Download Tracing Human Evolution with Genetics (Haplotypes)

Tracing Human
Evolution with
Genetics
SELECTION
June 9-17, 2007
SNPs

Single Nucleotide Polymorphisms
May or may not be in coding regions
 May or may not cause phenotypic
changes
 Frequency of SNP distribution varies

Seq 1
Seq 2
Seq 3
ATCGG ATCCA TGTAT CGATT
ATGGG ATGCA TGTAT CGATT
ATCGG ATGCA TGAAA CGATT
Haplotype



Refers to either:
 Genetic makeup of one set of chromosomes
 An area of a chromosome defined by a set of
associated SNPs
Based on statistical analysis and measurement of
linkage disequilibrium (LD)
Sources of LD
 Recombination
 Genetic linkage
 Random drift
 Non-random mating
 Interactions between genes
 Population structure
Important points…
Correlation of a SNP and a phenotype
is just that – a correlation, not
necessarily a cause.
 Haplotypes often identify genes
involved in polygenic traits.

No single site controls the phenotype.
 Quantitative trait loci (QTLs) are
genetic areas involved in modulating
expression of polygenic traits.

Haplotypes and Evolution



Recent human evolution is visible in the
genome as “selective sweeps”.
Selective sweeps are identified based on
LD and haplotypes.
Articles:


Localizing Recent Adaptive Evolution in the
Human Genome
Convergent adaptation of human lactase
persistence in Africa and Europe
Lactase Persistence and
Pastoralism

Positive selective pressure
Liquid
 Protein


Subsequent migration and spread of
phenotype
Northern Europeans to North America
 Southern migrations through Africa

Lactase Persistence
Lactose malabsorption
 Lactose tolerance
 Lactase Persistence


Continued expression of lactasephlorizin hydrolase (LPH) in mammals
past weaning
Global Distribution of
Lactase Persistence

Europeans



Asian



High levels in Scandinavians
Decreasing levels further south in Europe
Generally low levels in tested populations
High in Khazaks
African


High in Tutsi and Fulani
Low in other groups
Genetics of Lactase
Persistence

Northern
Europeans



SNP identified
Enhanced
expression of
lactase gene
Africans

Not the same
SNP
Lactose Tolerance Test
Fast for 8-12 hours
 Ingest 50g lactose
 Take blood samples for two hours and
test for a rise in blood glucose levels
 Caveats:

Fasting?
 Field conditions: Used finger pricks
and strips for monitoring diabetes

Evolutionary Medicine



Many common medical issues are
polygenic
Traditionally required a large affected family
to identify candidate genes
Genome Wide Association (GWA) Articles


Genome-wide association study of 14,000
cases of seven common diseases and 3,000
shared controls.
Guilt by association
Case



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A medical researcher is interested in the underlying
causes of type II diabetes. Specifically, why do
different people have different tendencies to develop
diabetes? Obviously current lifestyle will have a major
impact, but lifestyle is not a complete explanation.
What about genetic history? Is there a way to use
tools such as the HapMap or genome-wide association
surveys to predict risk for populations and individuals?
How might this be useful for helping an American of
mixed ancestry understand their risk for developing
diabetes?
Would it be useful for a Han Chinese person?
What are the ethical considerations of collecting and
using this kind of information?