Human Genetic Variation Flashcards
1
Q
SELECTION VIA RESEARCHERS/DEMOGRAPHICS OF HUMAN RESEARCH PPS
A
- contemporary ethic guidelines/research norms emphasise consent from pps = for collecting/storing/analysing personal data
- IV in planned comparisons
- DV in multivariate analysis/structural equation modelling/path analysis
- demographic info to check for subject selection/findings contextualisation/post-hoc comparison biases
2
Q
HUMAN PP CATEGORIES IN RESEARCH
A
- age/development/reproduction
- health/disability/addiction/physiological state
- sex/gender/orientation
- race/ethnicity
- occupation/work status/leadership
- socio-economic/immigrant status
- education/family
- political views/religion
3
Q
GENDER/SEX BINARY HISTORICALLY ALIGNED W/SEX CHROMOSOMES
A
- bio determinism based on binary (XX VS XY/egg VS sperm parent)
- challenged traditional binary view of sexual differentiation in humans as sole determinant of gender/sex
- sex chromosomes anomalies have various symptoms (ie. Klinefelter/Triple X syndrome (XXY/XXX); Turner syndrome (X whole/part missing)
- intersex = mild-severe development anomalies of sexual organs
- gender/sex = bio/social processes/factors = independent/influence each other in construction
- wide individual variation in traits not dimorphic as many dif experiences during development/social/physical/pre-birth physiological environmental factor (incl. hormones)
- gender identity/sexual orientation/behs NOT binary
4
Q
GENDER/SEX BINARY X INTELLIGENCE
A
- IQ tests devised >120ya repeatedly revised; high statistical reliability BUT limited validity; pps increase IQ scores w/test task training
- alternative theories = dynamic assessment testing proximal children development (Vygotsky/Feuerstein)/multiple IQ theory (Gardner/Sternberg)
- IQ studies select task range correlate scores to calculate g factor then correlated w/binary gender IV making inferences about bio processes in brain/genes
HYDE (2005) - gender similarity hypothesis = despite average bio difs, more similarities in brains/beh/psych traits between sex
5
Q
GENOME
A
genes -> all body/cell functions/reproduction & inheritance
6
Q
WHAT’S IN DNA?
A
- 2% genes = protein-coding DNA sequences
- 98% non-coding DNA = functionally important; contributes to complex genetic architectures in which genes embedded
7
Q
GENETRIC VARIATION IN SAME SPECIES INDIVIDUALS
A
DNA (GENOME) DIFS
- individual variation = between individuals
- within-pop variation = all individuals in pop/area that interbreed
- between-pop variation = between pop/areas that haven’t interbred in a while
ORIGINS OF GENOME VARIATION
- multiple variants (gene alleles/polymorphisms) occur in dif frequencies in-between pops
- DNA changes over time (mutations); recombined during reproduction
- migration/admixture between pops change alleles/polymorphism distribution in pop
8
Q
GENETIC VARIATION MEASUREMENT
A
- observation of traits/pedigrees (assumptions about genotype/inheritance)
- genetic/genomic measurements
NELSON et al (2013) - 19th century = Darwin’s evolution theory/Mendelian inheritance laws/biometry
- 20th century = quantitative genetics/biometry/molecular genetics emergence
- 1980-21st century = PCR test/genomics age
9
Q
LEVELS OF STUDYING GENETIC VARIATION
A
- biometry quantitative genetics measure observable traits (height/colouration/beh)
- genetics focused on difs between chromosomes/selected genes sequences
- genomics searches at many hundreds of loci or markers in genes/non-coding DNA (short sequences/non-coding DNA/single base-pairs)
10
Q
HUMAN GENOME PROJECT (1984-2004)
A
- international collaborative research aimed to completely map all human genes
- full sequence available 2001-2004 ($2.7b)
- genome info fully available; natural human sequences cannot be patented
- other initiatives focusing on genome diversity:
1. Human Genome Diversity Project (1990s)
2. HapMap Project (2003)
3. Genographic Project (National Geographic) (2005)
4. 1000 Genomes Project (2008)
11
Q
HUMAN BODY WEIGHT
A
- human body weight highly heritable BUT high polygenic trait
- studied +century; today studies reveal high complexity of genetic interactions/biologically relevant genes/non-coding DNA roles
