Human Genetic Variation and Genomics

Human Genetic Variation

Recording and Measuring Individual Variation
  • Lecture focuses on how individual variations are recorded and measured in study subjects.
  • Explores the history, controversies, and societal impact of human genetics research.
  • Discusses how genetic variation is measured and emphasizes the importance of understanding modern genetic concepts for psychology, health, and life sciences research.
  • Highlights the warning that careless use of genetic concepts can lead to detrimental outcomes, referencing Weiss & Lambert (2011).
Categories and Binaries in Research
  • Discusses the use of categories and binaries in selecting human participants and recording their demographics for research.
  • Categories include:
    • Age, developmental stage, reproductive stage
    • Health, ability, addiction, physiological state
    • Sex/gender, sexual orientation
    • Race, ethnicity
    • Occupation, work status, leadership
    • Socio-economic status, immigration status
    • Education, family
    • Political views, religion
  • Highlights the distinction between biological and non-biological factors in research and the influence of individual experiences and beliefs.
Reproductive Binary and Sex Chromosomes
  • The reproductive binary (XX and XY chromosomes) defines sex at birth, determining egg/sperm parent and male/female categories.
  • Sex chromosome anomalies include:
    • Klinefelter syndrome (XXY): Individuals with XXY chromosomes.
    • Triple X syndrome (XXX): Individuals with XXX chromosomes.
    • Turner syndrome: Individuals with missing X chromosomes (whole or part).
  • Intersex individuals exhibit mild to severe anomalies in the development of sexual organs in newborns but have intact sex chromosomes.
  • Environmental factors significantly shape gender identity, sexual preferences, and behaviors, which are not captured by the reproductive binary.
  • Traditionally, a deterministic view of sexual differentiation aligns with the reproductive binary, potentially causing challenges and bias in research.
  • Gender/sex reflects that biological and social processes are interdependent and influence gender identity construction (e.g., Morgenroth & Ryan 2021).
Intelligence Quotient (IQ) and Reproductive Binary
  • IQ tests, revised repeatedly over 120 years, have high statistical reliability but limited validity; scores can increase with training.
  • Alternative theories include dynamic assessment testing proximal development (Vygotsky, Feuerstein) and multiple intelligence theory (Gardner, Sternberg).
  • IQ studies correlate scores with reproductive binary (sex) as an independent variable (IV), inferring biological mechanisms underpin cognition and brain function.
  • Meta-analyses indicate that environment, parent education, and school type explain most variance in attainment between school-aged girls and boys (Hyde & Linn 2006).
  • Gender similarity hypothesis (Hyde 2005): Brains, psychological traits, and behavior are very similar between women and men despite biological differences.
Influence of Research Norms and Biases
  • Research is influenced by norms and biases.
  • Categories of participants:
    • Independent variable (IV) in planned comparisons
    • Dependent variable (DV) in multivariate analysis, structural equation modeling, path analysis
    • Demographic information to check for biases and contextualize findings
  • Contemporary ethics guidelines require consent for collecting, storing, sharing, and analyzing personal data.
The WEIRD Problem in Psychology
  • Critique focuses on the over-reliance on Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations in psychology research.
  • Raises concerns about the representativeness of mainstream psychology and the underrepresentation of BAME (Black, Asian, and minority ethnic) individuals and female subjects.
  • Subcultural areas are not adequately represented, leading to:
    • Inability to create a world-view understanding of human behavior
    • Minority groups not identifying with research findings
    • Potential for discrimination
    • Challenges in a globalized world with globalized education
  • Critical questions:
    • Eurocentric views in research questions and funding
    • Application of Western theories cross-culturally
    • Diversity and representation in research citations and authorship
    • Tradition and innovation in educational and training curricula (e.g., disability, health)
Culture Matters
  • The lecture emphasizes the importance of culture in various contexts, referencing examples from news articles and studies.
  • Examples include:
    • Progressive views in media such as 'Star Trek: Discovery'
    • Greta Thunberg's advocacy for climate experts
    • Schools becoming more eco-friendly
    • Removal of a Black Lives Matter sculpture
    • Ethical issues in using AI for grading
    • The Nobel Prize in Chemistry 2020
    • Ethical considerations in AI healthcare applications
Historical Context and Eugenics
  • Highlights the historical context of genetics research, including the influence of the industrial revolution and eugenics.
  • Discusses the mystery of shrinking body heights during the industrial revolution and economic incentives for researching height variations.
  • Explores quantitative genetics and anthropometry, including correlations between body measurements and racial categories.
  • Discusses Francis Galton’s work on head size and intelligence, noting the low correlation found by Pearson.
  • Examines the heritability of human behavior, the misuse of pedigrees, and the coining of the term eugenics by Francis Galton.
  • Discusses misconceptions and politicization of Darwin’s theory of evolution, including misplaced morality and Social Darwinism.
  • Addresses the history of eugenics and scientific racism, including crimes against humanity and genocide, exacerbated by colonial policies and racist attitudes, such as the Bengal famine of 1943 and Nazi concentration camps.
  • Highlights the long-lasting impact of eugenics and race science, noting early opposition but persistent ideas, and the necessity of learning from history.
  • Eugenics Record Office archives room.
Genetic Concepts and Genome
  • Genes account for only 2% of the genome; non-coding DNA makes up 98% and contributes functionally to genetic architectures.
