Week 9 - Genes and behaviour v2 PDF

latrobe.edu.au PSY1BNA Genes and behaviour Week 9 La Trobe University CRICOS Provider Code Number 00115M latrobe.edu.au Overview  What genes are, how do genes work, and how genes are transmitted to offspring  Mendelian genetics and Mendelian inheritance in humans  Cell division by mitosis and mei...

latrobe.edu.au PSY1BNA Genes and behaviour Week 9 La Trobe University CRICOS Provider Code Number 00115M latrobe.edu.au Overview  What genes are, how do genes work, and how genes are transmitted to offspring  Mendelian genetics and Mendelian inheritance in humans  Cell division by mitosis and meiosis  Analysis of autosomal recessive traits, autosomal dominant traits  Sex linked inheritance and analysis of X-linked dominant/recessive traits  Variation in gene expression  The current status of human behaviour genetics latrobe.edu.au Recommended reading See reading list on LMS Freberg, L. A. (2016). Discovering behavioural neuroscience: An introduction to biological psychology (3rd ed). Chapter 5 Breedlove, S. M., & Watson, N. V. (2020). Behavioral neuroscience (9th ed). Sunderland, MA: Sinauer Associates, Inc). Appendix A1-3 latrobe.edu.au Relevant animations  Molecular Visualisations of DNA Molecular Visualisations of DNA | WEHI  DNA Central Dogma Part 1 – Transcription DNA Central Dogma Part 1 - Transcription | WEHI  DNA Central Dogma Part 2 – Translation DNA Central Dogma Part 2 - Translation | WEHI  Chromosome and Kinetochore Chromosome and Kinetochore | WEHI Haemoglobin and Sickle Cell Anaemia Haemoglobin and Sickle Cell Anaemia | WEHI Part 1 Classical Genetics latrobe.edu.au The Science of Genetics A science about similarities and differences The study of a material that influences how organisms develop, function, and behave Hereditary material that passed from parent to offspring during reproduction Hereditary material is a physical link between generations latrobe.edu.au Hereditary Material Defining feature: it passes from one generation to the next Three properties of the hereditary material: Must be able to replicate Must contain information to guide the development, functioning, and behaviour of the organism Must be able to change latrobe.edu.au Levels of Genetic Analysis Classical genetics The period prior to the discovery of DNA Molecular genetics Chemical identification of genes Population Genetics Assessment of genetic variability in a population latrobe.edu.au Genetics and the World Genetics in agriculture and in medicine Discoveries in genetics are changing procedures and practices in agriculture and medicine Genetics in society Advances in genetics are raising ethical, legal, political, social, and philosophical questions latrobe.edu.au Three Great Milestones in Genetics The discovery of rules governing the inheritance of traits in organisms The identification of the material responsible for this inheritance and the elucidation of its structure The comprehensive analysis of the hereditary material in humans and other organisms latrobe.edu.au Genes and the Rules of Inheritance Gregor Mendel (1822 – 1884) Austrian monk, lived in the nineteenth century Studied the inheritance of different traits in peas Hybridization experiments with plants Existence of hereditary factors responsible for the traits  We now call these factors genes latrobe.edu.au The Structure of DNA Francis Crick and James Watson What is a gene? Genes consist of substances called nucleic acids Elementary building blocks of nucleic acids: nucleotides 1953 – the discovery of the double helix structure of DNA latrobe.edu.au The Structure of DNA Structure of a Nucleotide The DNA Molecule latrobe.edu.au The Human Genome Project  Sequencing DNA and cataloguing genes Worldwide effort to determine the sequence of approximately 3 billion nucleotide pairs in the human DNA Human genome contains around 30,000 genes These genes have been catalogued by location, structure, and potential function latrobe.edu.au Mendel’s Study of Heredity His experimental material was the garden pea Easy to grow plant Special flower petals enforce self-fertilization Individual pea strains are highly inbred displaying little genetic variation from one generation to the next Such strains are called TRUEBREEDING latrobe.edu.au Monohybrid Crosses The principles of dominance and segregation Cross fertilization of tall and dwarf pea plants First generation: all plants were tall Self-fertilization of first generation plants Second generation: tall and dwarf plants, 3:1 ratio latrobe.edu.au More Monohybrid Crosses latrobe.edu.au Conclusions from Monohybrid Crosses First generation hybrids (tall plants only) carried a latent genetic factor (for dwarfness) Latent factor: recessive Expressed factor: dominant Self-fertilization of monohybrid crosses