- 100s of variants of many genes/non-coding DNA > 180 genomic loci determine how tall person grows in given environment
- locus = physical location of gene/DNA sequence on chromosome
12
Q
SHRINKING BODY HEIGHT MYSTERY
A
KOMLOS (1998)
- previously unknown cyclic human body changes in Europe/North America during Industrial Revolution
- shrinking soldier/worker body sizes despite growing economics
- labour sparked economic interest intensification in understanding bio causes/nutrition & health impact in early age on body conditions
13
Q
MEASURING HUMAN BODY
A
- anthropometry = measuring body/head (cranium)/face variations
- correlation w/racial/intelligence/beh (ie. criminal acts)/psych trait categories
GALTON (1888) - correlated head size VS degree results in 1000 male undergrads at Cambridge Uni claiming strong relationship/proposing later concept of generalised mental ability (GMA/g factor)
14
Q
BROAD POP SURVEYS/CASE STUDIES PRIOR TO GENOMIC AGE
A
- trace difs in mental/emotional/personality/beh traits (ie. alcoholism/feeblemindedness) vi IQ tests/genealogy/statistical surveys of mental/other illnesses (ie. Tuskegee syphilis stage in African-Americans)
15
Q
MODERN EUGENICS
A
- 1896; studying rich fam pedigrees; “superior IQ/abilities” = heritable
- racial segregation believed = necessary mechanism to maintain those in pop
- “defective” pedigrees study (socially deviant/problematic) widely accepted part of eugenic family studies
- pedigree imagery chart propelled broad misuse in professional sphere to gen popular culture
16
Q
DARWIN’S THEORY MISUSE
A
- original theory explains species diversity on Earth/how species w/dif adaptations appear/disappear
- misplaced morality/Social Darwinism = evolution IS NOT “survival of the fittest”
- selective (human-driven/artificial) breeding misconception as evolution
- natural selection DOES NOT optimise traits or results in progress/remove variation/prevent individuals reproducing/focus on goal-orientation
17
Q
SCIENTIFIC RACISM POST WW2
A
- deep societal impact
- crimes against humanity/genocide deploy simplified wrong claims about natural selection; argue bio “superiority” exists in particular groups/humans
- pseudoscience = seemingly objective justification for colonisation/slavery/social policies controlling/limiting life/opportunities/human rights considered “inferior”
18
Q
LONG-LASTING IMPACT OF EUGENICS/”RACE SCIENCE”
A
- eugenics/race science opposition amongst scientists/society disrupting theoretical claims/methodologies/definitions; generated disproving evidence
- opponent numbers/visibility amongst scientists started ^ post 1925 BUT eugenic ideas persisted widely socially (ie. included in 1950s high school textbooks)
- supremacy ideas persist to date; some scientists claim modern evidence/confirmation; necessary open debate
19
Q
INHERITANCE
A
- NOT simply blending egg/sperm parent characteristics
- modern genomics = most human trait variations are polygenic; Mendelian trait variations rare
- skin = largest organ; highly variable/complex:
1. not uniformly distributed
2. variation via bio sex; dif environment changes during disease/pregnancy
3. complex tangled relationship between genes determining polygenic inheritance; some have several alleles not always dominant-recessive
4. 15 genes regulating melanin amount in melanocytes of skin explain only some skin variation
20
Q
HIGHEST SKIN COLOUR VARIATION: AFRICA
A
- UV levels correlation suggests adaptive selective for lighter skin in high human latitude migration
- genetics studies in skin pigmentation mainly in European pops focussing on derived alleles strongly affected by lighter skin selection in low ultraviolet radiation (UVR) regions
- led to mistake of small gene number having large effect on skin pigmentation; skin colour variation research in Africans identified novel/canonical pigmentation genes
- spectrophotometry to determine melanin levels more accurately from upper underarm area (unexposed to sun); South African San have oldest genetic lineages in Africa; v light skin
21
Q
RACE
A
- biologically real BUT social/cultural construct; historically established social hierarchies/slavery
- modern genetics evinces that biologically distant human race concepts = obsolete
