Classical (Mendelian) Genetics

I.
Gregor Mendel
A.
Mendelís Approach
1.
Isolate and study one characteristic at a time, making sure to begin with true-breeding strains.
2.
Follow breeding schemes for more than one generation.
3.
Analyse data using statistical methods.
B.
Mendelís Discoveries
1.
Heredity is binary: Each trait is controlled by two factors.
2.†
Hereditary factors are particulate (Law of Segregation), not fluid.
3.
In the hybrid, one factor may completely hide the presence of the partner factor (Principle of (complete) Dominance).†
4.
Traits are inherited independently of each other (Law of Independent Assortment).
C.
Modern terminology
1.
The factors which control heredity are now called genes, and the different versions of genes are called alleles.
2.
A pure or true breeding organism is a homozygote; a hybrid is a heterozygote. The first is homozygous, the second heterozygous.

II.
Lynnís Rules for Pedigree Analysis
A.
Rule #1: Every gamete contains exactly one allele for every gene.† [Exception:† sex linked genes in sperm]
B.
Rule #2: Any individual who shows the recessive phenotype must be homozygous recessive.
C.
Rule #3: Any individual with a homozygous recessive offspring must possess at least one recessive allele.
D.
Rule #4: Any individual with a homozygous recessive parent must possess at least one recessive allele.
E.
Rule #5: Donít guess.

III.
The Chromosomal Connection
A.
Genes are part of chromosomes; a chromosome generally carries thousands of different genes.
B.
Chromosome number counts†
1.
Ploidy refers to the number of chromosome sets in the nucleus of a cell.
a.
A haploid nucleus has a single set of chromosomes. Thus, it has one of each kind of chromosome.
b.
A diploid nucleus has two sets of chromosomes. Thus it has two of each kind of chromosome.
c.
Triploid: three sets of chromosomes; tetraploid: four sets, etc.
d.
The somatic (body) cells of animals are almost always diploid; gametes are almost always haploid.
e.
Plants are far more tolerant of multiple chromosome sets than animals. In fact, increased numbers of chromosome sets is one mode by which plants can evolve. For example, wheat is a hexaploid. It is a natural hybrid among three different species of grasses, and each of its nuclei contain two sets of chromosomes frmo each of those ancestral species, for a total of six sets.
2.
chromosomes which are the same size and shape, and which have identical gene maps are homologous. The two sets of chromosomes in a diploid nucleus are homologous to each other; the chromosomes of members of the same species are homologous to each other.
C.
A meticulously created image in which chromosomes are photographed, lined up from largest to smallest, paired with their homologous partners, then glued down to a piece of paper is called a karyotype.
D.
Many kinds of animals use chromosomes to determine gender. However, there are many gender determining systems which don't involve chromosomes, or utilize them in a manner different from the XX/XY system that most people know.
1.
Mammals use a system in which gender is determined by the action of a gene on a particular chromosome called the Y chromosome. A mammal with a Y chromosome is male; one without is female. To a large extent, it doesn't matter how many X chromosomes a mammal has (with respect to gender).
2.
That famous fruit fly so beloved of geneticists, Drosophila, has a system which looks like the mammalian system, but actually works through a different determination method. In fruit flies, what matters is the balance between the number of X chromosomes and the number of sets of autosomes (all of the chromosomes other than the sex chromosomes). It doesn't matter if there is a Y chromosome present or not--if a fly has the same number of X chromosomes as it has sets of autosomes (or more) it will be a female. If it has 1/2 as many X chromosomes as it has sets of autosomes, it will be male whether it has a Y or not.
3.
Grasshoppers have taken the Drosophila system to the extreme, and simply done away with the Y chromosome altogether. Male grasshoppers simply have one X chromosome with no partner, and have one fewer chromosomes than female grasshoppers have.
4.
Birds use a system which essentially works in the opposite way as the mammalian system. Their sex chromosomes are called the Z and the W. A male bird has two Z's, a female has one Z and one W.
