Development of the embryo

• fertilized egg - single cell

• hoe does the information in the DNA generate a complex structure

• gestation period (happens early in the developmental cycle)

  • humans = 266 days

  • mice = 20 days

  • elephants = 645 days

Later development of the embryo includes:

• neurulation

  • formulation of spinal cord and brain (occurs after gastrulation)

• organogenesis

  • formation of organs

Developmental problems when the neutral tube fails to close

• spina bifida

Organogenesis

e.g. the mammalian forelimb

• cells are directed to specialise in different ways

• controlled by genes being switched on and off in different ways in different cells

• epigenetics

Epigenetics

• Professor Conrad Hal Waddington (1905-1975)

  • proposed the term in 1940

• Professor Sir Adrian Bird (1977- )

  • discovered the molecular basis of epigenetics

• genetic changes not associated with changes in the DNA sequence

• genes permanently switched on/off

• determines cell type

  

Genes involved in development

• how do we know which genes are involved in controlling development

• make use of mutants

• drosophila (the fruit fly)

• Homeotic mutants

• mutants that affect development

• genes which have a universal function in development

• HOX genes

• e.g. eyeless mutant of drosophila

Eyeless mutant

• caused by a mutation in the Pax-6 gene

Human homologue of Pax-6

• mutation in the Pax-6 gene causes bilateral Anopthalmia

Genetics versus the environment

• nature - nurture debate

• clear genetic influences

  • e.g. haemophilia: presence of the defective alleles causes the phenotype

• clear environment influences

  • e.g. ricketts: vitamin D deficiency causes phenotype

• genetic and environmental influences

  • rhesus blood group and pregnancy

  • blood groups Rh+ and Rh-

    

Genetics versus the environment

• e.g. temperature sensitive genes

• siamese cat

  • growth in a cooler environment produces a darker colour in extremities - the pigmentation gene is “switched on“ in a cooler environment

• himalayan rabbit and guinea pig

measuring the effects of genetics versus the environment

• keep the environment constant

  • e.g. plant genetics

• keep the genetics constant (more difficult)

• need for genetically identical individuals

  • inbred lines (e.g. laboratory mice)

  • cloning (e.g. “dolly“ the sheep)

  • twins

Studies on twins

Heritability

• probability that shared phenotypes are NOT explained by the environment or by chance

• gives an approximation of the contribution of genetics to a phenotype

  • e.g. a heritability score of 80% means that there is probably a significant genetic effect

• can be determined by comparing phenotypes in monozygotic (MZ) and dizygotic (DZ) twins

Case study: genetics of schizophrenia

• specific clinically defined category of neurodiversity

• long-term condition that involves psychosis

• difficulty in distinguishing own thoughts from reality

  • long term debate about whether this is genetically inherited (nature) or induced by the environment (nurture)

• historically (up to 1970s) - thought to be related to upbringing of children

• early studies 1950s - 1970s identified that it ran in families

  • a possible genetic influence?

• twin studies demonstrated a high degree of heritability

• concept of “genetic susceptibility“

• other factors affect it, but only individuals that are genetically susceptible

• 2017 Danish twin study (Hilker et al 2017)

• Danish twin register - started in 1954 and includes twins born from 1970 onwards

• complete records for all Danish-born twins born from 1968

• Danish Psychiatric Central Research Register - all psychiatric admissions since 1969

• 31,524 twin pairs

2017 Danish twins study

• estimated the heritability as 79%

• major genetic component

Other factors involved

• upbringing but only if genetically susceptible

• more schizophrenic individuals born in winter rather than summer- linked to influenza epidemics

• infectious agents- the parasite toxoplasma gondii

• development errors in the brain of the brain (non-genetic)

• dietary- deficiency of essential fatty acids

• both nature and nurture contribute

Case study: Genetics of intelligence

• need a standardized measure of intelligence

• intelligence quotient (IQ)

• but does not measure all forms of intelligence

• however, a strong correlation between IQ and success at school

• twin studies show a heritability of around 50%

• moderate influence of genetics

• 25% comes from the shared environment for the twins

• 25% from their unique environment

• heritability increases with age (less than 40% at age 9 but as high as 80% beyond age 20)

• suggests that the environmental effects are more significant earlier in life