vab11 06a population genetics
DESCRIPTION
hbhkjTRANSCRIPT
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Population genetics
sexual reproduction genetic structure of population Hardy-Weinberg law factors disturbing Hardy-Weinberg equilibrium human populations
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Population genetics
the studies of genetic structure of population the studies of events affecting population the studies of relationships inside population, relationships
between populations the studies of population dynamics in population studies, we always need a cross section
of the population
population is a collection of individuals who belong to 1 species; all these individuals occupy (share) a common area
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Sexual reproduction and genetic structure of population
autogamy
allogamy inbreeding outbreeding panmixia
model of ideal population distribution of allele and genotype frequencies according to
Hardy-Weinberg law
in plants only
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male & female gametes from 1 individual give rise to zygote
during few generations, autogamy leads to high level of homozygosity in offspring
generation heterozygotes (%)
homozygotes (%)
autogamy
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allogamy
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male & female gametes from 2 individuals give rise to zygote
allogamy
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Sexual reproduction and genetic structure of population
allogamy inbreeding
mating between consanguineous individuals along subsequent generations
inbreeding results in decrease of genetic heterogeneity in population it has similar effect as autogamy (but autogamy acts more rapidly)
in human, consanguineous mating is very similar to (or the same as) inbreeding
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Sexual reproduction and genetic structure of population
allogamy outbreeding
mating between individuals who are not closely related outbreeding results in maintenance of genetic
heterogeneity in population in human: a marrying outside one's social group
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Sexual reproduction and genetic structure of population
allogamy panmixia a model of ideally panmictic population:
random mating among individuals in population; individuals of the same generation mate together
individuals of all genotypes are equally fertile there is no selection among various genotypes
no mutations originate there is no migration the population is large enough
the ideally panmictic population does not exist in real
world it is a mathematical description of simplified model
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Genetic structure of population
gene pool: a collection of all the alleles at a particular locus for the entire population
gene pool: for autosomal loci, the size of the gene pool is twice the number of individuals in the population
AA
AA
AA
AA
AA
Aa
Aa Aa
Aa
Aa Aa
Aa Aa
Aa
Aa
Aa Aa
Aa Aa Aa Aa
Aa Aa
Aa
Aa
Aa
Aa
Aa Aa Aa aa
AA
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Genetic structure of population
is specified by allele frequencies and genotype frequencies in population: allele frequency: relative proportion of particular allele
in population genotype (phenotype) frequency: relative proportion
of particular genotype (phenotype) in population
we must distinguish 2 basically different situations if we
need to estimate allele and genotype frequencies: co-dominance & semidominance complete dominance
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Genetic structure of population autosomal inheritance I. co-dominance, semidominance:
genotype & phenotype frequencies
each genotype can be distinguished from others according to its specific phenotype
the frequencies of all genotypes can be determined accurately
AA AA
Aa Aa
aa aa
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Genetic structure of population autosomal inheritance I. co-dominance, semidominance:
genotype & phenotype frequencies
phenotype frequencies are equal to corresponding genotype frequencies
we can simply count individuals of all genotypes after this, we can calculate allele frequencies:
AA
AA
AA
AA
AA Aa Aa Aa
Aa
Aa
Aa Aa Aa Aa
Aa
Aa Aa
Aa Aa Aa Aa
Aa Aa Aa
Aa Aa
Aa
Aa Aa Aa aa
AA
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Genetic structure of population autosomal inheritance I. co-dominance, semidominance:
genotype & phenotype frequencies
AA
AA
AA
AA
AA Aa Aa Aa
Aa
Aa
Aa Aa Aa Aa
Aa
Aa Aa
Aa Aa Aa Aa
Aa Aa Aa
Aa Aa
Aa
Aa Aa Aa aa
AA
frequency of allele A: 25 A 2 x 6 A +
6 individuals carry 2 alleles A (homozygotes)
total count of all alleles of the gene in the population
25 individuals carry 1 allele A (heterozygotes)
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Genetic structure of population autosomal inheritance I. co-dominance, semidominance:
allele frequencies
we can calculate allele frequencies directly from frequencies of corresponding phenotypes:
2.n(aa)2.n(Aa)2.n(AA)n(Aa)2.n(AA)fA ++
+=
n ... number of individuals with certain phenotype
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Genetic structure of population autosomal inheritance II. complete dominance:
genotype & phenotype frequencies
the only one genotype that we can distinguish from others: recessive homozygotes always differ in phenotype from all other individuals
the frequency of recessive homozygotes is the only one frequency that can be determined accurately
AA AA
Aa Aa
aa aa
AA AA AA
AA
AA
Aa
Aa Aa
Aa
Aa
Aa
Aa Aa Aa
