Learning objectives
The aim of the course is to provide the graduate with an advanced knowledge in the field of population genetics, knowledge that can be useful in topics such as estimation of the genetic diversity and conservation of populations belonging to threatened or endangered species. The ability to understand is stimulated by a close interaction between teacher and learner in the analysis of a problem (in knowing how to clearly formulate a question), in the choice of the most appropriate method of analysis, and in the evaluation of the results. Particular attention is paid to a detailed description of seminal scientific studies, accompanied by an update to more advanced studies through the search for papers in MEDLINE database. The course relies on two reference texts, respectively on genetics of human populations and conservation genetics. At the same time, the course is a continuous stimulus to deepen the topics treated, through a constant reference to the advanced literature and to the methods. The detailed mathematical description of the multivariate statistical methods presented in the course aims to make the student understand that statistics, a fundamental element in population genetics, is first of all a choice of path, the most suitable rational path for the analysis of the collected data.
Prerequisites
Good knowledge of genetics, mathemarics and statistics
Course unit content
The course of Population Genetics (6 cfu) explains the origin and meaning of the law of Hardy-Weinberg, which is the basis of matter. Once some deviations from the Hardy-Weinberg equilibrium have been highlighted, the course describes in great detail the effects operated by the main evolutionary agents, both individually and cooperatively, in the change of the allele frequencies during evolution. The evolutionary agents examined are the following: mutation, natural selection, gene flow, genetic drift, and inbreeding. Particular attention is paid not only to human populations, for which extensive literature is available, but also to animal populations. In particular, to animal populations belonging to threatened or endangered species. A relevant part of the course, indeed, includes conservation genetics. It includes the evolutionary genetics of natural populations, an estimate of the genetic diversity in endangered species, the effects of a small population size on the genetic variability, the relationship between genetics and extinction, resolution of taxonomic ambiguities with genetic analysis, and the use of genetic techniques in forensic matters related to the protection of endangered species. The course is enriched by an accurate mathematical description of the following multivariate statistical methods: linear and quadratic discriminant analysis, principal component analysis, correspondence analysis, multiple linear regression and canonical correlation. The description of each method is accompanied by a number of case studies taken from scientific literature and concerning both population genetics and conservation genetics.
Full programme
Origin of the Hardy-Weinberg law and related assumptions.
Calculation of the allele frequencies in human populations for autosomal and sex-linked genes. Statistical validation of the Hardy-Weinberg equilibrium.
Linkage disequilibrium
Deviation from the Hardy-Weinberg equilibrium at locus MHC (genes HLA-1 and HLA-2)
Estimation of the genetic diversity between populations and within populations (Wright's fixation index).
Apportionment of the genetic variance in human populations into the main components from analyses based on classical and molecular genetic markers.
Allele delta-32 allele at locus CCR5 (cytokine receptor gene) and resistance to HIV-1 infection. World-wide distribution of allele delta-32; estimation of its age using the coalescence theory and data from analysis of ancient DNA; prediction of the selective agent responsible for the high frequency of allele delta-32 in Europe and Middle East
Allele delta-508 allele at locus cystic fibrosis. Selective advantage for the heterozygote genotype against infection by Salmonella typhi.
The concept of integrated judgment in multivariate statistics: the linear discriminant analysis by Ronald Fisher (detailed mathematical description of the method).
Linear discriminant analysis in the identification of carriers of deleterious recessive alleles (e.g. allele sickle cell anemia allele at locus beta-globin). Application of the linear discriminant function to a census problem concerning the protected species Caprimulgus europhaeus.
Mahalanobis’s generalized distance and quadratic discriminant function.
Equilibrium between selection against the genotype recessive homozygote genotype and selection favoring the heterozygote genotype at locus beta globin. Study of an African population (Yoruba of Nigeria). Cultural change and evolution of hemoglobin S.
Multivariate statistics: principal component analysis (PCA) by Harold Hotelling (description of the main steps of calculation of the method).
PCA analysis of the genetic relationships between 38 world-wide human indigenous populations. Implications with the origin and ancient migrations of Homo sapiens.
PCA analysis in the construction of genetic landscapes: genetic history of Italy from classical and molecular markers. PCA analysis and the Neolithic transition in Europe. Comparison between the reconstruction predicted by classical genetic markers and that predicted by ancient DNA. Evidence for natural selection in human populations from PCA of genomic data.
Genetic distance between populations and the construction of phylogenetic trees.
Molecular clock and evolution of Primates. From the seminal work by Sarich and Wilson (Science, 1967) to the most recent studies (molecular clock and evolution of Metazoan).
Relationship between microevolution (change of allele frequencies) and macroevolution (incipient process of sympatric speciation) in the parasitic insect Rhagoletis pomonella.
Multivariate statistics: correspondence analysis (CA) by Jean-Paul Benzécri (description of the main steps of calculation of the method). Application of CA in the genetic analysis of populations of cattle breeds, for conservation purposes.
ID: Knowledge and understanding
ID: Autonomy of judgment
ID: Ability to learn
Inbreeding. Calculation of the inbreeding coefficient and application in human pedigrees and populations. Relationship between natural selection and inbreeding.
