Chapter 7 - Population genetics

Bayesian analysis

- Consider the prior risk that individuals have a genetic variation, such as disease-causing variation - Take into conditional risk factors such as number of unaffected relatives - Provide a modified risk called the posterior risk

Exceptions to Constant Allele Frequencies

- Effect of mutation - Selection and fitness - Mutation and Selection Balance in Dominant Disease - Mutation and Selection Balance in X-Linked Recessive Mutations - Genetic drift, founder effect and gene flow.

Events that increase Genetic Drift

- Founding a new population - Bottlenecks (natural disaster, famine) - Geographic separation (being isolated by islands) - Cultural separation - Genetic drift is more remarkable in small populations.

Factors that affect frequencies of genetic variations in populations

- Nonrandom mating (random mating is also referred to as panmixia) - Natural selection (Balanced polymorphism) - Migration - Genetic drift (Population bottleneck & Founder effect) - Mutation

three major steps of Bayesian analysis

- Step 1. The prior probability is obtained from various possible circumstances. - Step 2. Additional information will then be used as the form of conditional probabilities. - Step 3. The posterior probability is then calculated.

Factors That Disturb Hardy-Weinberg Equilibrium

- Stratification - Assortative mating - Consanguinity

Exceptions to Large Populations with Random Mating

- Stratification: describes a population in which there are a number of subgroups that have—for a variety of historical, cultural, or religious reasons—remained relatively genetically separate during modern times. - Assortative mating: is the choice of a mate because the mating prefers certain particular traits - Consanguinity: like stratification and positive assortative mating, increasing in the frequency of autosomal recessive disease.

Hardy-Weinberg law relies on

- The population under study is large, and mating is random with respect to the locus in question. - Allele frequencies remain constant over time - no mutation - Individuals with all genotypes are equally capable of mating and passing on their genes; that is, there is no selection against any particular genotype - There has been no significant immigration of individuals from a population with allele frequencies very different from the endogenous population.

Phenotype frequency

- a fraction of individuals with a condition or trait in a population. - Phenotype frequencies are varied in different populations

How does fitness affect the mutant allele?

- f = 1 - mutant allele is just as likely as the normal allele to be represented in the next generation - f = 0 - an allele causes death or sterility, selection acts against it completely - f = 1-0 - transmission of the mutation, but at a rate that is less than that of individuals who do not carry the mutant allele.

Rule for Hardy-Weinberg formula

- p = allele frequency of the first (R) allele - q = allele frequency of a second (r) allele - The sum of the allele frequencies equals 1 - p2 and q2 are the genotype frequencies for each homozygote. - 2pq equals the genotype frequency of the heterozygote. The sum of all the genotype frequencies equals 1. - if a locus has three alleles, with frequencies p, q, and r, the genotypic distribution can be determined by ( p + q + r )^2 .

Balanced polymorphism (heterozygote advantage)

- results in the persistence of relatively high incidence of harmful recessive alleles in a large population. - Two or more forces (environmental threat vs. harmful allele) act in different directions on the alleles of a gene.

The Hardy-Weinberg principle ( equilibrium, law, or theorem)

- states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of disturbing factors - the frequency of the three genotypes AA, Aa, and aa is given by the terms of the binomial expansion of (p + q)^2 = p^2 + 2 pq + q^2 . - This law applies to all autosomal loci and the X-linked loci in females, but not to Xlinked loci in males who have only one X chromosome.

Genetic Drift

An evolutionary process in which gene frequencies change as a result of random fluctuations in the transmission of genes from one generation to the next. Drift is greater in smaller populations.

Bottleneck Effect

Another way of genetic drift is through a population bottleneck. That occurs when a large population is drastically reduced in its size, fewer traits are survived, and then when the population rebounds in size, the genetic variations are reduced.

X-linked Hardy Weinberg

Female: 3 genotype - p^2 + 2pq + q^2 Male: 2 genotype - p + q = 1

Example of Bayesian analysis

See more example on PPT

Posterior probability

The final probability for each event is known as its posterior or relative probability

Prior probability

The initial probability of each event that is based on ancestral or anterior information.

Conditional probability

The observations that modify these prior probabilities allow conditional probabilities to be determined.

Joint probability

The resulting probability for each event or outcome is known as its joint probability.

founder effect

When a small subpopulation breaks off from a larger population, if one of the original founders of a new group just happens to carry a relatively rare allele, that allele will have a far higher frequency than that in the large group it is derived from

Fitness

a measure of the number of affected offspring who survive to reproductive age, compared with an appropriate control group.

How can the Hardy-Weinberg equation be used?

can be used to predict genotype, allele, and phenotype frequencies.

What does population genetics deal with?

deals with genetic factors, such as mutation and reproduction, and environmental and societal factors, such as selection and migration. Together, these factors determine the frequency and distribution of alleles and genotypes in families and communities.

Second critical component of Hardy-Weinberg law

if allele frequencies do not change from generation to generation, the proportion of the genotypes will not change either; that is, the population genotype frequencies from generation to generation will remain constant, at equilibrium, if the allele frequencies p and q remain constant.

What kind of population does Hardy-Weinberg equilibrium occur in?

occurs in a large population in which there is random mating and a lack of migration, mutation, and natural selection, so that the allele frequencies remain constant.

Gene flow

occurs when populations exchange migrants who mate with one another. Through time, gene flow between populations tends to make them genetically more similar to each other.

Bayes' theorem

provides a very valuable method for determining the overall probability of an event or outcome, such as carrier status, by considering all initial possibilities (e.g., carrier or non-carrier) and then modifying or 'conditioning' these by incorporating information, such as test results or pedigree information, that indicates which is the more likely. Thus, the theorem combines the probability that an event will occur with the probability that it will not occur.

What kind of study is population genetics?

study of genetic variations in populations.

Tay-Sachs disease

the Tay-Sachs carrier frequency among Ashkenazi Jews is approximately 1 in 30 ( q 2 = 1/3600, q = 1/60, 2 pq = ≈1/30) as compared to a carrier frequency of approximately 1 in 300 in non-Ashkenazi individuals

Allele frequency

the fraction of an allele over all alleles in a population

Genotype frequency

the frequency of a particular homozygous or heterozygous genotype in a population.

Population genetics

the quantitative study of the distribution of genetic variation in populations and how the frequencies of genes and genotypes are maintained or altered over time both within and between populations.

First critical component of Hardy-Weinberg law

under certain ideal conditions, a simple relationship exists between allele frequencies and genotype frequencies in a population