Aa
Aa Aa
Aa Aa Aa Aa
Aa Aa Aa Aa Aa
Aa
Aa Aa Aa aa
AA Aa Aa
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Genetic structure of population autosomal inheritance II. complete dominance:
genotype & phenotype frequencies all other frequencies (genotype & allele frequencies)
must be calculated according to Hardy-Weinberg law
H.-W. law can be applied exactly in ideally panmictic populations (see above mentioned conditions in ideal panmixia)
although ideally panmictic population does not exist, we can apply mathematical equations of H.-W. law to common populations (the error of such calculation is usually acceptable)
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Hardy-Weinberg law
Hardy-Weinberg law describes distribution of alleles and genotypes in panmictic population:
p + q = 1
p2 + 2pq + q2 = 1
allele frequencies:
genotype frequencies:
relative proportion of particular alleles in population
relative proportion of particular genotypes in population
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Hardy-Weinberg law: Genotype frequencies
AA
AA
AA
AA
AA
Aa
Aa Aa
Aa
Aa
Aa
Aa Aa Aa
Aa
Aa Aa
Aa Aa Aa Aa
Aa Aa
Aa
Aa Aa
Aa
Aa Aa Aa aa
AA
relative proportion of dominant homozygotes
relative proportion of heterozygotes
+ + relative proportion of recessive homozygotes
= entire population (100 % of individuals)
p2 + 2pq + q2 = 1
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Hardy-Weinberg law
the probability of allele transfer to gametes (in the context of entire population) depends on frequency of this allele in particular population
more frequent allele in population higher probability of allele transmission into offspring
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Hardy-Weinberg law the probability that 2 independent events would meet together
(i.e. egg carrying particular allele would meet sperm cell with particular allele) is equal to multiplication of probabilities of occurrence of these 2 independent features
frequency of allele A
(p)
frequency of allele a
(q) frequency of allele A
(p)
frequency of AA (p2)
frequency of Aa
(pq) frequency of allele a
(q)
frequency of Aa
(pq)
frequency of aa (q2)
dominant allele frequency : p recessive allele frequency: q
probability of meeting gametes (oocyte & sperm cell) with particular alleles:
spermatozoa:
egg cells:
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Hardy-Weinberg law
p2 + 2pq + q2 = 1 genotype frequencies in population:
frequency of allele A
(p)
frequency of allele a
(q) frequency of allele A
(p)
frequency of AA (p2)
frequency of Aa
(pq) frequency of allele a
(q)
frequency of Aa
(pq)
frequency of aa (q2)
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H.-W. law: consequences
if there are established conditions for H-W equilibrium in population allele & genotype frequencies remain unchanged
if there is H-W equilibrium in population it is possible to calculate frequency of recessive allele from the frequency of recessive homozygotes
it is possible to calculate all other frequencies (dominant allele frequency and genotype frequencies) from the frequency of recessive allele
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H.-W. law: consequences
low allele frequency in population: lower frequency of corresponding homozygotes rare alleles are found in heterozygotes mainly
(in the case of recessive disorders, most of people who have this allele are carriers only; sick people are found rarely):
allele frequency (q)
heterozygote frequency (2pq)
homozygote frequency (q2)
0,5 0,5 0,25
0,2 0,32 0,04
0,1 0,18 0,01
0,01 0,02 0,000 1
0,001 0,002 0,000 001
0,000 1 0,000 2 0,000 000 01
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Simplification of H.-W. law
it can be used if the frequency of particular phenotype in population is less than 1:10 000 (rare traits or diseases): q2
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H.-W. law: Gonosomal genes in population
X-linked traits (genes) 2 different situations that can be found in population:
women men
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H.-W. law: Gonosomal genes in population
WOMEN: 3 possible genotypes (XHXH, XHXh, XhXh) allele frequencies & genotype frequencies may be
calculated according H.-W. rule (as in the case of autosomal genes)
women: recessive phenotype frequency (XhXh) : q2
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H.-W. law: Gonosomal genes in population
MEN: 2 possible genotypes (they are hemizygotes) (XHY, XhY) probability of hemizygote (XhY) origination is equal to
probability that single allele would be inherited from mother
allele frequencies = genotype frequencies !!!
men: recessive phenotype frequency (XhY) : q
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Hardy-Weinberg equilibrium
it is a state of population if there are met all conditions of ideally panmictic population
thus, H-W equilibrium is a steady state of population: there are no changes in population
NO EVOLUTION
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Sexual reproduction and genetic structure of population
panmixia a model of ideally panmictic population: random mating among individuals in population; individuals
of the same generation mate together
individuals of all genotypes are equally fertile there is no selection among various genotypes
no mutations originate there is no migration the population is large enough
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Equilibrium in population
equilibrium is a steady state of population genetic structure of population remains unchanged (genetic structure of subsequent generations remains the same ...)