CANN (1998) - human genome diversity studies show large genetic variability due to difs among individuals in pops rather than difs between pops
YUDELL et al (2016) - genomic research shows using “race” in genetic diversity discussions = unnecessary (doesn’t add anything uncovered by pop cluster/dangerous (easily misleads laying dehumanisation groundwork)
22
Q
MIGRATION & ADMIXTURE
A
- 6 strangers w/same genetic ancestry
- genetic variation provides info about genetic relatedness between individuals/families OR which pop ancestors come from/if species interbred:
1. SNP mapping
2. mitochondrial DNA
3. Y-chromosome - construction of ancestry profiles gen evidence interactions between pops history NOT individual’s fam history
23
Q
MTDNA TESTS
A
- whole genome sequencing for individual is expensive (though getting cheaper w/technological advancement)
- mitochondrial (mtDNA) sequencing = cost-effective
- we share v similar mtDNA w/close relatives
- important genetic marker in forensics/anthropology/medicine/evolutionary research
BENEFITS - high number of copies in cell
- inherited from egg parent
- no recombination
- high mutation rate
24
Q
MTDNA HAPLOTYPE GEOGRAPHIC CLUSTERING
A
- oldest mtDNA haplogroups = Africa
- haplogroup L3 = ancestral to haplo-groups M/N which arose in North-East Africa; found in Europe/Asia
- haplogroups A/B/C/D frequent among Native Americans
- haplogroups A/B/C/D/F/G derived from M/N in Asia
- haplogroups H/I/J/N1b/T/U/V/W/X derived from haplogroup N in Europe
25
HOMO SAPIENS = MIGRATORY SPECIES
- human pops spatially connected/interacting
- no physiological reproductive barriers preventing admixture
- early/modern humans dispersed/migrated overcoming geographical isolation
- mixed diet/cog functions/cultural innovations enabled humans to survive in many dif environments & change them
26
EARLY/MODERN HUMAN MIGRATION
- out of Africa in big/small waves
- main migration/dispersal waves:
1. 300kya = migrations across Africa
2. 150-80kya = migration to Middle East/Eurasia
3. 60-40k = reached Australia
4. 20kya = reached Americas
27
PAUCITY OF STUDIES IN AFRICA
TANG & BARSH (2017)
- earliest modern humans in Africa 200kya; longest time to accumulate largest genetic diversity
- "signature/story book of human origins"
- overdue to focus/understand human diversity of Africa
28
CLIMATE MATTERS
SCERRI et al (2018)
- typical modern human features emerge in mosaic-like fashion in homo sapiens clade
- evidence that climate varied greatly; ^ aridity/humidity periods asynchronous across Africa
- genomic studies show early homo sapiens compromised several pops across Africa interlinked; w/connectivity changing through time prior/post main OOA (out of Africa) migration wave
29
HUMAN LOCAL ADAPTATIONS
FAN et al (2016)
- humans in geographical region = more frequent contact/admixture > distant pops
- several local adaptations found in some pops besides melanin concentrations in skin
- via continued migration; admixing spreads alleles across pops
30
INNER-ETHNIC FAMILY HISTORY
```
MIRANDA KAUFMANN (2017)
- black tudors; Africans known to live in Roman Britain
CABALLERO (2019)
- mixed fams in 1930s London/Liverpool = not rare sight
```
31
RACE = DISCRIMINATORY SOCIAL SEGREGATION MECHNISM
SIMS (2019)
- pseudoscientific bio concepts to cement social barriers after slavery abolition in 19th century; racial mixture considered medically pathological/unnatural
- problems of racialised social constructions/world views = segregation/race laws/racial discrimination/microlevel of interactions/symbolisms
- learning from past = collective ideas about physical attributes for individuals from dif races used to reinforce superiority concepts of some humans over others
32
POWER OF WORDS
BHOPAL (2004)
- first appearance of "race" in English language = 16th century w/expansion to colonisation via Europeans
- used to describe people in geographical regions (ie. European/Africans/Asians)/belonging to certain languages/religions (ie. Arab/Slavic/Jewish)
- race IS NOT subspecies
- ethnicity = people distinguished from others; used since Middle Ages
- BAME/BME = unclear; keeps focus on skin colour/imposed monolithic otherness label; many prefer self-identifying as BIPoC representing diverse cultural identities/shared systemic racism experience
33
WHO ARE WE?