  • Explains gene architectures, polymorphisms, mutations, and gene-environment interactions.
  • The nature-nurture debate is considered a conceptually deficient dichotomy, and the activity of a gene cannot be separated from its environment.
  • The genome comprises all DNA present in each cell of the body.
Measuring Genetic Variation
  • Biometry and quantitative genetics measure observable traits.
  • DNA contains 4 bases (A, C, G, T) that pair as A&C and G&T.
  • Genomics searches all DNA for markers at genetic loci, including genes and non-coding DNA.
  • Genomic sequences are now cheap to extract but complex to analyze, requiring bioinformatics.
Causes of Genetic Variation
  • Tiny genetic variations between individuals arise from:
    • Spontaneous DNA changes (mutations)
    • Different environmental conditions
    • DNA recombination during egg and sperm production
  • Variation within and between populations is due to:
    • Multiple variants (gene alleles, polymorphisms)
    • Genetic admixture between populations
Human Genome Project (HGP)
  • An international, collaborative research project that aimed to completely map all human genes.
  • The full sequence became available in 2001-2004, costing 2.72.7 billion.
  • Established Bermuda Principles for making genome sequences publicly available within 24 hours.
  • Ethical concerns include the need to benefit indigenous populations.
  • Examples of initiatives focusing on genome diversity: Silent Genomes Project (Canada), Aotearoa Variome Project (New Zealand), Human Genome Diversity Project, HapMap Project, Genographic Project, 1000 Genomes Project, and The Cancer Genome Atlas (TCGA).
  • Natural human sequences cannot be patented
Race as a Social Construct
  • Concepts of biologically distinct human races are obsolete.
  • Using the term 'race' in relation to human genetic variation is unnecessary and dangerous.
  • Race constructs were historically used to establish social hierarchies and slavery.
  • Most genetic variability is due to differences among individuals within populations.
Social Segregation
  • The term “race” appeared in the late 16th century during European colonization.
  • Pseudoscientific concepts cemented social barriers after slavery abolition.
  • After WW2, “ethnicity” was used to distinguish “others.”
Skin Pigmentation
  • Correlation with UV levels suggests adaptive selection for lighter skin at high latitudes.
  • Skin pigmentation genetics focus on derived alleles for lighter skin.
  • Research reveals very lightly pigmented skin in the San of South Africa.
Modern Genomics
  • Modern genomics shows human trait variations are polygenic.
  • Skin is the largest organ with highly variable color.
  • Complex relationships exist between genes determining polygenic inheritance.
  • 15 genes regulating melanin explain only some skin color variations.
  • Skin color varies across the body and changes with sex, environment, disease, or pregnancy.
Human Migration
  • Early modern humans in Africa 200,000 years ago accumulated genetic diversity.
  • Research of skin color variation in Africans has identified novel and canonical pigmentation genes.
  • Main migration and dispersal waves:
    • 300,000 years ago: migrations across Africa
    • 150-80,000 years ago: to Middle East & Eurasia
    • 60-40,000 years ago: reached Australia
    • 20,000 years ago: reached the Americas
Ancestry and Genetics
  • Each individual shares genetic ancestry with many strangers.
  • Genetic ancestry is a long story of human migration and admixtures.
  • Population ancestors interbred with other human species.
  • A multidimensional view of ancestry is necessary.
    • Mitochondrial DNA
    • Y-chromosome DNA
    • Whole-genome (SNP mapping)
Genetic Adaptations
  • Local adaptations occur in isolated regions.
  • Genome change can be driven by selection.
  • Subsequent migration and admixture can spread DNA variations.
Human Genetic Variation
  • Understanding genetic variation is important for health and aging.
  • Migration exposes humans to new diseases and parasites.
  • A genetic bottleneck limits genetic variation.
  • Understanding genetic variation and epigenetic processes can help to explain susceptibility to pathologies and identify health and environmental risks.
Genome-Wide Association Studies (GWAS)
  • Ethical challenges in research and application:
    • Population representation in studies
    • Defining healthy traits
    • Prediction errors
    • Risks of misuse of genetic “fingerprints”
GWAS Benefits and Limitations
  • Benefits:
    • Relies on SNPs
    • Looks at the whole genome
    • Associations with polygenic traits
    • SNPs in loci connected to genes
  • Limitations:
    • Requires sequenced genomes
    • Higher chance to detect many associations
    • SNPs in non-coding DNA
Summary
  • Careful participant categorization is crucial for psychological research to avoid bias.
  • Timely reconsideration of the sex/gender binary is needed in research.
  • There are large similarities in psychological and behavioral traits despite biological differences.
  • Genetic variation can be estimated at chromosome or genome levels.
  • Historical economic and societal interest fostered racial pseudoscience and eugenics.
  • Lessons from the past about eugenics' severe impact must be remembered.
  • Race is a social, not biological, construct.
  • Skin coloration is a trait under complex genetic and environmental interaction.
  • Advances in genomics reveal insights into genetic mechanisms and population structures.
  • GWAS offers opportunities for personalized therapies.
  • Oversampling of WEIRD limits understanding of human behavior.
  • Decolonizing Psychology is a necessary effort.
  • Correct terminology is essential for societal communication about generated knowledge.