Classical (Mendelian) Genetics
Classical (Mendelian) Genetics (Ch. 9 - 13)
Chapter 9 - "Fundamentals of Genetics"
History of Genetics: Gregor Mendel (1822-1884)
Gregor Mendel's biography, "From Garden to Genome" (30 min) YouTube video
|1st identified plants with 7 trait differences |
Each group was bred "True" for each trait to be studied (purebred, or "homozygous") through self-pollination
Mendel cross-bred (hybridized) different plants to see what the offspring would look like...
1.) tall x short
2.) yellow x green seeds
3.) wrinkled seeds x smooth seeds
...and found he got predictable outcomes
- Mendel's success as a scientist was based on his careful scientific methods:
- Concentrating on one trait at a time, all traits are easily observed/measurable. ex: Color? Shape?
- Restricted Breeding: "made" male and female plants
- Controlled Fertilization: hand-pollinated (paint brush), and covered flowers
- Kept detailed records of crosses & offspring (painstaking data collection/recording)
- Through statistics, Mendel observed some repeatable ratios (probabilities) in offspring
- Provided the basis for 4 principles of heredity that still apply today!
- Homologous Chromosomes: chromosomes that carry corresponding genes, and associate in pairs; each is delivered from different parent
- Alleles: genes that have a contrasting effect on a characteristic (Mendel only worked with two contrasting alleles)
- Multiple alleles: traits with > 2 alleles for the same characteristic (example: A,B,O blood types)
- Dominance: the ability of one allelic form of a gene to be expressed over another
- Recessiveness: condition when one allele is masked by another, more dominant allele
- Genotype: particular combination of genes in an organism (Tt, TT, tt)= genetic makeup
- Phenotype: the appearance of an organism as determined by its genetic makeup
- Homozygous: both genes of a pair are the same (TT, tt); sometimes called "pure bred".
- Heterozygous: paired genes are not the same (Tt); sometimes called "hybrid".
- P1: parental generation
- F1: first filial generation of offspring
- F2: second filial generation of offspring
1: "Inherited characteristics are controlled by factors that occur in pairs." (each individual carries a pair of alleles - alternate forms of the same gene- on homologous chromosomes)
2: "Principle of Dominance and Recessiveness" : "One factor in a pair may mask the other, preventing it from having an effect"(only the dominant allele of a gene is expressed, although a recessive allele may be carried)
3: "Law of Segregation" : " A pair of factors is segregated, or separated, during the formation of gametes"(each reproductive cell receives only one of a pair of alleles- to be passed on to offspring)
4: "Law of Independent Assortment" : " Factors (genes) separate and are distributed to gametes completely separate from other genes";example: tall (plant height) gene is not connected to pea color gene. animation linked here
funny: Mendel Rap (YouTube)
- inventor: R.C. Punnett
- a way to calculate (statistically) the probable outcome of a cross between two parents with known genotypes
- A simple way to determine genetic combinations that can result from a particular cross
- draw squares with four quadrants, each quadrant represents a 25% chance of occurrence
Example: Fruit flies (Drosophila) in our lab have two possible eye colors, red (which is dominant) and sepia (recessive) = there are two ALLELES for this eye color gene, R and r.
if you cross two purebred parents (one of each eye color), you can make a Punnett square to predict the eye color of the offspring (F1)
(a) homozygous red x homozygous sepia RR x rr
(b) 2 heterozygous parents Rr x Rr(c) ...or THIS (below), a cross between a homozygous dominant (RR) and a heterozygous dominant (Rr):
...this is called a Monohybrid Cross- when only one trait (with contrasting alleles) is considered in a cross; a shockwave animation of How To Use Punnett Squares
see textbook for further explanation (pages 182-183)
CO DOMINANCE (or incomplete dominance)
Sometimes more than one allele for a given trait is dominant. When both dominant alleles are inherited together, they fail to completely mask each other, so the resulting phenotype is one of "blending" the two characteristics.
