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Chapter 5

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University of Toronto Scarborough
Janelle Leboutillier

CHAPTER 5 Personality traits have strong roots in genetics. - Kegan noted that shy adolescents (compared with bold one) were more likely to have allergies, be tall and thin, have a faster heart rate and be pale and blue-eyed. Genetics and Behavior 100 trillion cells in body Each cell (except blood/eggs/sperm) has 2 copies of genome. - Genome: a complete set of chromosomes - Genotype: the genetic composition of an organism - Interacts with environment to produce your phenotype. - Phenotype: the observable appearance of an organism - Chromosome: a strand of DNA found within the nucleus of a cell (23 matched pairs - 46 in all)  Deoxyribonucleic acid (DNA): molecules that compose chromosomes - Gene: a functional hereditary unit made up of DNA that occupies a fixed location on a chromosome  Gene expression: the translation of the genotype into the phenotype of a particular gene  Allele: alternative version of a particular gene (ex. Allele of blood type: A,B,O) o Homozygous: having two different alleles for a given gene o Heterozygous: having two different alleles for a given gene o Recessive allele: a gene that will produce its characteristic phenotype only when it occurs in a homozygous pair (ex. Type O blood) o Dominant allele: a gene that produces its phenotype regardless of whether its paired allele is heterozygous or homozygous  Imprinted gene: a gene of which only the mother’s or the father’s copy is expressed, but not both in the normal Mendelian sense o 1% of mammals’ genes o Implicated in a number of genetic disorders, behavioral disorders (e.g. autism and BP disorder) and vulnerability to cancer. nDNA mutates at a fairly regular rate, which makes it useful for the study of evolution. - Mitochondrial DNA originates from the mother. - Arguments suggesting human life first evolved in Africa is supported by mDNA analysis. - Although this method is ideal to identify human remains, other methods include study of DNA and dental records. - Using mDNA, positive identification of the remains of Jesse James was possible. o Used blood samples from 2 of his living maternal relatives. Different phenotypical traits result from interactions of alleles. - 3 alleles for blood type in population- A, B, O - 4 blood types: o A- AA/AO o B- BB/BO o O- OO o AB- AB From Genes to Proteins Adenine, Cytosine, Guanine, Thymine The complexity of humans does not arise from their number of genes - 20,000-25,000 genes in human genome - Yeast cells- 6000 genes - Flies- 13,000 genes - Plants- 26,000 genes Humans and other creatures differ in their rate of gene expression of genes in the brain. - Rate of human gene expression in the blood and liver are equal to those of a chimpanzee, but differs in the brain. - Humans also unique due to our proteome- set of proteins encoded and expressed by the genome. Sources of Genetic Diversity Meiosis: cell division in sexually reproducing organisms that reduces the number of chromosomes in half in the reproductive cells, such as sperm, eggs, and spores. - Division leads to production of egg or sperm with one set of 23 chromosomes. - 2 (8,388,608) combinations of chromosomes. Linkage: the characteristic of genes located adjacent to one another to be passed along as a group. Crossing over: a process occurring during meiosis in which chromosomes exchange equivalent segments of DNA material. Mutations May occur in chromosome replication. Vast majority have little effect since: - There is some overlap in genetic encoding of amino acids. - Mutation may occur in DNA segments that don’t influence phenotypical traits - Mutation may result in a recessive allele o Inheriting a dominant mutant allele or 2 copies of a mutant recessive allele WILL affect phenotype. o If this conveys some advantage, this is likely to spread within the species. VV will make it disappear from the population. The Special Case of Sex Chromosomes Most active genes on Y chromosome are involved with male fertility. X- wide variety of genes Sex-linked characteristics result from genes on the X c that aren’t duplicated on the Y c. - E.g. recessive genes resulting in hemophilia - E.g. genes resulting in some forms of red/green color-blindness - Both located on X c. In genes on the X c (unlike in other c), a single recessive gene influences the phenotype when there isn’t a corresponding gene on the Y c. - This is why males are more likely to experience sex-linked disorders than