological or genetic distinction between races?
• There is no Caucasian gene, no African gene, no Asian
gene
• Is there one gene that distinguishes one race from
another? No.
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Human evolution and
genetic variation
• There are no ‘pure’ human stocks and there never were
• No populations are more highly evolved than others
• Human populations are too closely related to be
considered subspecies
• There is a continuum of genetic variation across the globe
• Very little time has passed since anatomically modern
human evolved, i.e. little variation within and between
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populations
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A little terminology
• Genetics is the study of
heredity and variation of
organisms
• A gene is a piece of DNA
that is responsible for the
inheritance of a specific
characteristic
– eye color
– ability to process lactate
(drink milk)
• Gene  protein
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Human karyotype (chromosomes)
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What is DNA?
• DNA is a blueprint to
direct the production
of proteins
– Coding = genes (~3%)
– Non-coding (~97%)
• DNA can be thought of
as a sequence of
letters (nucleotide
bases)
– Adenosine = A
– Guanine = G
– Cytosine = C
– Thymine = T
Genetics, 2001, Hartl and Jones,C. Mulligan, Copyright 2011
Jones and Bartlett Publishers, Inc All rights reserved
What genes do we have?
• No one has ever identified a gene for:
– Intelligence
– Athleticism
– Musical ability
– Language ability
– Work ethic
– Personality
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What is a genetic variant?
This genetic variant is a change from a C to a T
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How do you interpret a genetic
variant?
• What does a C-to-T
change mean?
• Smarter, prettier,
faster, stronger???
– No, just different
• Most variants are
neutral = no effect
– Genes make up only
~3% of genome and
genes make our
phenotype
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Human variation
• There are differences between
people
– Phenotypically
– Genetically
• What do the differences mean?
• Genetic differences are studied
through molecular analysis
– Does a variant have an effect?
• Does it occur in a gene?
• Does if change the protein?
• What does the protein do?
– Or is it just variation?
Genetics, 2001, Hartl
and Jones,
C. Mulligan,
Copyright 2011
Jones and Bartlett Publishers,
Inc
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Genetic variation in
humans around the
world
• Phylogenetic analysis of
non-coding, neutral region
• 1st divergence
– African cluster = common
human origin
• Subsequent divergences
– People from around the world
are mixed together
– No divisions based on race or
geography
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Cann et al., Nature, 1987
• What about sickle-cell anemia? That’s only in Africans!
• Not so. Sickle cell anemia is correlated with areas of
malaria, i.e. Africa, Asia, and Europe
– Sickle cell anemia protects against malaria = positive selection
Genetics, 2001, Hartl and Jones, Jones and Bartlett Publishers, Inc
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But we look different!
• We can see differences between people
– e.g. dark-skinned, light hair, etc
• But, only a few genes determine skin color, hair
color, etc. so it doesn’t take many variants to make
us look different
– The differences are literally only ‘skin deep’
– Skin color is controlled by levels of melanin
– Three main candidate genes for melanin production
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Skin color
• Skin color shows some geographic patterning
– Does it correlate with race?
Distribution of different skin colors in indigenous populations of the world (Jobling et al. 2004)
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What about another phenotype, like the
ability to drink milk/digest lactose?
Is there geographic patterning that matches race categories?
Frequency of lactase persistence around the world
Fig 13.10, Jobling et al. 2004
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It seems like we see some phenotypes
patterned across the world in ways
that could possible correlate with race
• But, only a few genes determine skin color, hair color, etc. so those genes aren’t
representative of the entire genome
• 88% of skin pigment variation is apportioned among populations (Relethford
2002)
– In contrast, only 10-15% of average genetic variation is apportioned among
populations
• Furthermore, only skin pigmentation shows a good correlation with geography,
or latitude (Parra 2007)
– Variation in hair and iris color is much more restricted
• Most humans have dark hair and irises
• Red and blond hair are mainly found in Europe
• Lighter iris colors (blue, green, hazel) are mainly found in Europe, and some in the Middle
East, North Africa, West Asia and South Asia (Sturm and Frudakis 2004)
• So, we’re talking a handful of genes that control skin pigmentation that correlate
with geography, and possibly race
– Is that enough to say there’s a biological or genetic basis to race?
• What if we look at neutral (non-gene-encoding) DNA?
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Using current
analytic methods
and huge
datasets, we can
distinguish
between
populations in
astonishing detail,
far beyond ‘races’
A statistical summary of > ½ million genetic variants from 1,387 Europeans based on principal component
axis one (PC1) and axis two (PC2). Small colored labels represent individuals and large colored points
represent median PC1 and PC2 values for each country. PC axes are rotated to emphasize similarity to the
geographic map of Europe. AL, Albania; AT, Austria; BA, Bosnia-Herzegovina; BE, Belgium; BG, Bulgaria; CH, Switzerland; CY,
Cyprus; CZ, Czech Republic; DE, Germany; DK, Denmark; ES, Spain; FI, Finland; FR, France; GB, United Kingdom; GR, Greece; HR,
Croatia; HU, Hungary; IE, Ireland; IT, Italy; KS, Kosovo; LV, Latvia; MK, Macedonia; NO, Norway; NL, Netherlands; PL, Poland; PT,
Portugal; RO, Romania; RS, Serbia and Montenegro; RU, Russia, Sct, Scotland; SE, Sweden; SI, Slovenia; SK, Slovakia;
TR, Turkey;
UA,2011
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What about differences in disease rates?
