Linkage, Mapping, and Mutations Genetics Linkage, Mapping, and Mutations

Review… Different organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes in their somatic (body) cells and 23 single chromosomes in their gametes (sex cells) this makes somatic cells diploid and gametes haploid. The sex of an organism is determined by the 23rd chromosome. It is either XX or XY; the Y is found only in males (exceptions later) Chromosomes are made up of DNA (deoxyribonucleic acid); long strands of DNA are folded up and tightly packed to form chromosomes. Genes are short sections along the strand of DNA that code for a particular job or function. Genes=DNA=Chromosomes…it’s all the same material (just different pieces have different functions). All genes together (meaning all DNA and all chromosomes too) make up an organism’s genome.

Chromosomes, DNA, and Genes Are threadlike structures found in the nuclei of cells Made up of genes arranged in a linear sequence (DNA) Are made up of DNA molecules DNA: The primary genetic material of all cells Deoxyribonucleic Acid Makes up chromosomes Gene: A sequence of nucleotides to which a specific function can be assigned Short segment of DNA All genes together make up a genome

To put it all into perspective…

New Vocabulary Allele Amniocentesis Autosome Base Pair Chromosomal Aberration Clone Codon Crossing Over Down’s Syndrome Duplication Electrophoresis Frameshift Gene Genome Genotype Homologous Independent Assortment Inversion Inversion Polymorphism Karyotype Klinefelter’s Syndrome Linkage

New Vocabulary continued… Linkage Group Locus Marker Multiple Alleles Multiple-Factor Inheritance Mutant Mutation Mutator Gene Pedigree Recombinant Type Regulatory Gene Sex-Linkage Sickle-Cell Anemia Sickle-Cell Trait Somatic Cells Structural Gene Transformation Transition Translocation Transposition Transversion Turner’s Syndrome

DNA and Gene Function DNA=Life’s Code Makes up genes Controls traits Forms chromosomes Found in the nucleus of all cells Chromosomes and their corresponding genes control the cell Genes are under the control of the DNA code and the code itself “makes” the genes through DNA replication, transcription, and translation

Genes Short segments of DNA that code for specific traits (hereditary characteristics) Made up of varying numbers of base pairs (proteins that make up DNA: AGTCU) The order of the base pairs determines the “code” or genetic information and function of the gene Genes “code” for the expression of specific traits (ex. eye color); so if we know the eye color of an individual, we know its genotype or which genes it is expressing (remember genes can be dominant or recessive and there are two genes for each trait, one per chromosome)

Q: Why do sex cells have single chromosomes with single genes and body cells have pairs of chromosomes with one gene per chromosome (2 for each trait)? A: Because during fertilization the zygote receives one set of chromosomes from the female egg and one set from the male sperm making one complete set. Body cells need the complete code in order to divide and function because they will never be fertilized.

Individuals inherit genes one from each parent Individuals inherit genes one from each parent. These genes (inherited on the X and/or Y chromosomes) are said to be “sex-linked”. Scientists have discovered specific genes on the sex chromosomes that code for particular traits. Ex. color vision, blood clotting, tooth color, skin dryness. These are all traits that can be attributed to a specific chromosome. How an individual’s phenotype is expressed tells us about it’s genotype. But, what about an individual, an embryo for example, that does not yet have an expressed phenotype? Or, what about traits that cannot be seen with the naked eye in children and adults? We have developed other ways to look at an individual’s genotype. Why might this be important? Ex. genetic counseling (i.e. prediction of heritable traits whether offspring will be healthy or not) How do we acquire this information? Amniocentesis (i.e. take a DNA sample from the developing fetus and look at its chromosomes) How do we look at chromosomes and genes? Gene Mapping and Karyotyping

Karyotype The chromosomal complement of a cell or organism, characterized by the number, size, and configuration of the chromosomes (i.e. how many chromosomes an individual has and the structure of each chromosome) Individuals may have errors in the number and/or composition of chromosomes These are called chromosome mutations

Q: Why is it that sometimes offspring do not closely resemble their parents? They may not even resemble their other siblings, but sometimes they do?

Independent Assortment?? Genes on different chromosomes assort independently, but are genes on the same chromosome always inherited together? Chromosomes assort independently, but not genes…why? Crossing over during meiosis I allows offspring to have characteristics not found in either parent. Each chromosome is a group of linked genes. Some genes are inherited together and some are not.

Thomas Hunt Morgan & Alfred Sturtevant Used drosophila (fruit flies) to experiment with independent assortment of genes Q: Why use fruit flies? A: They have a short reproduction generation and reproduce in large numbers They found that genes appeared to be “linked” to each other…that is, certain groups of genes were always inherited together Furthermore, the linkage groups appeared to assort independently as well (due to crossing over) They hypothesized that crossing over is exhibited more frequently with genes that are further apart and that those genes that are closer together will be inherited together more often.