females (since fndales are more likely to have a compensating dominant gene on their 2 X c). The lack of matching pairs for most genes on sex chromosomes have led to a phenomenon called X Chromosome Inactivation. - Since many genes on the X c are not duplicated on the Y c, females could produce double the amount of proteins compared to males. - To compensate for the imbalance, most genes one 1 X c in each female are randomly silenced during development. - The actual identity of the silenced X c genes varies from cell to cell and a small % escape silencing altogether. - An example: coloring of calico cats: o Only females can be calicos since the genes for orange or black fur area located in the same area of the X chromosome. o A male can have only orange or only black fur, but not both because he has only 1 X chromosome. o A female with orange on one X and block on the other X will be a calico. o In each cell, the fur color genes on 1 X c will be silenced. o As a result, the cats will have a random pattern of orange and black fur. Bocklandt et al suggested variations in the degree of x-inactivation of mothers may be related to the sexual orientation of sons. - In most cases, the number of cells in which the maternal X has been silenced is approximately same as the number in which the paternal X is silenced. - Extreme skew: some individuals have silenced the X from 1 parent in greater numbers. o More common among mothers who has give birth to gay sons (13%) than in those with heterosexual sons (4%). o 23% of mothers with 2 or more gay sons showed extreme skewing. Single Nucleotide Polymorphisms (SNPs) Researchers are interested in alleles whose genetic code differs in only 1 location- called SNPs. - Occurs when a sequence of nucleotides making up 1 allele differs from the sequence of another at just 1 point. e.g. APOE gene on chromosome 19 produces a protein that helps keep cholesterol levels low. - 3 alleles for this gene known as E , E and E . 4 - Each allele has 299 codons. 2 3 4 - The 122th codon encodes cystine in E and E , but argenine in E . - The 158 codon encodes argenine in E and E , but cystine in E . 2 These tiny differences many have significance in the development of disease. - The APOE SNP predicts a person’s risk for Alzheimer’s disease. 4 - A person with 2 E genes has 91% chance of developing Alzheimer’s (average onset age is 68). - 1 E gene- 47% chance at age 75. - No E gene- 20% chance at 84. The Roles of Heredity and Environment Heritability always refers to populations, not individuals. Hoekstra et al: individual differences in endorsement on autistic traits show substantial heritability (57%) Means: 57% of variation we see in the autistic traits of Dutch teens can be accounted for by their genetic differences. Adult male height- 81% heritable BMI- 59% heritable If the environment is constant, heritability of a trait is very high. Sorting out the contributions of heredity and environment is done by looking at monozygotic (identical) or dizygotic (fraternal) twins raised by adoptive parents. - Twins (unlike ordinary siblings) share the same environment before and after birth. - E.g. Minnesota study of twins reared apart o Critical finding: The identical twins were very similar regardless of whether they were raised apart. o Some traits were highly correlated between identical twins. E.g. number of ridges in a fingerprint. o Others had low correlations- nonreligious social attitudes. - Bouchard et al study o Jim Lewis & Jim Springer were identical twins adopted by separate families at 37 days of age and grew up not knowing each other until age 38. st o Both married 1 wives named Linda, whom they divorced to marry 2 wives named Betty. o Both had dogs named Toy and sons named James Alan. o Both enjoyed woodworking, watching stock-car racing and drinking Miller Lite beer. o Both had vasectomies, smoked, bit their fingernails and suffered from migraines. - 2 women cited in a 2001 American Press Report: o Both born March 13, 1941 and named Patricia Ann Campbell o Both had fathers who were bookkeepers named Robert o Both studied cosmetology, painted in oils, married military men. o Their weddings were 11 days apart and had children ages 19 and 21. o They weren’t related. Development Human- 100 trillion cells - 100 billon of those are brain cells 1 cell formed by merger of egg and sperm= zygote 2-8 weeks- embryo 8 weeks to birth- fetus 1 week after conception, the zygote has formed 3 differentiated bands of cells known as germ layers. - Outer layer: ectoderm  will develop into nervous system, skin, hair - Middle layer: mesoderm  connective tissue, muscles, blood vessels, bone, urogenital systems - Inner layer: endoderm  internal organs, stomach and intestines 3 weeks- cells in ectoderm along the dorsal midline begin to differentiate into a new layer called neural plate. - Remaining cells of ectoderm become skin. Cells differentiate in response to gene combinations and inducing factors (chemical signals from other cells). - Spemann and Mangold demonstrated that the inducing factors responsible for the differentiation of neural tissue from future skin tissue originated in an area of the embryo called the organizer region of the mesoderm. - They transplanted cells from the organizer region of one amphibian embryo near the ectoderm layer of a second/host embryo. o These transplanted cells followed their own pattern and became mesoderm tissue. o The transplanted cells also signaled the host embryo to form a 2 nd complete nervous system. More recent research has shown that without any contact with other embryonic cells, ectodermal cells will form neural tissue. - Skin only forms when ectoderm cells are exposed to a protein called bone morphogenetic protein (BMP). - Inducing factors released by the organizer region have the capacity to block BMP, resulting in the formation of neural tissue. As the ectodermal cells begin differentiation, a groove forms along the midline of the neural plate. - Further cell divisions produce 2 ridges of tissue on either side of the groove that eventually join to form a neural tube. After the tube has formed, development of mature nervous system proceeds in 6 stages: 1. Continued birth of neurons and glia 2. Migration of cells to their eventual locations in the nervous system 3. Differentiation of neurons in their various types 4. Formation of connections between neurons 5. Death of particular neurons 6. Rearrangement of neural connections Formation of Neurons and Glia Neurons and glia originate from cells locate in the ventricular zone (cell layer lining the inner surface of the neural tube). - These progenitor (reproducing) cells in the ventricular zone divide by mitosis causing this zone to thicken. - After week 7, the progenitors of the ventricular zone produce a daughter cell that remains in the zone and a daughter cell destined to migrate outward to form a neuron or glial cell. - Progenitor cells producing 2 additional progenitors divide along cleavage line that’s perpendicular to the ventricular zone surface. - In contrast, progenitor cells producing 1 progenitor cell and a migrating cell divide along cleavage line that’s parallel to the ventricular zone surface. o This means that the daughter cell to the outside will not be attached to the ventricular zone once division is complete and it’s free to migrate. o In humans, up to 250,000 new neural cells/min are born at this peak of cell formation process. Cell Migration - Journey isn’t random- guided by specialized progenitor cells called radial glia grow out from the ventricular layer to the outer margins of the nervous system like spokes of a wheel. o These cells retain ability to produce additional daughter cells. o 2/3 of migrating cells wrap around the radial glia and move along them. rd o The remaining 1/3 don’t follow the radial glia; they move horizontally. o Once migration is complete, radial glia pull back their branches (some remain in place throughout adulthood). - Migrating cells form the cerebral cortex in an inside-out fashion. o Cells destined for the outside layers must travel through the inner layers.  E.g. cell going to layer IV would have to bypass layers VI and V en route. - Journey of early migrating cells lasts only a few hours. - Cells going to the outermost layers need 2 weeks. - Knowing this, researchers can determine the timing of certain brain abnormalities with accuracy. o E.g. disarray found in the hippocampus found in schizophrenic patients might result in disruption in migration during the 2 nd trimester of pregnancy. Differentiation The neural tube undergoes 2 separate processes of further differentiation: Process 1: Differentiates the dorsal and ventral halves of the neural tube. - neurons in the ventral half develop into motor neurons - Dorsal half become sensory neurons - Organization of ventral tube into a motor system is under control of proteins called sonic hedgehog, which are released by a mesodermic structure called notochord (lies under the neural tube). o Notochord will eventually develop into vertebrae surrounding spinal cord. - Differentiation of dorsal neural tube into sensory neurons