5.
Many reptiles determine sex by a system which has nothing to do with chromosomes at all. The gender of the baby that hatches out of an egg is determined by the temperature at which the egg incubates. The warmer ones hatch males, the cooler ones females.
6.
Honey bees use a system which seems very strange to us. Female honey bees are diploid; males are haploid. They develop from unfertilized eggs.

IV.
Mitosis and Meiosis
A.
These two processes function to pass chromosomes from one cellular generation to the next in a very carefully controlled manner.
B.
Mitosis and Meiosis are both correctly described as nuclear division; they are never correctly called cell division, or any kind of reproduction. It is possible (and often quite normal) for nuclei to divide when cells don't. And organisms reproduce; nuclei and cells divide.
C.
Mitosis
1.
Mitosis is the division of a nucleus to produce two genetically identical daughter nuclei.
2.
Mitosis is utilized for any function which requires the production of more cells with identical genetic information. These processes include the vase majority of cell production during the growth of an organism, the cell division needed for healing and repair, and the division of nuclei when an organism is in the process of asexual reproduction. Note: Mitosis is not asexual reproduction, nor can it be called asexual cell (or even nuclear) division.
3.
Because the vast majority of the cells in a multicellular organism were produced by mitotic cell division, those cells all have identical nuclei. They obviously don't all look or function alike. Cells mature through a process called differentiation in which select sets of genes are turned on and off, resulting in changes in the structure and function of the cell.
D.
Meiosis
1.
Meiosis is the division of one diploid (usually) nucleus to produce four haploid (usually) nuclei, all genetically different. Though the vast majority of the time the chromosome number reduction is from diploid to haploid, in some cases it may be from, say, hexaploid (eg., wheat) to triploid.
2.
Meiosis performs a key task necessary in a sexual life cycle. Since fertilization (which is the actual sexual event in the life cycle) automatically doubles chromosome number by combining the chromosomes of an egg and a sperm, it is essential that some event occur somewhere in the life cycle which reduced the chromosome number to compensate.
3.
Though Meiosis is part of a sexual life cycle, it is not ever correctly described as, for instance, "sexual cell division," and certainly not as "sexual reproduction." It is the life cycle, and specifically the fertilization event, which constitute sexual activity, not Meiosis.
4.
In animal life cycles, the meiotic cell division in the life cycle immediately precedes the development of gametes (eggs and sperm). However, this need not at all be the case. Plants have a somewhat different sexual life cycle from animals which includes all of the same events, including Meiosis, production of gametes, and fertilization, but also includes an additional phase between Meiosis and gamete production.
E.
There are three differences between what Mitosis accomplishes and what Meiosis accomplishes.
1.
Mitosis divides one nucleus into two; Meiosis divides one nucleus into four.
2.
Mitosis conserves chromosome number; Meiosis reduces it in half (usually from diploid to haploid).
3.
Mitosis produces genetically identical daughter nuclei; Meiosis produces genetically different daughter nuclei.
F.
Errors in nuclear division can produce chromosome anomalies.
1.
Nuclei whose chromosomes do not form normal sets (eg, which have extra or missing chromosomes in one or more of the chromosome sets) are aneuploid.
a.
Aneuploidies typically result from nondysjunction in either Meiosis I or Meiosis II.
b.
If a nucleus which should be diploid has three of a chromosome instead of the normal two, that nucleus is trisomic. For example, if the nucleus of a human cell has three of chromosome 18, that would be trisomy 18. This term is also used for an organism, all of whose cells are trisomic. Trisomy 21 can refer to a human, all of whose cells have three twenty-first chromosomes instead of the expected two.
c.
If a nucleus which should be diploid has only one of a chromosome in stead fo the normal two, that nucleus is monosomic. An individual may be described as monosomic if all (or most) of the cells in that individual are monosomic. For example, Turner's Syndrome female humans are monosomic for the X chromosome.
d.