One example of this is the AB blood type in people, in which both alleles A and B are codominant. If an A allele is inherited from one parent and a B allele is inherited from one parent then the offspring will have type AB blood (combination of the two)
Incomplete Dominance. Try this Punnett Square:
ex: snapdragon flowers can come in Red (allele R) or White (allele R'),both alleles are dominant.
RR= red flowers, R'R' = white flowers, so...
RR' = pink flowers (a combination of the two)
sample problem: What would be the probable flower color if you were to cross two pink snapdragons?
see page 184 in your text for explanation
do homework problems as practice! FYI: frizzled chicken
Dihybrid Cross- when two pairs of traits are considered in a cross
(review Mendel's Laws)
wrinkled-green producing plant crossed with a round, yellow (heterozygous) producing plant
if wrinkled and green are recessive alleles, then:
P (parents) genotypes are rryy and RrYy
Find all RrYy combinations possible for both parents
potential gametes: RY, Ry, rY, ry, etc.
9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green
Punnett squares and pea crosses (dihybrid example)
explanation and examples given on pages 185-186 in your textbook.
Background: Each gene serves as a recipe for building a protein molecule. When a particular protein is needed by the cell, the corresponding gene, made of DNA, is turned "on," or transcribed into a messenger RNA, which then carries the "protein recipe" to the protein-making machinery of the cell.
- Concept of "genes" -vs- "junk" sequences. See Chromosome 11 Flyover animation. (introns, exons, pseudogenes, transposons, etc)
- The activation of a gene results in transcription (mRNA made) which in turn results in the formation of a protein
- Not all genes are active in all cells
- Not all genes in a given cell are activated all the time
- There MUST be some way to control when a gene is turned "on" or "off"
As it turns out, chromosomes are really made up of genes and their ON and OFF switches ("regulatory genes")
"ON" = transcription and protein formation, "OFF" = not transcribed, no protein made
I. Prokaryotes (ex: bacteria)
Much less DNA (than eukaryotes, like humans) so much easier to study
- regulator gene- codes for the repressor
- promotor gene- attachment for polymerase enzyme
- operator gene- attachment for repressor
- structural genes- code for the different proteins the cell needs to make
When the RNA polymerase enzyme is not blocked by the repressor (genes are "ON") it will move along the structural genes causing them to be transcribed into mRNA; this results in the enzyme being made ("expressed").
When the repressor molecule is on the operator, transcription is "blocked", so no enzyme is made. In this case, the presence of lactose "induces" (turns "ON") transcription by essentially removing the repressor from the operator.
Try these tutorials, for further explanation:
- The Tryptophan Repressor (example of a gene that is turned "off" by presence of tryp)
- Combination of Switches - the Lac Operon
- Operon animated explanation
- lac operon movie (avi) 3:24
A. Gene expression
- Chromosome structure: chromatin (DNA helices) are wrapped around a central histone protein core.
- "nucleosomes": DNA wrapped around histones (proteins); forms beadlike loops in the chromatin.
- "heterochromatin": tightly coiled DNA; contains inactive genes
- "euchromatin": uncoiled DNA, "active genes" that are being transcribed image comparison
B. Enhancer Control (how eukaryote genes are transcribed)
"Enhancer" enables transcription of eukaryotic genes into mRNA, and then protein is formed
C. mRNA Cleavage (cutting and splicing only the necessary info together).
Pre-RNA (initial transcript) contains useful information - coding for protein- interspersed with some "junk" sequences. It must be modified before the ribosome can make the protein it calls for.
- Introns- inert DNA segments
- Exons- codons for protein synthesis
Modification of mRNA - prokaryotes -vs- eukaryotes:http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter15/animations.html#
short movie of mRNA editing (introns/exons)
III. Genes also determine how the body takes shape (learn.genetics.utah link)
"Morphogenesis" (from the Greek morphê "shape", and genesis "creation", literally, "beginning of the shape"), is the biological process that causes an organism to develop its shape. This generally begins to take place early in embryo development, but can also take place in adult organisms.
