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The Major Histocompatibility Complex on chromosome 6 encodes a diverse array of genes involved in the immune and inflammatory response. The region is remarkably polymorphic and has been associated with susceptibility to autoimmune and infectious disease. The approaches to defining and understanding the nature and consequences of genetic diversity in the MHC are reviewed in terms of the biology of encoded molecules, evolutionary selective pressures and relationship to disease. Progress in haplotypic analysis of the MHC, resequencing and fine mapping are discussed together with insights from structural biology and detailed functional characterisation of the consequences of genetic diversity. The role of genetic variation in the MHC for a number of specific diseases are reviewed including rheumatoid arthritis, haemochromatosis, type 1 diabetes, coeliac disease, narcolepsy and sarcoidosis with emphasis on progress in defining the functional basis of disease associations, for example modulation of alternative splicing by genetic variation associated with sarcoidosis.

For ongoing coevolution of the grass-endophyte symbiosis through the agents of natural selection, there must be genetic variation within populations for both host and endophyte. The breeding systems of both symbiotic partners influence the distribution and level of genetic variation within populations. Traditional reaction norms and symbiotic interaction norms can be useful in depicting host genotype interactions with environment and infection. Examples are provided for both agronomic and native grass-endophyte symbioses. Endophytes can also modulate phenotypic plasticity of their grass hosts in relation to environmental variation. There is evidence that endophyte genotypes (haplotypes) can differ significantly in their impact on host growth and physiology. Genetic diversity of endophyte isolates has been quantified using isozymes and DNA markers. Host-endophyte compatibility can vary among endophytes and their host grasses as revealed by reciprocal inoculation experiments using fungal isolates from different host populations or species. Multistrain infections of single grass hosts and fungal hybridization within individual hosts have been determined for some symbioses. Genetic variation in both host and endophyte will expedite the continued coevolution of the symbiosis.

The extent of single nucleotide polymorphism is reviewed, together with insights gained into the nature of allelic architecture in terms of haplotypes, linkage disequilibrium and recombination. The utility of SNPs in defining genetic determinants of common disease is discussed including the rationale, results and diverse applications of the International HapMap Project. The recent development and application of genome-wide association studies is reviewed including the Wellcome Trust Case Control Consortium study of seven common diseases. Issues relating to design, analysis and interpretation of such studies are described. A detailed review of age-related macular degeneration and inflammatory bowel disease is presented, two common multifactorial diseases where genome-wide association studies have recently enjoyed considerable success. Research in these diseases illustrates the timeline of different approaches used in defining genetic determinants of common disease and how such analyses can provide novel insights into disease pathogenesis.

Genetic diversity observed in human populations provides unique insights into the selective pressures which have shaped our recent evolutionary past. Evidence to support this view is described in this chapter including concepts of genetic hitchhiking and selective sweeps, together with signatures of selection found from analysis of genetic variation. Insights gained from sequencing the chimpanzee and rhesus macaque genomes into human genetic diversity and selection is described. Evidence for selection from genetic studies of lactase persistence is reviewed for European, African, and Middle Eastern populations. The complex genetics of skin pigmentation is discussed, including the role of model organisms in identification of a human gene (SLC24A5) within which nucleotide diversity plays a major role in determining the light skinned pigmentation phenotype observed among Europeans. The chapter concludes with discussion of genome wide analyses using high density SNP panels in which many new loci showing evidence of selection are being identified.

This chapter reviews the most common measures of genetic variation used in conservation genetic studies. These include percentage of polymorphic loci, alleles per locus/allelic richness, expected heterozygosity, dominant neutral markers, nucleotide diversity, haplotype diversity, non-neutral markers and neutrality tests, and quantitative additive gene variation.

This chapter presents the representations of diabetes as a racialized disease with the ideologies of research participation and humanitarian service found within the sampling apparatuses along the border. It is shown that a transnational protogenetic subject is crafted through the biological embodiment of Mexicana/o ethnicity as an admixed biological group. The chapter also explains the admixture–susceptibility matrix, and offers its resonance with contemporary and historical nativist impulses. The diabetes susceptibility haplotype transforms the conventional epidemiological concern for predicting which persons will become ill to predicting who is an ill person. The chapter demonstrates that while the ideology of diabetes science may interpellate Mexicanas/os into state subjects, it does so by naturalizing a particular social order. Locating diabetes within Mexicana/o ethnoracial admixture cleaves both Mexicanness and the illness called diabetes from the social histories that produced the ethnic label and the socially embodied conditions which contribute to the disease.

This chapter introduces the theme of bottom-up agency with an account of struggles for authority between socially and scientifically constituted groups of genetic research subjects. It addresses how subsequent human genome variation research projects continue to bypass responsibility for their roles in co-constituting natural and moral orderings of human difference. It considers the assumptions about the constitution and proper ordering of human differences and demonstrates how they hindered consideration of the role that both population genetics and liberal systems of rights play in producing human differences. This chapter shows that the Human Genome Diversity Project and Haplotype Map Project (HapMap) cases suggest that genome scientists and their administrators seek “precise” methods for ordering human differences and defining groups that they believe protect against bias, namely racism.

Who in the world could and should properly represent variation in the human genome? American genome scientists and policy makers argued that previous global efforts to represent the variability of human genomes failed because they sought DNA from so-called “vulnerable” indigenous populations. They proposed instead to collect from majority populations, populations they believed possessed the power to represent themselves. Based on fieldwork and interviews with the main architects of the International Haplotype Map Project, the chapter brings to light the failure of this liberal democratic imaginary to respond to the on-the-ground reality that there were no clear well-bounded majority populations who could represent themselves independent of efforts to engage them. Far from addressing concerns about exclusion and discrimination, these efforts raised questions about how to constitute groups with both political standing and epistemological value. These questions of representation in turn raised questions about how to justly allocate resources in a world where genomics had opened up new narratives of truth, justice and the human condition.

The allelic evolutionary genetic models explored so far are applicable to genetic markers. However, DNA sequences harbor a lot of information about the evolutionary past that would be missed if different sequences were simply treated as different alleles. This chapter introduces some important methods and concepts applicable to the analysis of DNA-sequence data. The null models for analyzing sequence data are derived from the neutral theory of molecular evolution. Historically, however, the neutral theory has made a large impact on evolutionary genetics. Therefore, this chapter starts by reviewing its important contribution. Then, important parameters and statistics for analyzing sequence variation are introduced, including a plethora of neutrality tests. The chapter ends with a cautious focus on the powerful tool of genome scan analysis and its utility for identifying regions of the genomes potentially under selection. This includes a section on more recently derived statistics which incorporate information on haplotype structure.

Different types and phases of a selective sweep (hard, soft, partial, polygenic) generate different patterns of departures from neutrality, and hence require different tests. It is thus not surprising that a large number of tests have been proposed that use sequence information to detect ongoing, or very-recently completed, episodes of selection. This chapter critically reviews over 50 such tests, which use information on allele-frequency change, linkage disequilibrium patterns, spatial allele-frequency patterns, site-frequency spectrum data, allele-frequency spectrum data, and haplotype structure. This chapter discusses the domain of applicability for each test, and their strengths and weaknesses. Finally, this chapter examines application of these methods in the search for recent, or ongoing, selection in humans and for genes involved in the domestication process in plants and animals.