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Lecture 9

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Biological Sciences
Patrick Mc Gowan

BIOC14: LECTURE 9 03/27/2014 ENVIRONMENTAL EPIGENETICS • Mechanisms above gene expression like DNAmethylation or histone modifications • Can have stochastic changes in epigenetic cells that accumulate • Some epigenetic mechanisms can be directly acted upon by env factors o Psychiatric diseases Epigenetics of major Psychiatric Disease • Genetically, we’re similar, epigenetically, we’re diff • Epigenetics is new and competes with traditional paradigm • Dizygotic twins share 50% of segregating polymorphisms, not DNA • Humans and chimps share 90% of DNA • 99.5% DNAshared in dizygotic dna • Monozygotic twins, genetically identical, but phenotypically diff o 1 can have cancer or schizophrenia and the other may be fine, therefore there must be env factors affecting them • Dizygotic twins exhibit larger differences phenotypically (diff in concordance = heritability of dna sequence) • Paradigm – research program, how diff probs should be addressed • Genetic factors, predisposing factors and env hazards interact to cause diseases • Env studies – easy to identify association btw env factor and phenotype like stress and depression o Is this association causative? Hard to understand • The depression may expose people to the stressful events • Smoking looks like an env factor, but heritability of smoking is 60% • Only env factors …… • Genome wide association studies o Convert info to heritability o Autism heritability 90%, schizo – 70%, bipolar 80% • DNAcentred paradigm successful in cystic fibrosis o If father is affected of type 1 diabetes, chances of offspring developing it is higher than if mother is affected • Mendelian disorders are simple relative to complex disorders Epigenetics • Chromosomes – stuff cells share when they divide • DNAstrands are important components of chromosomes • Chromosomes consist of nucleosomes • Histons and dna seq can be chemically modified (methylated, phosphorylated, etc) • Diff attachments to diff amino acids • DNAcan be modified o Methylation of cytosines o Carboxycytosines (4 diff types of medication) o Dna seq behaves diff depending on flavour of cytosine there • Regulation of function • 2 identicaly genes (dna seq) o 1 case – modified cytosines in promoter region BIOC14: LECTURE 9 03/27/2014 o 2 case – methylated cytosines in promoter regions  Inactivated gene • Genetically identical organisms have large phenotypic differences by 1 gene modification • Genome may be same, function is diff bc of epigenetic factors o Epigenetic factors contribute to phenotype o Epigenetic factors are inherited parents to offspring, but before thought not possible o Epigenetic sequences can be modified by developmental programs, hormones, env, stochastic events, unline dna o Partial stability is important….. • Same petri dish – can’t blame env, will see genetically identical cells very diff from an epigenetic view due to stochastic events o Check this part • Epigenomic profile o 40 000 base pairs, some places have high density of cytosines, others are flat o 140Mb – entire chromosome, each represents a diff individual • Monozygotic twins would accumulate around 0 line bc no differences o May be coming from diff environments o Inbred animals – genetically identical, see the same thing, means eliminate genetic variation and env variation and still see epigenetic difference bc of accumulated stochastic events and being amplified o Smoking is a risk factor for lung cancer  Don’t know about risk factors for schizophrenia  Env factors may be important, but not only env factors that cause phenotypic diff • Dizygotic twins have large phenotypic diff • The more similar are at each locus, the higher the ICC will be • Dizygotic twins are less similar and more diff o Means that epigenetic zygotic effect
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