occurs in response to BMP. - The ventral sonic hedgehog and BMP extend through the hindbrain and midbrain. o Sonic hedgehog responsible for development of substantia nigra (in ventral half of midbrain). Process 2: Differentiates the neural tube along its rostral-causal axis. - This results in division of the nervous system into the spinal cord, hindbrain, midbrain and forebrain. - Differentiation of hindbrain is controlled by inducing proteins encoded by Hox genes. o Different Hox genes are expressed in different segments of the hindbrain which results in the development of specific cranial nerve nuclei. - The midbrain doesn’t show the same segmented organization found in the hindbrain- no Hox genes here. The mature organization of the cerebral cortex is a combination of internal generic factors and external inducing factors. O’Leary et al transplanted visual cortex into areas normally containing somatosensory cortex in newborn rodents. - The transplanted tissue later took the organization that’s normal for the somatosensory cortex. o i.e. some cortex is capable of being modified based on the type of input it receives. In other cases, the cortex develops independently of the input in response to intrinsic genetic factors. - Wassef et al genetically modified a strain of mice to express a marker gene only within the somatosensory cortex. - Marker genes readily produce an identifiable characteristic in cells carrying the gene (transplanted or in vitro). - When tissue from the somatosensory cortex of these mice was transplanted into the cerebellum or nonsomatosensory cortex area of normal mice- the marker was still expressed. Growth of Axons and Dendrites Once the neurons are in place, synapses must form. - Later developing axons follow the paths formed by earlier maturing axons. - Axons can sense the EC environment and prefer more adhesive surfaces. - Guidepost cells en route release chemicals that either attract or repel the growing axon. Roger Sperry demonstrated that axons followed some type of chemical pathway to their target. - Developing dendrites and axons end in growth cones or swellings, which have both motor and sensory abilities that help the developing branch find the right pathway. Growth cones have 3 basic structural parts: 1. Main body containing mitochondria, microtubules, other organelles 2. Filopodia- fingerlike extensions from core 3. Lamellipodia- flat, sheet-like extensions form the core (between filopodia). Filopodia and lamellipodia are capable of movement and ability to stick to elements of the EC environment, pulling the growing branches along behind them. Microtubules from the main body of the cone move forward as the cone extends, forming a new segment of axon or dendrite. Filopodia can signal the growth cone to move forward or backward or turn. - Also can respond to both attracting and inhibiting chemicals released by guidepost cells along the way. - E.g. growth of visual axons near the optic chiasm: o In humans, ½ of visual axons cross the midline at the optic chiasm and continue contralaterally. The other half remain on the same side and proceed ipsilaterally. o Godeont et al applied dye to the retina and charted the course of the dyed axons to the optic chiasm. o The growing axons responded to a group of guidepost cells located at the midline of the optic chiasm. o The contralateral axons made contact and passed these guidepost cells, whereas the ipsilateral axons were repelled by these cells. Axons growing in the same direction often stick together- fasciculation. - Molecules on the surface of growing axons (cell adhesion molecules- CAMs) - As cones approach their target, they form either dendrites or axon collaterals. - Experience will interact with intrinsic factors to fine-tune the connections. Formation of Synapses Sweat glands- mature sympathetic axons release Ach. Usually sympathetic axons release norepinephrine- the switch is induced by exposure to chemical signals originating in the target cells (glands). i.e. interaction with target cell influences the type of neurotransmitter released. Synapse formation at the neuromuscular junction: - Prior to contact, the muscle fiber has receptors for ACh. o Initially, the receptors are evenly spaced within the membrane. o After the synapse is formed, the receptors are densely clustered in synaptic sites. Mutant strains of mice lacking essential presynaptic substances fail to develop the normal clustering of ACh receptors- leads to death. Signals from the muscle fiber also affect developme
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