Other things being equal, it is significantly worse to be missing chromosome material than to have extra chromosome materials. Of course, the specific genes on the extra or missing chromosome material also impact on how serious the effects of the anomaly will be.
2.
A nucleus which has extra sets of chromosomes (like the wheat mentioned above) is polyploid.
a.
Polyploidy typically results from fertilization inv0lving gametes with unreduced chromosome number. In other words, an error in chromosome reduction during Meiosis produces a gamete which still has the diploid number of chromosome sets, which then participates in fertilization with a haploid gamete.
b.
An autopolyploid has more than two sets of chromosomes from the same species. In other words, it has more than two homologous sets of chromosomes. Commercially grown bananas are autotriploids; they have three sets of banana chromosomes. Autopolyploids frequently have difficulty performing Meiosis because the pairing mechanism in Prophase I requires one-on-one pairing between two partners, and having more than two homologues in the same nucleus creates confused pairing.
c.
An allopolyploid has chromosomes from more than one species. Wheat is an allohexaploid. It has two each of the chromosome sets from three different species of grasses, so each nucleus has six sets of chromosomes, but each chromosome has only one homologous partner in the nucleus. For this reason, allopolyploids are often perfectly fertile, as wheat obviously is. Allopolyploids are generally formed by an accidental fertilization between two different, closely related species (producing an offspring which is technically diploid, but whose chromosomes don't match--a mule is an example of this situation). In plants, it is frequently possible for the plant to reproduce asexually, so the inability to perform Meiosis may not be a problem which prevents survival and reproduction. (This is why commercial bananas can reproduct successfully, despite being unable to do Meiosis.) Our inter-species hybrid can thus generally reproduce and thrive. Eventually, an accidental chromosome doubling event can double both chromosome sets, producing a plant which is technically tetraploid (having four sets of chromosomes) but functionally diploid (as each chromosome has only one homologous partner in the nucleus). This restores the ability to reproduce sexually, and also creates a brand new species. Clearly, this happens. It's happened twice in the natural history of Triticum (wheat).
3.
Sometimes chromosomes lose segments, or acquire extra copies of segments. These are called insertions and deletions, or duplications and deficiencies. These generally arise due to uneven crossovers during Prophase I of Meiosis. They can result from crossing over in inversion heterozygotes.
4.
Occasionally, a segment of a chromosome will break free and accidentally reattach with its ends switched around. This reversed segment of the chromosome is an inversion.
a.
If the cell is an inversion homozygote, which means that both chromosomes of a homologous pair carry the same inversion, this causes no problems for the organism (though it might lead to fertility problems with offspring, which could very easily be inversion heterozygotes).
b.
If a cell has one chromosome of a pair which carries an inversion, but the partner doesn't, the cell is an inversion heterozygote. Inversion heterozygotes are, themselves, perfectly healthy, but in Meiosis the inversion can create several problems.
i.
In Prophase I of Meiosis, chromosomes synapse on a gene-by-gene basis. So in the region of the inversion, when the homologous chromosomes pair they create an inversion loop as the frontward/backward segments attempt to pair normally. This isn't, in itself, a problem, but if a crossover occurs within the inversion loop, it will lead to duplication and deficiency.
ii.
If the inverted region does not include the centromere of the chromosome, and a crossover occurs within the inverted region, it will lead to one dicentric chromatid (a chromatid which has two centromeres) and one acentric chromatid (a chromatid which has no centromere). As the pull of spindle fibers on the centromeres is what moves chromosomes around during Meiosis and Mitotis, this typically leads to disaster.
5.
Sometimes, a segment of one chromosome gets accidentally broken off and attached to a different chromosome. This is a translocation.
a.
If no genes are lost or damaged by the translocation, and all genes are present in the correct quantity (generally two), the result is a balanced translocation, which causes no problems for the individual possessing the translocation, though it may cause problems in gamete production and for the offspring.
b.