A. Embryo Development
All multicellular, sexually reproducing organisms start as a zygote (single diploid cell), to a morula (ball of mitotically dividing, identical cells) which then blastula (ball of cells hollows out, cavity forms inside)-->cell differentiation-->gastrula-->etc. early stages ; later stages
B. Homeotic Genes: are "master genes" that shape embryos. They are regulatory genes that determine where certain anatomical structures (such as appendages) develop. Homeobox: The specific DNA sequence in a homeotic gene.
- These "master genes" are conserved from flies to mice to humans (determine location of body parts in human embryos as well).
- Can even be found in fungi and plants (control flower development)
- Very well-studied in fruit flies (located on the 3rd chromosome)
- "Antennapedia" is a hox gene mutation first discovered in Drosophila which controls the placement of legs. Scientists can induce mutation in this, causing legs to grow in the place where antennae are normally found. image
- Also can manipulate the pbx (post-bithorax) and bx (bithorax) genes to this effect: image
- Check out the fly eye mutation picture on the introductory page of the chapter.
- Proto-oncogenes are regulatory genes control how large and how quickly cells grow, and ensure that the steps of mitosis are followed correctly. A mutation in a proto-oncogene can change it into an oncogene, which allows unchecked cell proliferation.
- Tumor-suppressor genes code for proteins that prevent excessive cell division. Damage to these genes leads to increased cell division, which can lead to a "blob" of extra cells (tumor).
Tumors: abnormal mass of cells that results from uncontrolled cell division.
- benign: non-spreading, contained
- malignant: spreads to other locations (metastatic)
Other forms of cancer have been found to be caused by genes which are passed through families. Examples?
Other types of cancer can be triggered/caused by viruses. Examples?
Most cancers, however, seem to be caused by random mutations, enhanced by exposure to mutagenic agents.
Kinds of cancer:
- Carcinomas: grow in the skin and body linings. ex: skin, lung, breast cancer
- Sarcomas: grow in muscle or bone
- Lymphomas: solid tumors that grow in tissues that form blood cells
- Leukemia: abnormal growth of white blood cells
Lab report Mitosis in Cancer Cells
"Inheritance Patterns and Human Genetics" (Ch. 12)
mid-1800’s Gregor Mendel - Laws of Inheritance; identified "factors" as hereditary information passed from parent to offspring.
1878- Walther Flemming - stained & identified chromosomes in the nucleus of cells; early observer of mitosis.
1902 Walter Sutton- tied Flemming's and Mendel's discoveries together into the "Chromosomal Theory of Heredity"
- chromosomes are the carriers of traits
- each chromosome carries many traits
1905 E.B Wilson - American cell biologist who1st determined that sex chromosomes (XX, XY system) are different from autosomes
REVIEW: In humans: total 23 pairs of chromosomes (homologous: inherit 1 from each parent)
- 1 pair of sex chromosomes XX or XY
- your 22 other pairs are called autosomes, body chromosomes that carry most of your traits
All the chromosomes of an individual cell can be visualized with a karyotype.
Sex is determined by the XX or XY combination (you get one from each parent). In males, the Y chromosome has special Sex-determining Region Y (SRY) genes that cause the embryonic gonads to develop into testes.
Thomas Hunt Morgan- American geneticist, won Nobel Prize 1933, discovered that some phenotypes are linked to mutations on the sex chromosomes, rather than autosomal.