Re-emergence of original traits Each trait controlled by a heritable factor that existed in two forms (genes and alleles) Alleles are alternate forms of a gene Parental strains (true-breeding plants): two identical copies of a gene Homozygous Zygote inherit two different alleles – one from the mother and one from the father – during fertilization Offspring is heterozygous latrobe.edu.au Dominant and Recessive Traits latrobe.edu.au The Principles of Dominance and Segregation The principle of dominance: in a heterozygote, one allele may conceal the presence of another They control the phenotype even when they are present in a single copy The principle of segregation: in a heterozygote two different alleles segregate from each other during the formation of gametes This principle is about genetic transmission latrobe.edu.au Dihybrid Crosses The principle of independent assortment Experiments with plants that differed in two traits (colour and texture of seed) First generation: all same Second generation: all possible combinations of colour and texture present latrobe.edu.au The Principle of Independent Assortment The alleles of different genes segregate independently of each other Each gene segregates its alleles These segregations are independent of each other (there is no connection between the segregation events of the two genes) latrobe.edu.au Applications of Mendel’s Principles: The Punnett Square Method latrobe.edu.au Applications of Mendel’s principles: The Forked Line Method latrobe.edu.au Snapdragon-Incomplete Dominance Two true-breeding plants (red and white flowers) First generation: all plants have pink flowers Second generation: red, pink, and white flowers The flowers of heterozygotes are pink because the alleles are not strictly dominant or recessive latrobe.edu.au Mendelian Principles in Human Genetics Part 2 Molecular and Cellular Genetics latrobe.edu.au Molecular and Cellular Genetics DNA and the Molecular Structure of Chromosomes Replication of DNA and Chromosomes From proteins to phenotypes Brief overview of cell structure Cell cycle Interphase Mitosis – growth and cell replacement Cytokinesis Meiosis - cell division as a basis for sex 28 latrobe.edu.au Hereditary Material (summary) Must be able to replicate Must contain information Must be able to change Genes consist of nucleic acids 29 latrobe.edu.au Chemical Bonds in DNA 30 latrobe.edu.au Genome Size of Different Organisms 31 latrobe.edu.au Chromosome Structure in Eukaryotes DNA is packaged into several chromosomes Each chromosome is present in two copies (diploids) In humans the length of DNA in a haploid cell is about 1m This DNA is subdivided among 23 chromosomes The size of a single chromosome varies between 15 and 85 mm in length 32 latrobe.edu.au Chemical Composition of Chromatin Chromatin isolated from interphase nuclei Chemical analysis: DNA RNA Histones (important in chromatin structure) Non-histone proteins (important in regulating gene expression) 33 latrobe.edu.au Chromatin and chromosome structure 34 latrobe.edu.au DNA Packaging and histones 35 latrobe.edu.au Transfer of Genetic Information The central dogma of biology: is that information stored in DNA is transferred to RNA molecules during transcription and to proteins during translation. 36 latrobe.edu.au Transfer of Genetic Information 37 latrobe.edu.au Four Levels of Protein Structure 38 latrobe.edu.au Different Shapes of Red Blood Cells 39 latrobe.edu.au Cell structure and function Cells differ widely in their size, shape, function, and life cycle However, all cells are fundamentally similar to one another Plasma membrane, cytoplasm, membranous organelles, membrane-bound nucleus Cell structure and function are under genetic control Many genetic disorders cause changes in cellular structure or function 40 latrobe.edu.au Main function of Organelles Nucleus genetic information - DNA Nucleolus produces ribosomal RNA Endoplasmic reticulum - Smooth produces phospholipids Endoplasmic reticulum - Rough lysosomal enzyme synthesis Ribosomes aids production of protein Golgi apparatus packages proteins Secretory vesicles protein hormonal store Lysosome digests cellular materials Mitochondria energy production 41 latrobe.edu.au Mendel’s principles Each parent contribute only one gene for each trait. Two copies of a gene separate from each other during the formation of egg and sperm. Only one copy of each gene is present in the egg or sperm. When egg and sperm fuse together at fertilization, the genes from the mother and father become members of a new gene pair in the offspring. latrobe.edu.au Regulation of gene expression Gene expression: a process by which a genetic information stored in the DNA converted into a functional gene product – a protein. Steps in gene expression: Transcription Translation