H-W equilibrium: only in the case when there are met all conditions of ideally panmictic population (thus, no selection acts on individuals, ...)
any kind of selection some other equilibrium may be established in population new equilibrium is established if selection remains the same
through subsequent generations (the same intensity, the same preference of particular phenotypes, ...)
changes in selection changes in population equilibrium balanced polymorphism: special type of equilibrium
in population (see later)
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Factors disturbing Hardy-Weinberg equilibrium
non-random mating selection acting on particular phenotypes migration occurs (immigration / emigration) new mutations originate population is small genetic drift
(bottleneck effect, founder effect)
changes in allele frequencies
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Factors disturbing Hardy-Weinberg equilibrium non-random mating
assortative mating the choice of a partner because the partner possesses some
particular trait (traits) usually positive effect some genetic disorders: negative effect (people suffering
from some disorder tend to choose a partner with similar medical problems)
stratification stratified population contains a number of subpopulations that are
genetically isolated one from another e.g.: U.S. population is stratified:
2 major subpopulations (Caucasians & African Americans) other subpopulations: Native Americans, Asians, Hispanics
there is strong mating preference: partner is usually chosen inside particular subpopulation
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
selection acts directly on phenotypes !!! through successful phenotypes, particular alleles are
transmitted into offspring individuals of various phenotypes can have different fitness:
various ability to survive various number of children fitness of particular phenotypes can vary from 0 to 1:
0 no child of particular phenotype survive to reproductive age 1 all children of particular phenotype survive to reproductive age
coefficient of selection: s = 1 - f
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
selection against unfavourable dominant allele this allele is expressed in each individual selection acts on all individuals who have the allele
selection against unfavourable recessive allele this allele is expressed only in homozygotes the allele is not seen in phenotype in heterozygotes
selection do not act on heterozygotes
selection can not work against alleles causing diseases with late onset
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
balanced polymorphism (heterozygote advantage)
AS AS
AS
AS
AS
AS AS
AS
AS
AS
AS
AS
SS AA
AA
AA
AA SS
SS
SS
AA
AA
SS
SS
p2 = 0,25 q2 = 0,25 2pq = 0,50
frequency of allele S matches to frequency of genotype SS
ZYGOTES:
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
balanced polymorphism (heterozygote advantage)
AS AS
AS
AS
AS
AS AS
AS
AS
AS
AS
AS
SS AA
AA
AA
AA SS
SS
SS
AA
AA
SS
SS
p2 = 0,25 q2 = 0,25 2pq = 0,50
frequency of allele S matches to frequency of genotype SS
children:
malaria sickle-cell
disease
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
balanced polymorphism (heterozygote advantage)
Selection for heterozygotes (heterozygous advantage): in certain conditions, deleterious allele S is selectively maintained in heterozygotes & the same allele S is selectively eliminated in homozygotes.
AS AS
AS
AS
AS
AS AS
AS
AS
AS
AS
AS
children:
AA
AA
AA SS
SS SS
p2 = 0,17 2pq = 0,67 q2 = 0,17
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
balanced polymorphism (heterozygote advantage)
p2 = 0,17 2pq = 0,67 q2 = 0,17
AS AS
AS
AS
AS
AS AS
AS
AS
AS
AS
AS
AA
AA
but: p=0,5 q=0,5 allele frequency
genotype frequency
AA SS
SS SS
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
any change in selection factors fitness of particular phenotypes may be changed:
e.g.: allele HbS is frequent in human population occupying certain malaric area; heterozygotes (genotype HbA HbS) are preferred by selection
mosquitoes (vectors of malaria disease) do not live there any more
swamps were dried out
allele HbS lose its advantage for heterozygotes heterozygotes (HbA HbS) lose the advantage HbA HbA individuals have the highest fitness frequency of allele HbS decreases in population
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Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes
selection factors
differentiated fitness & reproduction ability of individuals with
different phenotypes
adaptive change of genetic structure
of population
optimalization of phenotypes
evolution
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Factors disturbing Hardy-Weinberg equilibrium migration
immigration emigration
migration introduction of new alleles into population e.g.: mutant alleles causing phenylketonuria (PKU):
the most common mutations are of Celtic origin migration of the Celts spreading of alleles into other
populations frequency of these alleles over the world reflects migration of
Celts incidence of PKU:
Ireland: approx. 1/4500 (lower frequency in Southern Europe)
gene flow
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Factors disturbing Hardy-Weinberg equilibrium mutations
new mutations originate new alleles originate
e.g.: -thalassemia:
mutations in -globin gene are responsible for the disease there are known numerous different alleles causing
-thalassemia in different region, different mutations originated ...