Worked primarily with Drosophila melanogaster
- small, easy to keep
- produced new generation every 10-15 days
- each lays >100 eggs
- have only 8 chromosomes
X= may carry a recessive gene
Y = carries no genes; a"blank" (for our purposes)
Three examples in humans:
X= normal (dominant); Xc = recessive colorblindness mutation on the X chromosome
Hemophilia 1 in 7,500 males; 1 in 25,000,000 females (stats from http://www.ikm.jmu.edu/Buttsjl/ISAT493/Hemophilia/hemophiliaincidence.html)
X = normal (dominant) recessive mutation = Xh
X = normal (dominant) recessive mutation = Xd
Usually coded by an autosomal gene rather than a sex chromosome, so may be inherited by either sex, but presence of male or female hormones influences expression of the characteristic; ex: baldness, osteoporosis
Man: B'B' = bald, BB'= bald, BB = not bald
"The Basis of Heredity: Mutations" video (5:28)
- happens randomly every few thousand cell divisions
- can be increased by exposure to mutagens like chemicals or radiation
- can be in somatic cells or in germ cells (gametes)
- can be POSITIVE, NEGATIVE, or NEUTRAL(silent)
- are the "raw material" for evolution by natural selection
I. Gene Mutations
A random, unexpected change in a gene, generally passed on to offspring; caused by a mistake in replicating DNA --> DNA or transcribing DNA -->mRNA.
"Point mutation" can be caused by single nucleotide substitution. video (1:20)
Substitution mutations example
- Check out sickle cell anemia
normal hemoglobin gene = HbA
mutated hemoglobin gene = HbS
You inherit a hemoglobin gene copy from each parent, so possible genotypes are:
normal phenotype = HbAHbA
normal phenotype = HbAHbS (carrier of trait; few if any symptoms)
sickle cell disease = HbSHbS
Check out how a point mutation in HFE gene sequence leads to inherited disease: Hemochromatosis (interactive)
- If a gene produces proteins involved in controlling the cell's growth cycle, and this gene is affected by a chromosome rearrangement, uncontrolled cell growth (CANCER) could result.
- Third-base substitutions are often "silent". WHY? (see chart)
Insertions or deletions of nucleotide bases can cause even more serious problems: called a "Frameshift mutation": insertion or deletion of a single base can throw off "reading frame" for amino acid coding. This most often renders the (coded) protein nonfunctional. example here
gene mutation types tutorial, with examples
II. Chromosome Mutations
- Generally are more drastic than gene mutations
- During Mitosis or Meiosis, chromosomes may break and fragments can be lost or misplaced.
- Often lethal.
- animation of types of chromosomal mutations here
You can diagnose gross (large) chromosomal problems prenatally using "genetic screening" through a karyotype.
What to look for: chromosomal breakage, deletions, translocation
Major chromosomal mutations: "aneuploidy" (too many or too few entire chromosomes) are caused by Nondisjunction:
- In humans: errors in meiosis can leads to gametes: 22 (n-1) or 24 (n+1)
- Due to failure of parental chromosomes to separate (halve) correctly during meiotic formation of sperm and egg cells
- This can produce an abnormal sex cell in meiosis which, if fertilized, will produce an offspring with too many (or too few) chromosomes "Nondisjunction disorder" aka "aneuploidy"
- Animated example of how nondisjunction occurs
This can result in several problematic conditions:
- Down Syndrome (Trisomy 21)
- Edwards Syndrome (Trisomy 18)
- Patau Syndrome (Trisomy 13)
- certain types of cancer have been associated with certain nondisjunctions
sex chromosome aneuploidy:
**To view more about the characteristics of these disorders, click this links above, or watch this powerpoint
Polyploidy - inheriting a complete extra set of chromosomes from a gamete (due to failure to separate after replication)
- 3n, 4n, etc.
- More common in plants. For example
- Polyploidy can also be induced in the plant breeding laboratory by treating dividing cells with colchicine (an alkaloid of the meadow saffron). This drug disrupts microtubules and thus prevents the formation of a spindle. Consequently, the duplicated chromosomes fail to separate in mitosis. Onion cells exposed to colchicine for several days may have over 1000 chromosomes inside.
- Rarely see polyploidy in animals. For example
How do we locate where exactly a gene is on a chromosome? We can monitor how often they CROSS OVER (alleles on chromosomes become rearranged during meiosis. picture)
The probability of crossing over between genes on a chromosome is dependent on the distances between the genes.
This shouldn't surprise you because the greater the distance between two genes, the greater the chance a break will occur.