Regulating gene expression gives the cell control over its function and structure. It is the basis for cellular differentiation. latrobe.edu.au Regulation of gene expression Housekeeping genes: expressed in all cells. They are transcribed at the same level in each cell. They code for proteins that are essential for basic functions that all cells need to survive: GAPDH (enzyme in the glycolytic pathway) Beta-actin (structural protein – cytoskeleton) Albumin (transport protein) Other genes are expressed selectively depending on the type of the cell. DNA methylation: forming compact, inactive chromatin, physically preventing transcription. latrobe.edu.au Chromosome structure Chromosomes are made up of DNA and protein (histons) tightly wrapped up in one package. Duplicated chromosomes are connected by the centrosome and are called sister chromatids. latrobe.edu.au Cell cycle Cells in the body alternate between two states: division and non division Time between cell divisions varies from minutes to months or even years Sequence of events from division to division is called the ‘cell cycle’ Cell cycle consists of 3 parts: Interphase - time between cell division Mitosis - division of the chromosomes Cytokinesis – division of cytoplasm 46 latrobe.edu.au Phases of the cell cycle latrobe.edu.au Types of Cell Division 48 latrobe.edu.au Mitosis Essential process in humans and all multi cellular organisms Some cells retain their capacity to divide throughout their life cycle Some cells no longer divide once they reach adulthood Cells in bone marrow continually move through cell cycle – 2 million red blood cells per second Skin cells divide to replace dead cells Muscle cells – enter G0 and do not divide Number of cell divisions is under genetic control Progeria – a condition associated with accelerated aging 49 latrobe.edu.au The four Stages of Mitosis 50 latrobe.edu.au Human Karyotype 51 latrobe.edu.au Meiosis Genetic information we inherit comes from two cells: sperm and egg In mitosis, each daughter cell receives two copies of each chromosome Cells with two copies of each chromosome – diploid (2n) = 46 chromosomes In meiosis, members of a chromosome pair separate from each other and each cell receives a haploid (n) set of 23 chromosomes 52 latrobe.edu.au Meiosis Haploid cells form gametes (sperm and egg) Fusion of two gametes in fertilization restores the chromosome number to 46 Distribution of chromosomes is an exact process Each gamete contains one member of each chromosome pair Not a random selection of 23 of the 46 Two rounds of division accomplish the precise reduction in the chromosome number Meiosis I and Meiosis II 53 latrobe.edu.au Meiosis Meiosis maintains a constant chromosome number from generation to generation Cells in the testis and ovary (germ cells) undergo meiosis and produce gametes Diploid (2n) cells undergo one chromosomal replication followed by two divisions four cells, each of which contains the haploid (n) number of chromosomes 54 latrobe.edu.au Meiosis 1 – separates chromosome pairs Before cells enter meiosis the chromosomes replicate during interphase Prophase 1 – chromosomes coil and become visible Metaphase 1 – members of each homologous pair line up across the middle of the cell Anaphase 1 – members of each pair separate from each other and move toward opposite poles Cytokinesis – after telophase 1 (nuclear envelope forms) Two haploid cells are produced 55 latrobe.edu.au Meiosis 2 – separates sister chromatids Beings with haploid cells Each unpaired chromosome consists of two sister chromatids joined by a centromere Prophase 2 – chromosomes coil and spindles form Metaphase 2 – each chromosome is attached to a spindle fibre at centromere Anaphase 2 – centromere of each chromosome separates for the first time Cytokinesis – after telophase 2 Two haploid cells are produced 56 latrobe.edu.au Combining genes New combinations of parental genes are produced by random assortment of maternal and paternal chromosomes Each pair of chromosomes carried contains one from mother and one from father In metaphase I the members of each pair line up at random with respect to all other pairs Arrangement of any chromosomal pair can be maternal - paternal or paternal - maternal Cells produced in meiosis I are much more likely to receive a combination of maternal and paternal chromosomes rather than only maternal or only paternal 57 latrobe.edu.au Production of Gametes 58 latrobe.edu.au Definitions locus - the specific location of a gene on a chromosome (locus - plural loci) somatic cell - all body cells except reproductive cells gamete - reproductive cells (i.e. sperm & eggs) homologous chromosome - chromosome of the same size and shape which carry the same type of genes diploid (2n) - cellular condition where each chromosome type