Thomas Hunt Morgan & Alfred Sturtevant Therefore, the frequency of certain traits being phenotypically observed should reflect the distance between those genes on a chromosome By calculating the frequency of phenotypes in a cross of individuals with a known genotype, we are able to “map” genes on their respective chromosomes

Gene Mapping Genes that are very close together are almost always inherited together Genes that are far apart are less likely to be expressed together By looking at the frequency of each combination of alleles, we can determine which genes are inherited together and how close or far apart they may be This recombination of alleles and expression of different phenotypes is important for genetic variation Linkage maps are the relative positions of genes on their chromosomes Historically this has been done using pedigrees for humans… Q: Why might this be an ineffective way to map human genes? A: Humans have a long generational time period (do not reproduce as early/long time to mature), reproduce in small numbers (takes many to look at many different phenotype frequencies), humans have many chromosomes (23 pairs) and therefore many genes (approx. 30,000-40,000 genes) Biotechnology (ex. polymerase chain reaction) has allowed for more efficient mapping techniques

Example… http://www.brown.edu/Courses/BI0020_Miller/week/4/gene-mapping.pdf Mapping allows us to predict the likelihood that certain traits will be passed on to the next generation This is important especially for those sex-linked traits (ex. hemophilia) and for genes that cause disorders (ex. Down’s Syndrome) Remember, first we must know the parent-type (i.e. the parent’s genotype for the particular trait) We find this by looking at pedigrees and other generations to see which relatives, if any, have phenotypically expressed the trait in the past

Genetic Disorders Chromosomal Mutations (error in number, size, and/or composition) Sex-Linked Serious disorders controlled by genes on the X or Y chromosome Gene Mutations A change in the DNA sequence (due to an error during protein synthesis) Point mutations Insertion, Deletion, Substitution Frameshift mutations Insertion or Deletion (causes a misread) The wrong base gives the cell the wrong message Autosomal Occur in non sex-cells (ex. dyslexia)

Genetic Disorders in humans Conditions caused by abnormal or nonfunctioning alleles Albinism (lack of pigment in skin, hair, eyes) Cystic fibrosis (excess mucus in lungs, digestive track, and liver; increased susceptibility to infections) Galactosemia (accumulation of galactose (sugar) in tissues; mental retardation; eye and liver damage) Phenylketonuria (PKU) (accumulation of phenylalanine in tissues; lack of normal skin pigment; mental retardation) Tay-Sachs Disease (lipid accumulation in brain cells; mental deficiency; blindness; death in early childhood) Achondroplasia (one form of dwarfism) Huntington’s Disease (mental deterioration and uncontrollable movements; symptoms usually appear in middle age) Hypercholesterolemia (excess cholesterol in blood; heart disease) Sickle Cell disease (misshapen, or sickled, red blood cells; damage to many tissues)

Genetic Disorders in humans Sex-Linked conditions Colorblindness (most commonly found in males; linked to the Y chromosome; inability to distinguish certain colors) Hemophilia (linked to 2 genes on the X chromosome; missing protein for blood clotting) Duchenne Muscular Dystrophy (progressive loss and weakening of skeletal muscle; defective gene) Disorders caused by chromosomes Down Syndrome (trisomy of chromosome 21 = mild to severe mental retardation) Turners’ Syndrome (females having only one X = sterile, lack sex organ development) Klinefelter’s Syndrome (males having and extra X = cannot reproduce)

Important! Using this information, scientists are able to not only predict disease but are also able to treat and/or prevent it by manipulating human DNA. This is done using techniques like: Recombinant DNA (gene splicing) Gene Therapy (inserting a healthy gene) Cloning (copying DNA) So why not do it? Is the manipulation of DNA a worthwhile cause? Where do we stop? Should people determine the sex of their babies or what color eyes they should have? You decide…

http://teachertube. com/viewVideo. php http://teachertube.com/viewVideo.php?video_id=67100&title=Who_Made_Who_

Assignment… Find a current event topic in the newspaper, a magazine, or from an educational/research-based website relating to genetic research. Your topic must raise one or more important ethical issues. Analyze your topic from both perspectives (i.e. pros and cons). Write a 2-3 page essay evaluating the genetic research from both points of view. You do not have to form your own personal opinion, this is not a debate. We want to see both sides of an argument This assignment will be discussed in groups on day 4 and will also be individually presented to the class, so make sure you have a firm understanding of the concept as well as the ethical issues involved.