GENE LINKAGE: groups of genes located on the same chromosome that tend to be inherited together because the DNA sequence containing the genes is passed along as a unit during meiosis.
The closer that genes reside on a particular chromosome, the higher the probability that they will be inherited as a unit, since crossing over between two linked genes is not as common.
ex:"Which of Mendel's laws does this contradict?"
"Chromosome Mapping" is now possible. The crossover frequency (%) is directly related to a gene's position on the chromosome.
A linkage map portrays the sequence of genes along a chromosome, but it does not give the precise location of the genes. To determine the distance between two genes, the recombination frequency is used (1% = 1 map unit (m.u.))
See textbook page 238 for pictures and further explanation
Sample problem: the relative abundance of four genes on a chromosome can be mapped from the following data on crossover frequencies:
|GENES||Frequency of Crossover|
|B and D||5%|
|C and A||15%|
|A and B||30%|
|C and B||45%|
|C and D||50%|
Which of the following represents the relative positions of the four genes on the chromosome?
a. ABCD b. ADCB c. CABD d. CBAD e. DBCA
More Human Genetics
Studying humans is often difficult
- long generational interval
- lots of genes
- ethical concerns
- control experiment
Population Sampling - random; use a small sample to statistically analyze population as a whole; used to determine the frequency of genetic traits or the frequency of alleles in the population.
- gene pool- all of the genes in a given population
- studying one generation's gene frequencies can often predict the next generation's
- gene frequencies can be kept fairly constant, from one generation to the next, when the following conditions are met:
- large populations
- random mating
- no migration
- no mutations
- no selection of alleles
What are some ways to manipulate (change) gene frequencies from one generation to the next?
- controlled/selective breeding
- nonrandom mating
- environmental influence
- there are some isolated gene pools within larger populations that have unusual allele frequencies
examples of genes that are more prevalent in American subpopulations:
- Tay Sachs disease (in descendants of Eastern European Jews) info images
- Sickle Cell Anemia (in descendants of African origin) info images
- Polydactyly, dwarfism (in Amish) info image
Twin Studies "Nature -vs- Nurture" question:
- How much of what you are is due to, your genes? How much is due to your environment?
- Some genetic traits are generally unaffected by the environment: blood type, eye color
- Some genetic traits have a large environmental component ("multifactorial"): height, weight, IQ
- fraternal -vs- identical twins (studies)
- recessive: most genetic disease (see this list from Wikipedia for several examples)
- dominant (ex: Huntington disease, Dwarfism)
- Dd or DD = affected, dd = normal
- co-dominant (ex: sickle cell anemia)
- AA (normal), AA' (ok), or A'A' (bad)
Polygenic traits: characteristics that are coded for by more than one gene
Multiple Allele Crosses: when more than two alleles code for a trait
- IA = type A allele
- IB = type B allele
- i = type O allele (recessive)
IAIB = ? (codominance) IAi=? IBi = ?
Should be able to do a Punnett square to predict the outcome of blood types!
Some human genetic traits:
|Single allele, dominant||Single allele, recessive||Sex-linked traits||Polygenic traits||Multiple alleles|
|Huntington disease||Albinism||Color-blindness||Skin, hair, and eye color||ABO Blood type|
|Polydactyly (extra digits)||Cystic fibrosis||Hemophilia||Foot size|
|Cataracts||Phenylketonuria (PKU)||Muscular dystrophy||Nose length|
|Achondroplasia (dwarfism)||Hereditary deafness||Ichthyosis simplex (scaly skin)||Height|
some more inherited human disorders
Chapter 13 DNA Technology:"APPLIED GENETICS"
- te, chniques have been used for centuries
- makes it possible to alter the heredity of organisms in order to adapt them to particular environmental conditions and improve their traits to make them more useful to us (humans)
I. CLASSICAL APPLIED GENETICS
Mass Selection: the process of selecting a few parents (plants or animals) from a la, rge number of individuals; few selected for breeding on the basis of their desirable characteristics
Inbreeding: involves the mating of plants or animals that have the same or similar genetic makeups; used to preserve a particular trait in a plant, or animalstrain.