Inbreeding and inbreeding depression in mammals. Loss of deleterious alleles by purifying selection: the case of Elaphurus davidianus (Père David's deer).
The method of “lethal equivalents” to estimate the inbreeding depression in animal populations.
Relationship between inbreeding and extinction. Direct evidence for extinction due to inbreeding and loss of genetic diversity, from scheduled crossings in laboratory and studies on natural population.
Measure of the genetic diversity: proportion of polymorphic loci, mean heterozygosity and allelic diversity.
DNA microsatellite DNA: a fine, selectively neutral marker of genetic diversity in populations.
Reduced genetic diversity in threatened species: the case of the Australian wallaby, Petrogale lateralis.
Use of mitochondrial DNA for conservation purpose of protected species. Detection of illegal hunting and food fraud (DNA forensics).
ID: Knowledge and understanding
ID: Autonomy of judgment
ID: Ability to learn
Examination of the evolutionary agents causing a change of the allele frequencies. First evolutionary agent examined: the mutation. Number of new mutant alleles in one generation. Fate of mutant alleles. Equilibrium between mutation and natural selection.
The genetic load in populations. The recessive allele chondrodystrophy in the condor of California (Gymnogips californianus). Management options for chondrodystrophy in a population of Gymnogips californianus.
Examination of the evolutionary agents causing a change of the allelic frequencies. Second evolutionary agent examined: the genetic drift.
Genetic drift in laboratory populations of Drosophila melanogaster. Genetic drift in human populations: the case of allele achromatopsia (color blindness) in the island of Pingelap.
Computer modeling of genetic drift by simulation tests. Effect of population size. Effective population size (Wright's formula). Genetic drift in populations of the parasitic insect Tribolium castaneum.
Effects of bottleneck (sharp reduction in the size of a population) in Drosophila melanogaster, from analysis of a number of DNA microsatellite loci. Bottleneck in the Mauritius kestrel population (Falco punctatus) and related loss of genetic diversity. Inbreeding depression in a small and isolated population: the case of the gray wolf on Isle Royale. Genetic rescue of a population of Vipera berus close to extinction. Equilibrium between mutation and genetic drift.
Examination of the evolutionary agents causing a change of the allele frequencies. Third evolutionary agent examined: the natural selection.
Natural selection at locus ACE (acetyl-cholinesterase) in Anopheles populations. Effects of selection at locus LCT (persistence of the activity of lactase in adulthood) and evolution of the diet in human populations. Duffy blood group and malaria in African populations. Effects of selection in populations living at high altitude (Andes and Tibet).
Simulation of natural selection. Absolute and relative fitness. Selection against the recessive homozygote. Selection against the dominant allele. Selection against the heterozygote. Selection favoring the heterozygote. Balancing selection and malaria in African populations. Natural selection in Biston betularia (the industrial melanism described by a change in allelic frequencies).
Selection and mutation. Selection against a mutation. Selection and genetic drift. Natural selection on quantitative poly-genic traits: directional selection, stabilizing selection and destructive selection. Effects of selection on the evolution of skin pigmentation in human populations.
ID: Knowledge and understanding
ID: Autonomy of judgment
ID: Ability to learn
Examination of the evolutionary agents involved in the change of allelic frequencies. Fourth evolutionary agent examined: the migration, or the gene flow.
Simulation test of gene flow between populations: unidirectional and bidirectional model. Structured migration by clan. Altitude and population structure in Jujuy (Argentina). Estimation of gene flow from migration matrix. Gene flow between archaic man (Neanderthal) and modern man.
Reduction of gene flow in natural populations due to fragmentation. Impact of habitat fragmentation on the metapopulation of the endangered Northern Woodpecker (Picoides borealis).
Resolution of taxonomic ambiguities and definition of management units. Resolution of taxonomic ambiguities from genetic data. Outbreeding depression. Estimation of the introgression from dog to the endangered species Ethiopian wolf using DNA microsatellite loci.
Multivariate statistics: multiple linear regression (detailed mathematical description of the method).
A study, based on multiple linear regression, to estimate the genetic diversity in overfished populations.
Multivariate statistics: canonical correlation (correlation between two sets or canons of variables) (description of the main steps of calculation of the method).
A canonical correlation study between two sets of variables: a set on the quality of air and a set on the quality of health.
A study of conservation genetics in Italy: extinction, hybridization and overpopulation: genetic data and management of wild boar (Sus scrofa) in Italy.
ID: Knowledge and understanding
ID: Autonomy of judgment
ID: Ability to learn
Bibliography
Relethford, J.H. Genetica delle popolazioni umane. Casa Editrice Ambrosiana
Frankham R., Ballou J.D., Briscole D.A. Fondamenti di genetica della conservazione. Zanichelli
Further didactic material is available at the platform Elly.
Teaching methods
Frontal lessons
Assessment methods and criteria
The method of learning assessment is an oral exam with discussion lasting 45 minutes. The student is asked to express with a good property of the language a topic of population genetics, a topic of conservation genetics, and to describe the mathematical steps of a multivariate statistical method with related applications. The student is given the opportunity to freely choose a scientific article and to present it with the utmost accuracy.
Other information
A good knowledge of the English language is appreciated.