• Lots of evidence that AfricanAmericans and Hispanics suffer
disproportionately from diabetes,
obesity, high blood pressure, some
types of cancer, etc.
• Unclear how much is due to
environment and how much to
genetics
– Popular press – may focus on ‘racial’
differences
– Research and clinical practice – unclear
that ‘racial’ differences exist or are
sufficiently large to affect treatment
• Starting to dissect population
differences in disease and
response to treatment
Source: National Center for Health Statistics (2004)
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Complex disease rates vary worldwide
Example - Differences in cancer rates and types
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Heredity? Behaviors? Other Factors?
• Study people who move from one
country to another
• Result – exposure to risk factors
for cancer vary by geographic
location
– Japan – low rate of colon cancer
– US – low rate of stomach cancer
– When Japanese move to the US, their
rate of colon cancer increases and
stomach cancer decreases
– Obviously no correlation with ‘race’
--National Institutes of Health
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Pharmacogenomics
• Goal of research is to use genetic differences to benefit
the population and the individual
• Pharmacogenomics is the idea that a health plan can be
tailored to an individual’s unique genetic structure
• Currently, only look at broad categories, such as ‘race’
– Blacks are more likely than whites to suffer side effects from certain
antidepressant drugs
• Blacks have a higher frequency of one variant that reduces the liver’s ability to break down
certain tricyclic antidepressant drugs, so individuals with that variant will suffer more side
effects
– Blacks may need lower levels of certain antidepressants (e.g. Prozac)
• Blacks have a higher frequency of a genetic variant that increases the speed at which a
newer class of antidepressants (Prozac) take effect
– Black males may process testosterone more quickly, resulting in
stronger bone and an increased risk of prostate cancer
– Whites experience more side-effects with warfarin, a blood-thinning
drug, than Blacks
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Devilish details
• Warfarin example
– 8% Whites carry a genetic variant that causes trouble with
warfarin, blood-thinning drug
– 2-3% Blacks carry same mutation
• Would your doctor make a different diagnosis or
propose different treatment based on knowledge of
your race? No.
• Difference is only significant when looking at
populations, not when looking at an individual
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"Nobody would make clinical decisions
based on a racial profile. Race is a very
crude predictor of any sort of differential
response to medication”
Dr. Bruce Pollock, chief of geriatrics and
neuropsychiatry, University of Pittsburgh,
Department of Psychiatry
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If not race, what then?
• Doctors should base all diagnoses and
treatments on all available information
• They should take detailed family histories
that capture the full range of an
individual’s genetic and ethnic make-up
– Not a single indicator, like race
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What about forensics?
• Forensic scientists can look at a skeleton and
determine, with some accuracy, if the
individual was Black, White, Asian, Native
American, etc
– How is that possible?
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Bottom line
• The vast majority of the human genome does not match
racial categories
• However, there are phenotypes that can be used to
distinguish between races
• Furthermore, if we use enough genetic variants, and
variants that are maximally informative in a geographic
sense, we can distinguish between populations from
different races, different continents, different countries
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How to read a journal article
• What are the parts of a journal article?
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Parts of an article
– some of this information is very field-specific and
may not be true outside Bioanthropology
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What is an abstract?
What information goes into an Intro?
What information goes into Results?
What information goes into Disc?
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Parts of an article
• What is an abstract?
– A summary of points presented in skeletal form
– Opportunity for authors to specify what they think
are the most important points
• What information goes into an Intro?
• What information goes into Results?
• What information goes into Disc?
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Parts of an article
• What is an abstract?
• What information goes into an Intro?
– Background info
– Foreshadows Discussion
– All Intro material should be followed up later in article
• What information goes into Results?
• What information goes into Disc?
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Parts of an article
• What is an abstract?
• What information goes into an Intro?
• What information goes into Results?
– Just Results
– No interpretation, no discussion
• What information goes into Disc?
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Parts of an article
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What is an abstract?
What information goes into an Intro?
What information goes into Results?
What information goes into Disc?
– Interpretation and significance of results
– Opportunity for authors to focus on what they think is
most important about their results
– Should pick up on info in Intro
– Can be very dependent on what topics are currently
‘hot’ so Discussion can become outdated even if
Results are still relevant
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How to read a journal article
• Note year of publication
– Anything more than 5 yrs old is fairly old in my field
• Note authors
– Have you read anything else by this lab?
– Author et al. Year is the best way to refer to a paper
• Refer to articles this way in Questions/Comments, Journal Analysis,
exam, etc
• General strategy for an article outside of your field
– Read Abstract, then Intro and then Disc
– M&M is usually too complicated unless you want a specific
piece of info
– Results is generally pretty cut and dried
– Re-read abstract after you read paper
• See what authors presented as the take-home message
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How to remember and
understand a journal article
• Take notes while reading
• Re-read article until you really understand it
• Make summary notes when you are finished reading
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What was purpose of study?
What questions were being asked?
What were final answers?
What was unique about the study?
What is the next step?
• Write notes on paper itself or on notecards or
electronically
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