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203.343!Introduction to Personal
Genomics!Week 1!
Austen Ganley, July 16th, 2015
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asa.ac.nz
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Opinion Editorial Assignment 1 Reminder about your first OpEd assignment that is
due on Monday, August 3rd!!! I will set up a Stream assignment submission box
for you to submit to. Read the Opinion Editorial Assignments document for more information!
Your OpEd MUST be between 600 and 750 words and it should have a title (12 words or less) that does not contribute to the word count!
Read the resources and read some OpEds to get an idea of what you are supposed to be doing !
Swapping ideas and providing comment on others OpEds is fine: plagiarism of any sort is not!!
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Mutations What are the different types of mutation that
can occur in the human genome?!
Basically, we can divide them into SNPs, indels, structural changes (insertions, deletions, duplications, copy number variations, inversions), and chromosomal changes (aneuploidy)!
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Mutation Prevalence in Humans If we take these four major categories, what
percent of total variation in the human genome do each of them make up?!
SNPs ! ! ! ! ! !%! Indels ! ! ! ! ! !%! Structural changes ! ! ! !%! Chromosomal changes ! ! !%!
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Mutation Prevalence in Humans Actually hard to estimate:!
SNPs! Indels 1/15th as common as SNPs
(Lynch, 2010 PNAS 107:963-)! Structural changes more or less common
than SNPs? ! Chromosomal changes probably close to
zero in human populations (but different in cancer)!
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Zarrei et al 2015 Nature Reviews Genetics 16:172
SNPs CNVs
International SNP Map Working Group Nature 2001 409:928
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Database of Genomic Variantshttp://dgv.tcag.ca/dgv/app/home?ref=
Is a single structural variant of 100,000bp the same as 100,000 single nucleotide mutations?!
We will focus on SNPs, but dont forget that they are far from the only type of mutation!!!
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SNPs SNPs = single nucleotide polymorphisms! Polymorphisms = arbitrarily defined as
mutations present in 1% or more of the population!
It is estimated that every non-lethal mutation currently exists somewhere in the human population!
However, the number of polymorphic sites is much smaller!
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Haplotypes and Haplotype Blocks
https://kristenramirezevolution.wordpress.com/2014/11/25/omg-karen-you-cant-just-ask-people-why-theyre-white/
What does this mean??
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What are haplotypes and haplotype blocks?
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Why Population Variation? What is a population?!!! Where do new mutations come from in a
population?!
Why do mutations change their frequency in a population?!
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Origin of new mutations New mutations through mutation and
migration are easy to understand (I hope!)!
Understanding how mutations change in frequency in populations is more complicated, therefore we will focus on this!
But dont lose sight of the origins of mutation!!
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Selection Different populations live in different habitats,
therefore the selection pressures will be different! This results in differences in what is selected for
(adaptive) and what is selected against (deleterious) between different populations!
Classic example is lactose intolerance in humans!
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Curry 2013 Nature 500:20On Stream as evolution_lactose_tolerance13
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Neutral Drift Mutations arise by chance in individuals! Many of these mutations are neutral, or nearly-
neutral! Certain individuals will contribute more or less to
the next generation than others, and so on! Therefore their alleles will increase or decrease
in frequency accordingly, even though they may have no phenotypic effect (or no effect on fitness)!
The Genghis Khan effect.. (http://www.nature.com/news/genghis-khan-s-genetic-legacy-has-competition-1.16767)!
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Zerjal et al, 2003 American Journal of Human Genetics 72:717On Stream as Genghis_Khan_genotype03
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Bottlenecking Bottlenecking is an extreme example of drift! Usually it is thought that a new population is
established from a small number of individuals from an existing population the founder population!
As you know, small population sizes give a greater chance for drift, so founder populations, by chance, can have different allele frequencies to the originating population!
This is also called the founder effect!
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http://www.nature.com/scitable/topicpage/genetic-drift-and-effective-population-size-772523
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Balancing Selection Balancing selection is said to occur when
selective forces act to maintain different alleles at a greater frequency in the population than that expected just by mutation!
Therefore, this is actually a way that variation is maintained (rather than created or changed) in a population!
There are two common forms of balancing selection:! Heterozygote advantage (overdominance)! Frequency-dependent selection !
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Heterozygote Advantage As it says sickle cell anaemia is the classic
example!
http://www.nslc.wustl.edu/sicklecell/part3/biogeography.html
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Frequency-Dependent Selection Where the more rare an allele is, the greater its
fitness! Therefore, common alleles become more rare,
and rare alleles become more common, and around again!
For example, tattoos or fashion(?!?!?)! Proposed to explain the genetic variation seen in
the major histocompatibility locus in humans (and other species)!
However, little strong evidence of examples of it in humans !
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Haplotypes and Haplotype Blocks
https://kristenramirezevolution.wordpress.com/2014/11/25/omg-karen-you-cant-just-ask-people-why-theyre-white/