is represented by two homologous chromosomes haploid (n) - cellular condition where each chromosome type is represented by only one chromosome chromatid - one of two duplicated chromosomes connected at the centromere centromere - region of chromosome where microtubules attach during mitosis and meiosis latrobe.edu.au Summary Meiosis Fertilization Each cell duplicates its chromosomes, and then divides to yield 2 daughter cells - splitting the paired chromosomes into separate cells. Then, the daughter cells divide again, splitting the chromosomes into single chromatids. Germ cells combine to form a cell with the full complement of chromosomes. Mitosis The chromosomes in the fertilized egg duplicate, and the cell divides, yielding 2 identical daughter cells. Part 3 Sex Chromosomes and Inheritance latrobe.edu.au Sex chromosomes Females: XX Males: XY Autosomal chromosomes: all but one pair of chromosomes, numbered 1 through 22. Sex chromosomes: one pair of chromosomes, XX in females and XY in males. The Y chromosome is small and contains few, if any, genes other than those that cause the individual to develop as a male. latrobe.edu.au Sex chromosomes Sex-linked genes: genes on the sex chromosomes. Sex-limited genes: genes that exert their effects in one sex only, or genes that exert a stronger effect in one sex than in the other. Sex limited genes can reside on autosomal or sex chromosomes and both sexes will have the gene. These genes exert their effects only after activation by the sex hormones testosterone or estradiol. These genes are responsible for sexual dimorphism. latrobe.edu.au Y chromosome Sex determining chromosome. 60 million base pairs (.38% of the total DNA) 78 genes only: Some encode proteins used by all cells. Others encode proteins that appear to function only in the testes. SRY (Sex-determining region Y) gene. It is the master switch that triggers the events that converts the embryo into a male. Without this gene the embryo develops into a female instead. The mutation rate of the Y chromosome is 4.8 times higher than any other chromosome. latrobe.edu.au X chromosome 153 million base pairs: 5% of total DNA in woman. Contains about 2000 genes. Only few has a role in sex determination. latrobe.edu.au X chromosome Inheritance of genes located on the X chromosome: Males have only a single copy of the X chromosome. Almost all genes on the X chromosome have no counterpart on the Y. Any gene on the X, even if recessive in females, will be expressed in males. latrobe.edu.au X chromosome inactivation Human females inherit two copies of every gene on the X chromosome. Males inherit only one. Are males at a disadvantage in the amount of gene product their cells produce? Females have only a single active X chromosome in each cell. latrobe.edu.au “Recessive” and “Dominant” alleles Dominant Recessive latrobe.edu.au Simple inheritance Heritable human traits have two subtypes: Qualitative Blood type Quantitative Skin colour Eye colour Personality traits Intelligence latrobe.edu.au Monogenic and polygenic traits Monogenic trait: controlled by a single gene variation. 1 allele for a dominant gene or a pair of alleles for a recessive gene: Eye colour, colour blindness, taste sensitivity. Polygenic trait: controlled by multiple genes. Each dominant gene or a pair of recessive genes make a unique contribution: Height, weight, intelligence. latrobe.edu.au Multi-factorial and complex traits Multi-factorial traits: controlled by two or more genes and show interactions with the environment. Inherited in a Mendelian fashion but interaction with the environment produces varying phenotypes. Complex traits: describe conditions where the relative contribution of genes and environment have not been determined. Hypertension, obesity, cardiovascular diseases. latrobe.edu.au Multi-factorial traits Multi-factorial traits have several important characteristics: Traits are polygenic. Controlled by several genes. Genes controlling the trait act additively, each contributing a small amount to the phenotype. Environmental factors interact with the genotype to produce the phenotype. latrobe.edu.au Nature versus nurture How much of a given phenotype is caused by heredity and how much by the environment? Intelligence; Gender identity; Criminal behaviour; Different types of addiction. Each individual has a unique genotype and has been exposed to a unique set of environmental conditions. This cannot be determined. Threshold model is used to study multi-factorial traits. latrobe.edu.au Inheritance of complex traits Threshold model was developed to predict the likelihood that the trait will be expressed. Additive effects are controlled by separate genes. Effects of genes combine to produce a unique phenotype. Additive effects can be examined in a liability