- all present pops originate from 1 ancestral African pop
- genetic variation exists in every (human) species
- humans migrated/mixed continuously
- no biological basis for races
- race = social construct
34
GENETIC VARIATION & HEALTH
- genetic/epigenetic changes in dif environments/admixture in human pops explains susceptibility patterns to human pathologies
- health conditions can impact on capacity of individuals to respond to health threats that arise from quickly evolving microorganisms/viruses
- given expanded life span, aging processes have yet poorly understood impact on cognition/mental disorders can involve dif susceptibilities based on genetic signatures in individuals
- drive towards personalised medicine based on genetic profiling which possible due to modern technologies that are becoming cheaper/widely accessible
35
IMMUNOLOGICAL CHANGES IN HUMAN POP GENOMES
DE VRIS et al (1976)
- migration exposes human groups to new environments/diseases
- 60% mortality rates among Dutch colonists in Surinam from epidemics in yellow/typhoid fever
WALKER et al (2015)
- infectious diseases killed >10k individuals in 59 indigenous communities of Amazonia in past 200y BUT mortality rate/incidence decayed over time due to genetic adaptation
36
GWAS (Genome Wide Association Studies)
TAM et al (2019)
- complex analysis of SNP data identifies GWAS variants highly associated w/disease/disease risks
- ^ data amounts become available from hospitals
- genomic approaches can help to generate new diagnostic tools/drugs/therapies that prevent/treat diseases ^ effectively w/less side effects
37
GWAS BENEFITS
- relies on smallest possible DNA sequence changes (single nucleotides) frequent in pop (>1% termed SNP (single-nucleotid polymorphism); SNP in pp has C (nucleotide cytosin) instead of T (nucleotide thymin) in same sequence position; Ca 90% sequence variants in humans = SNPs
- looks at whole genome of many individuals; huge number/stable inheritance = good SNPs markers; associations w/polygenic traits ^ likely to be uncovered to understand variation/for applications
- SNPs in loci containing genes can be prioritised during analysis
38
GWAS LIMITS
- requires fully sequenced genomes of hundreds to thousands of individuals/their relatives (technological)
- w/thousands of loci included = ^ chance to detect more dif associations
- dark matter in genome; SNPs in non-coding DNA = no direct functional role/less important for polygenic trait; ^ difficult to interpret/confirm associations
39
GWAS IN PSYCHIATRY
HOWRITZ et al (2019)
- candidate genes studied for many decades BUT studies oft underpowered w/small samples
- first study funded by Wellcome Trust (2007)
- 2017 = 2,430 studies (1,818 phenotypes; 28,462 associated SNPs reported in GWAS catalogue); psych-related = 472 studies on 198 phenotypes/6,632 SNPs
40
SNP PHENOTYPE NETWORK
- red = STATSIG association w/psychological/psychiatric phenotypes + at least one other phenotype
- blue = non-psychological phenotype
41
NEW ETHICAL CHALLENGES FOR APPLICATIONS
FAN et al (2016)
- chance for bias in sampling rules of pop/individual categorisation
- expanded precision/tools for genetic interference
ETHICS/MORALITY
- which pop parts represented in studies?
- which traits = healthy/normal?
- prediction errors = who is carrier/affected by predicted risk under which life/environment conditions?
- how/when/where is most detailed genetic fingerprint of individual used?
42
"WEIRD" PSYCHOLOGY
```
W = Western
E = Educated
I = Industrialised
R = Rich
D = Democratic
```
43
WHY DECOLONISE PSYCHOLOGY?
1. Inability to create world view understanding of human beh.
2. Minority groups cannot identify.
3. Can lead to discrimination.
4. Globalised world = globalised education.
CRITICAL QUESTIONS
- eurocentric views
- cross-cultural western theory application
- number of citations/first or last authorship conducted/taught research; staff involved in research/education/professional training
44
WHAT CAN WE DO?
GENERAL
- Indigenisation/Normalising Non-WEIRD Experiences = drawing on local knowledge to modify standard practice
- accompaniment = share expertise globally
- denaturalising conventional scientific wisdom = drawing on local knowledge of marginalised communities
SPECIFIC
- changing reading lists/references/citations
- teaching about bias
- learning/teaching about history if female/BAME psychology
45
SUMMARY I
- human pps categorisation = important tool in psychological research/applications; requires careful consideration/justification to avoid bias
- timely to reconsider sex/gender binary; generate new conceptual frameworks in human research
- despite bio difs/need to understand gender difs, big gender similarities is psych/beh traits evident
- genetic variation estimated (observable physical traits/pedigrees/heritability estimates distribution)/defined at chromosomes level (ie. sex/gender binary)/genome (DNA nucleotid sequences)
- economic/societal interest on advancing natural sciences/healthy workforce need/colonial societal superiority concepts/19th century inequality foster racial pseudoscience/eugenics rise
- continued need to learn/remember lessons from past about severe impact/dire consequences of half century eugenics in science/society; Widespread Eugenics policies ie. racial segregation/forced sterilisation to breed "perfect" humans/society formally denounced post WW2 BUT ideas still circulate; returning pseudoscientific "race science" claims debunked/negative LT societal impact
46
SUMMARY II
- race ISN'T biological but social construct; skin colour trait underpinned by complex genetic architecture interacting w/environment; recent genomics advances/studying African skin colour diversity revealed genetic mechanism/adaptations/pop structure insights
- mitochondrial DNA/SNPs variation allow human ancestry reconstruction plus to extends relatedness over past generations
- humans = migratory; admixtures traced back thousands years in DNA; historical records evince recent admixtures in pops connected via trade/migration/colonisation/other contacts; some genetic variance arises from local adaptations to environmental conditions/diseases
- important to apply scientific terminology correctly in wider society communication about gen knowledge
- GWAS analyse whole genomes of people in same/dif pops; offers new opportunities to discover mechanisms/measure inheritance/ancestry/predict risks for personalised psychiatry/psych therapies
- WEIRD oversampling might limit/skew our human beh understanding