&n, bsp; examples:
Hybridization: the crossing of two different, but related strains of plants or animals in order to combine their different desirable traits in their offspring; matings between two genetically different individuals
Polyploidy: condition in which more than the usual diploid # of chromosomes are present in an organism; not uncommon in plants; can be induced by treatment with colchicine
II. Molecular Applied Genetics...uses genetic engineering to artificially alter the genetic makeup of organisms
Restriction Enzymes (pg. 257, top)
bacterial enzymes used to cut DNA between specific base sequences
for example, this enzyme cuts only between TCGAA sequences:
enzymes that act like molecular "glue" to splice genes together
Cloning a gene
1. isolating a gene
2. using bacterial plasmids to replicate it, makes multiple copies of the "gene of interest", for insertion into other cells/organisms
Gene Splicing (engineering): identifying and cutting out a desired gene from one organism and splicing it into the DNA of another, using restriction enzymes.
- first identify the chromosome and mark the gene you want
- then use "restriction enzymes" to cut between specific bases in the DNA
- then, insert the gene into a bacterium (using more enzymes as "scissors" and "glue")
What are some of the APPLICATIONS of DNA technology?
example: human insulin gene spliced into a microorganism (see pg. 259)
- Bacteria have a little "wheels" of DNA, called PLASMIDS, that are easily spliced with new genes.
- Because bacteria replicate rapidly in lab conditions, they can be used to easily create multiple copies of the inserted genes = "cloning vectors"
can be inserted into bacterial cells which will then manufacture the insulin for use in humans
Medical Applications: "GENE THERAPY"
- can insert genes into human cells that lack them (ex: bone marrow stem cells)
- can use viruses as "vectors" to carry genes and "infect" cells with them
- see Fig. 13-11 on pg. 267 CFTR gene therapy
DNA Technology Techniques:
PCR (Polymerase Chain Reaction): a technique for rapidly producing millions of copies of a particular stretch of DNA. In this case, PCR is used to amplify the region of DNA containing a gene of interest (ex: Huntington's gene).
Since, often, only small amounts of DNA are found at crime scenes, PCR is often done first so that enough copies of the DNA are available to do analyses.
DNA fingerprinting (pp. 256-258)
- isolate DNA from cells
- "chop it up" using restriction enzymes
- run the DNA fragments through an electrical field to separate them into bands
What is the Accuracy? since every individual is genetically unique, to some extent, this is an excellent way to separate individuals from one another (based on gene polymorphisms, VNTRs)
Can be used with confidence to identify (or exclude) individuals in criminal investigations. Odds are about 1 in a billion that another person has the same profile as you! (pg. 258)
- Try your hand at DNA Fingerprinting to solve a crime, HERE (It Takes A Licking - NOVA)
The Human Genome Project: begun in 1990, the U.S. Human Genome Project has been an ongoing effort coordinated by the U.S. Department of Energy and the National Institutes of Health. The project originally was planned to last 15 years, but rapid technological advances have accelerated the expected completion date.
Two private companies actually completed the project in 2003.
Project goal: identify all the estimated 30,000+ genes in human DNA, determine the sequences of the 3 billion chemical bases that make up human DNA, store this information in databases, develop tools for data analysis, and address the ethical, legal, and social issues that may arise from the project.
Check out how the genome was mapped here
Genetically Modified (GM) Plants: A transgenic crop plant contains a gene or genes which have been artificially inserted instead of the plant acquiring them through pollination. The inserted gene sequence (known as the transgene) may come from another unrelated plant, or from a completely different species: transgenic Bt corn, for example, which produces its own insecticide, contains a gene from a bacterium.
Transgenic Animals: can be used for medical research ("knockout mice") or to produce human proteins which can be harvested for our use. 2011news: Human Breast Milk from a Cow