Ancestry Flashcards
Story of the human genome (Dunstan)
The story of the human genome is an African one
Human migration + alleles
Human migration carried subsets of geentic diveristy to new locations – each popultons established difefrent frequncies (sometimes popultions will aquire novel variations)
Novel variations
Sometimes popultions will aquire novel variations
Human mutation rate – 0.5 X 10^-9 per BP per meiosis
Allele freuqncies between popupultions
Subset of allles left popultion and founded new popultions –> As each popultion is established there is a different frequencey of allles in each popultion
- All alleles are still founded in Afirca (because we came from there) but in different frequnceies
DIFFERENT HUMAN POPULTIONS HAVE DIFFERENT ALLELE FREQUCNIES
What do genetic tests use
Direct to consumer genetic testing companies take advantage of popultion level allele frequnecies to guess your gentic testing
Guess in Genetic tests
It is a statistical assemnet – NOT guarentee
What do companies offer
- Ancestry reports
- Genotype to phenotype predictions
Ancestory reports of genetic testing
Detemrines the percentage of DNA that orginated from different popultions
- What percent of DNA is from what part of the world
Genotype to phenotyoe predictions in genetic tests
Calculate Disease risks
Predict drug repsonses
Predicts ‘fun’ phenotypes (Bitter taste + earwax type + freckling + height)
What do genetic testing companies sequence
They do not sequence genomes –> since only 0.1% of our genome is varaible –> DTC companies save money by only genotyping SNPs
- Why sequncey all that would be the same –> only look at varaible resghions
- Look at SNPs across genome
- Look at all Autosomes + sex chromsomes
Variability in genome
Only 0.1% of our genome are varaible
What do testing companies look for
You only see what you are looking for –> novel mutations will not be identified
- You won’t see mutations that are not the SNPs looking at
How do companies test DNA?
- ssDNA containing specific SNP variants are bound to
a glass slide (a microarray) - sample DNA is isolated, fragmented and
fluorescently labeled and applied over the entire
slide. - Sample DNA fragments bind to complementary
sequences. - Hybridization efficiencies determined by
fluorescence intensities. - The higher the fluorescence, the higher the
probability that the sample DNA matches the snp on
the array
MINE:
DNA –> Chop up DNA –> Put florucent tag –> put on array – on that array you have DNA on chip –> if the DNA match = DNA binds and get flourecence
Issue = not 100% certain – they all have high percent of C
Haplotype
A set of SNPs found on the same chromosome
Power in genetic testing
Power = not looking at one SNP but looking at set of SNPs
BP between SNP
There might be 100s or 1000s of BP between each SNP
How many Haplotypes do we have
We are diploid so each of us have 2 haplotyoes for any streatch of DNA
P(AT)popA = P(A at SNP1) AND P(T at SNP2)
0.15 X 0.55
P(AT)popB = P(A at SNP 1 in B) AND P(T at SNP 2 in B)
Admixture
Occurs when previously diverged or isolated genetic lineages mix
Many of us are admixtures
Most ancestries
Many of us have complicated ancestries and recombinant genomes
Fruimera Case Study
Great Grandparents – 100% finish
Dad = 50% Finish
She should be 25% finish
The company = predicted that she had finnish ancestry and what region of Finland her ancestry was most likley from
Haplogroup painting
Shows where regions of each chrosmome is from
Shows that crossover occurs because not full chromsome is finish form dad = means that part of the chromsomes had recombination (if no recombination would have full finsih on chromsome – dad had one full finsh chromsome and one full not finsh chromsome –> one of his non-finsih chromsomes crossed over with finish chromsome)
Ancetsry anlysis chnaging
You can do ancestry anlysis two times from the same company and get two different results
- Issue = admixture
- Haplotype chnages – how do you find breaking point of crossover
- Designing algrothsm to predict ancestry is challenging – two chromsomes can have two of the same sequnce at as non recombinatrion
Algorthism is hard – uodate them to find breaking point – uopdate them as they get more data
the DNA doesn’t chnage teh computer software does (reaosn why results can chnage)
Testing algorthm
Algorthism is hard – uodate them to find breaking point – uopdate them as they get more data
the DNA doesn’t chnage teh computer software does (reaosn why results can chnage)
Probability of crossover vs no crossover
Have a lower proabbility with recombination = won’t know haplotype is broken
- hard to know if sequence is due to crossover or not (can have the same sequnce)
add in slide 39
How to define a haplotype
- What are the paternal and maternal alleles
- How long is the haplotype
Building Ancestry Algortithms
Ancestry predictions are
built from training sets of
individuals from known
populations to build
predictive algorithms
Ancestry predictions chnaging
- As training sets and algorithms change, ancestry predictions will change
- Different companies use different SNPs + Different training sets + Different algorthisms
You will likley get difefrent ancestry results from difefrent DTC companies
Why does Fruimera and brother have difefrent amounts of finnish
You would think that they should both be 25% finnish –> Are the not the same because during meiosis get random gamates that are all different
Dad = has 1 finish and 1 non-finnish chromsosomes –> fruimera has less of teh finish chromsomes and the brotehr has more because of recombination
SLIDES
* You received half your DNA from
one parent.
* The egg or sperm that created
you will have different
proportions of your parents
maternal and paternal
chromosomes.
* On average, gametes have equal
percentages of maternal and
paternal chromosomes.
Amount of Ancestral DNA each generation
The amount of ancestral DNA approximatley halves each generation BUT this can vary depending on the exact compistion in a gamete
After 7 generations less than 1% of ancestral DNA is expected BUT ancestral DNA can be lost at earlier generations
Ancestry vs. Ethinicity vs. race
All different
Ancestry – genetic lineage group – has biologic definition
Ethnicity – shared cultural origins
Race – Shared physical + cultural + Social charachtersitics – has no biologic definition
Complex trait example
Example – height – height is controlled by many diferent genes
Tall varaint = found all over the world –> can have a popultion with higher frequncey of tall but there is no region that only has tall
- tall gene os not ONLY found in any one popultion – found in all popultions
Variants in diferent popultions
Tall varaint = found all over the world –> can have a popultion with higher frequncey of tall but there is no region that only has tall
- tall gene os not ONLY found in any one popultion – found in all popultions
DNA for vraaints for tall = found all around the world –> certain regions might have more vraints than other regions BUT these vrainats are not exculsive to any one region (can be found more in one popultion but is still found in all popultions)
Unique varaints
Theer are popultions with unique varaints BUT not everyone in that popultion will have that unique varaint
Genetic varaints that are unique to a popultion cannot be used to define all people in that popultion –> not eveyrone in popultion will have that varaint
Race + biology
Race is real BUT is not genetically supported
Genes + Skin color
At least 6 genes with “main effects” are known to contribute to skin color
and many “modifier” and “epistatic” genes
- get continium of color
There is no magic number or combination of alleles that determines whther someone is perceived or idetofies as black, white etc.
DNA varaints for dark skin
The DNA variants for light or dark skin be found all around the world. Certain regions of the world might have more genetic variants for
dark skin than other regions, but these variants are not exclusive to any one region
- Found in all popultions – not exckusive to 1 popultions –> can’t define skin color based on genetic ancestry
DNA + continenets
No DNA variants have been found that can unambiguously divide people into continental populations.
Ex. Of race + biology
Race is real BUT not genetically support
Ex. Fraternal twins – one is white and one is black
Genetic Variation across popultions
Nearly all of the genetic variation found in European Populations is found in Asian populations.
All of the genetic variation found in Euro and Asian population is found in African populations