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift: fluctuation in allele & genotype frequencies from generation
to generation due to incomplete transmission of particular alleles from generation to generation (alleles are transmitted proportionally only in the case of large population ... law of statistics)
less frequent allele can be lost from population
bottleneck effect founder effect
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift bottleneck effect
AA
aa
aa
aa
aa
aa
aa
AA
AA AA
aa
aa
Aa
Aa
Aa
Aa
Aa aa
Aa
Aa
Aa
Aa
Aa
aa
Aa
Aa
Aa
Aa
Aa
aa
Aa
Aa
Aa
Aa
Aa aa
Aa Aa
aa
Aa
Aa
Aa Aa
aa
Aa
Aa
Aa
Aa
Aa
Aa
Aa Aa
Aa
Aa
Aa Aa
aa aa
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift bottleneck effect
aa AA
AA
Aa
Aa Aa
Aa
Aa Aa
Aa
Aa
Aa
Aa
Aa
Aa
Aa
Aa
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift founder effect
AA
Aa AA
AA
AA
AA
AA
AA AA
AA
AA
AA AA AA
AA
AA AA
AA
AA
AA
AA
Aa
AA
AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA
AA
AA
AA AA
AA AA AA
AA
AA
AA
AA
AA
AA
AA AA
AA
AA
AA
AA
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift founder effect
AA
AA AA
AA
AA
AA AA
AA
AA
AA AA AA
AA
AA AA AA
AA
AA
Aa
AA
AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA
AA
AA AA
AA AA AA
AA
AA
AA
AA
AA
AA
AA AA
AA
AA
AA
Aa AA
AA
AA AA
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift founder effect
e.g.: European settlers in North America, South Africa ...
AA
AA AA
AA
AA
AA AA
AA
AA
AA AA AA
AA
AA AA AA
AA
AA
Aa
AA
AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA AA
AA
AA
AA
AA
AA AA
AA AA AA
AA
AA
AA
AA
AA
AA
AA AA
AA
AA
AA
Aa AA
Aa
AA aa
AA Aa
Aa
Aa AA
AA
Aa
AA
AA
AA
aa Aa
AA AA
AA
AA AA
AA AA
AA
AA
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift founder effect Old Order Amish:
a religious isolate of European descent that settled in Pennsylvania
immigrants gave rise to a number of small, genetically isolated subpopulations throughout USA & Canada
the Amish tend to have large families (even single carrier present in community can transmit particular allele into a large number of children)
they marry Amish community members only genetically isolated subpopulations (with frequent consanguineous marriages)
there is relatively high incidence of specific rare AR syndromes (e.g. Ellis-van Creveld s.) in some Amish communities, but not in others
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Factors disturbing Hardy-Weinberg equilibrium population is small
genetic drift founder effect Afrikaner subpopulation of South Africa:
in the middle of 17th century, 20 couples (mainly from Netherlands) settled there
explosive growth of population (population was genetically isolated from major population)
today, nearly 1 million of 2.5 million Afrikaners are descends of original 20 couples
1 early settler carried rare allele for variegate porphyria (AD disorder of late onset)
today's incidence of the disorder: South Africa: approx. 1/333 Netherlands: --- Finland: approx. 1/100 000
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Population studies in human
population studies are important part of human genetics there are medical data records about huge number
of people they are important for genetic counselling: they
provide allele frequencies for risk calculations, ... in human, population studies are also focused on genetic
structure of human subpopulations & the flow of genes among populations and between generations
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Genetic diversity in human populations
current studies suggest that human ancestors arose in Africa early humans spread out all over the world:
geographical isolation of small groups in new living conditions ( genetic isolation)
various selection factors in various regions genetic drift large human populations arose from small,
scattered original groups various new mutations in new regions
main ethnic groups evolved which include many other ethnic subgroups (they have their own characteristic sets of gene frequencies)
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Genetic diversity in human populations
medical importance: there can be huge differences among subpopulations sharing common area when considering e.g. genetic disorders, etc.
Population geneticsPopulation geneticsSexual reproduction and genetic structure of population Snmek slo 4Snmek slo 5Snmek slo 6Sexual reproduction and genetic structure of populationSexual reproduction and genetic structure of populationSexual reproduction and genetic structure of populationGenetic structure of populationGenetic structure of populationGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceHardy-Weinberg lawHardy-Weinberg law: Genotype frequenciesHardy-Weinberg lawHardy-Weinberg lawHardy-Weinberg lawH.-W. law: consequencesH.-W. law: consequencesSimplification of H.-W. lawH.-W. law: Gonosomal genes in populationH.-W. law: Gonosomal genes in populationH.-W. law: Gonosomal genes in populationHardy-Weinberg equilibriumSexual reproduction and genetic structure of populationEquilibrium in populationFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumPopulation studies in humanGenetic diversity in human populationsGenetic diversity in human populations