l l l ll l l 0.4 inbreeding human populations from dna 0pima mixe mixtec zapotec mayan piapoco surui...
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Measuring relatedness inhuman populations from DNAAlejandro Ochoa, John D. Storey Lab, Princeton University7 DrAlexOchoa � viiia.org/research/ R [email protected]
Why study relatedness?
Human geneticsis fascinating!
Search fordisease-causinggenetic variants
Heritability ofcomplex traits
Animal and plantbreeding
The kinship coefficient for parent-child: 14
The kinship coefficient for siblings: 14 on average
Visscher et al. (2006)
The inbreeding coefficient in populations
Measurements relativeto a reference pop.:
Inbreeding = 0 in thelocal population
Inbreeding ≥ 0 relativeto a distant ancestralpopulation
Better measured usingcovariance
Recently admixed populations
African-Americans
Baharian et al. (2016)
Hispanics
Moreno-Estrada et al. (2013)
Kinship model for genotypes
symbol meaningT ref ancestral populationi locus index
j , k individual indexespTi ref allele frequencyxij genotype (num ref alleles)ϕTjk kinship of j , k
f Tj inbreeding of j
Statistical model:
E[xij |T ] = 2pTi ,
Var(xij |T ) = 2pTi(1− pTi
)(1 + f Tj ),
Cov(xij , xik |T ) = 4pTi(1− pTi
)ϕTjk .
(Wright 1921, 1951; Malécot 1948; Jacquard 1970).
We developed a new kinship estimation framework that works forarbitrary population structures!
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New kinshipestimates
Genotypes from “Human Origins” (Lazaridis
et al. 2014, 2016)
By Ephert [CC BY-SA 3.0], via Wikimedia
Commons
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−0.0
50
0.05
0.1
0.15
Kin
ship
Standard kinshipestimates
Genotypes from “Human Origins” (Lazaridis
et al. 2014, 2016)
By Ephert [CC BY-SA 3.0], via Wikimedia
Commons
Population-level inbreeding
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0.2
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Inbr
eedi
ng
Indi
vidu
als
0.0
0.5
1.0
Individuals
Anc
estr
y fr
ac.
00.
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20.
30.
4
Kin
ship
x
PU
RC
LMP
EL
MX
L
Pop
ulat
ion
x
AF
RA
MR
EU
R
Anc
estr
y
Kinship driven byadmixture in Hispanics
New kinship estimates
Genotypes from the 1000 Genomes Project (2012)
AcknowledgmentsJohn D. StoreyAndrew BassIrineo CabrerosChee ChenWei HaoEmily NelsonRiley Skeen-Gaar
Neo Christopher ChungInstitute of InformaticsUniversity of Warsaw
Funding:National Institutes of HealthOtsuka Pharmaceuticals
Lewis-Sigler Institute for Integrative Genomics