threshold. latrobe.edu.au Threshold model Liability is distributed among individuals in a bell shape curve. Those with liability above a certain threshold develop the disease. Threshold can be reached by genotype (more genes → higher risk) Environmental factors (alone). Combination of genetic and environmental factors (most common) Model is useful in explaining the frequency of certain disorders and congenital malformations. Evidence for a threshold model comes mainly from family studies. latrobe.edu.au Studying behaviour Nervous system is the focus of behavioural genetics. Mutations that disrupt metabolic pathways or interfere with the synthesis of essential gene products can influence the function of cells and alter phenotypes. If the nervous system is part of the phenotype then behaviour will be affected. Many disorders affect the nervous system that in turn affect behaviour. latrobe.edu.au Concluding remarks Genetic information is stored in molecules of DNA The particular sequence of nucleotides will determine protein structure Genes exist in different forms: alleles Cell differentiation is determined by the set of genes that are active in the particular cell Genetic mutations can cause disorders that affect behaviour Part 4 Genetic Mutation Not Assessed Content latrobe.edu.au *Overview of Genetic Mutation* DNA replication and alteration Gene regulation Translocation Alleles Sex chromosomes Monogenic and polygenic traits Multifactorial and complex traits Heritability Genetic disorders Single gene disorders Polygenic disorders latrobe.edu.au *Beyond Mendel’s Laws* Special patterns of inheritance: Linkage and recombination; Gene conversion; Translocation; Spontaneous mutations; Genetic anticipation; Genomic imprinting; Mitochondrial DNA: Mitochondrial inheritance; Defective mitochondrial DNA; latrobe.edu.au *Linkage* When gametes are formed by meiosis, chromosome pairs are separated and randomly sorted into gametes. Linkage occurs when genes for multiple traits are located on the same chromosome and are passed on as a group. latrobe.edu.au *Recombination* Recombination occurs when chromosomes are physically pressed together during meiosis – swapping genetic material between paired chromosomes before they are segregated in separate gametes. latrobe.edu.au *Gene conversion* Involves the transfer of DNA sequence information from one chromosome to the other. The donor chromosome alters the sequence of the recipient chromosome, but its own DNA remains unchanged. latrobe.edu.au *Translocation* Exchange of genetic material between nonhomologous chromosomes. Balanced translocation: A reciprocal exchange of genetic material between the two chromosomes. Unbalanced translocation: One chromosome gaining material while the other loses that genetic material in the exchange process. latrobe.edu.au *Robertsonian translocation* latrobe.edu.au *Spontaneous mutations* Permanent transmissible changes in the genetic material called mutations. Induced mutations: Caused by exposure to exogenous factors, such as viruses, chemicals, or radiation. Spontaneous mutations: Errors in the DNA sequence that occur during replication. latrobe.edu.au *Genetic anticipation* Triplet repeat expansion disorders: Huntington’s disease – CAG repeat on chromosome 4. Fragile X syndrome – CGG repeat on chromosome X. Myotonic dystrophy – CTG repeat on chromosome 19. Inheritance pattern is Mendelian. The triplet repeat expands progressively in successive generations. The symptoms may occur at an earlier age. Successive generations exhibit increasingly severe forms of these conditions. latrobe.edu.au *Germinal mosaicism* Very rare condition. One parent gametes carry a genetic defect, but this defect is not found in somatic cells – parent is unaffected. It results from a spontaneous mutation of the gamete producing germ cells. Genes are passed on from the parent to the offspring in a Mendelian pattern. Duchenne muscular dystrophy has germ cell origin in some cases. latrobe.edu.au *Genomic imprinting* Sometimes paternally or maternally inherited DNA sequences can result in different phenotype. Paternally inherited Huntington’s disease: earlier onset and more severe symptoms than maternally inherited Huntington’s disease. Deletion of genes from maternal chromosome 15 causes Angelman syndrome. Deletion of same genes from paternal chromosome 15 causes Prader-Willi syndrome. latrobe.edu.au *Mitochondrial DNA* Mitochondrion is the power plant of the cell producing cellular energy and regulating cellular metabolism. Mitochondria are abundant in egg cells but not in the sperm. Maternal mitochondria passed on to offspring. Inheritance pattern of mitochondrial diseases: All offspring will inherit the condition carried by their mother. Traits are never passed on through a male.