If the translocation involves trading pieces of both chromosomes involved, it's called a reciprocal translocation.
c.
As with inversions, translocations may be homozygous or heterozygous. A translocation homozygote has no problems; he or she simply has an unusual arrangement of genes on his or her chromosomes, but everything works perfectly.
d.
A translocation heterozygote has problems in synapsis, just as the inversion heterozygote does, because the chromosomes try to pair gene-to-gene, and the genes are located on different chromosomes in the two homologous pairs. Again, crossing over in the wrong place can lead to duplication and deficiencies, and to dicentric and acentric chromosomes. Note that an individual can be a translocation heterozygote and still have a perfectly balanced gene complement.
e.
Even if no unfortunate crossing over occurs, the outcome of a fertilization between someone carrying a balanced translocation and someone with the more usual chromosome complement can cause problems for the offspring. The zygote will receive a normally arranged set of chromosomes from one gamete, but may receive a translocated chromosome (but not its reciprocal partner) from the other. A rare version of Down's Syndrome (which generally results from trisomy of the twenty-first chromosome) results from this sort of problem. The zygote receives two normal twenty-first chromosomes, plus one normal fourteenth chromosome and one fourteenth chromosome which is carrying a translocated copy of most of the twenty-first chromosome. The result is a genome which has the appropriate number of chromosomes, but in which one of the fourteenth chromosomes also carries a copy of the twenty-first chromosome. Thus the child functionally has three copies of chromosome twenty-one, and all of the normal characteristics of Down's Syndrome.
6.
Note that chromosome rearrangements like inversions and translocations have important impact on speciation--the division of one species into two. What distinguishes one species from another is the inability to reproduce and produce fertile offspring, and if chromosome rearrangements arise and become "fixed" within a section of a species, that subgroup can easily become unable to reproduce with the original, parent species. This is one of the things that happens when segments of a species become isolated from other segments. Comparing the chromosomes of closely related species shows us that this is a very significant way in which they differ from each other. This is why, for example, a horse can breed with a donkey (different, but closely related species) and produce a completely healthy, even robust, hybrid: a mule. Mules are strong and healthy because the chromosomes of the donkey and those of the horse carry very complementary kinds of genes, and the two sets of genetic influences interact very well, with little missing. However, the mule is sterile, because his horse chromosomes and his donkey chromosomes have significant differences in arrangement (inversions and translocations) and thus are unable to complete Meiosis.

V.
Some concepts you should understand:
A.
In genetics, there are two different ways to describe individuals.
1.
The genotype is a description of the specific alleles carried by the organism, with respect to the particular genes being considered. Genotypes are typically a cluster of letter symbols, such as BbCCDd.
2.
The phenotype is the actual description of the characteristics we see in the organism. For instance, "brown fur," or "green eyes" could be phenotypes. Note that phenotypes are not completely determined by genotypes; environment also has an impact, sometimes a very significant one.
B.
The terms Pure Breeding and True Breeding are euphemisms for homozygous. It's a breeder's term which refers to an individual which, when paired with an appropriate partner, always produces offspring with the same characteristics of the parent.
C.
Another breeder's term is hybrid. It refers to an individual which was produced by crossing two different pure-breeding parents. This term is a euphemism for heterozygous.
D.
The Wild Type version of a trait is that version which is overwhelmingly most common in nature. Wild type can change if the general character of the species changes. For example, among our distant ancestors the wild type eye color would certainly have been brown. However, the modern human species has no wild type eye color. All human beings are members of the same species, and there is no overwhelmingly most common eye color.
E.
An individual whose two alleles for a specific traits are identical is homozygous--a homozygote; one who has two different alleles for a specific trait is heterozygous--a heterozygote. If an individual has only one allele for a trait (such as for sex linked genes in males), that individual is hemizygous--a hemozygote.
F.
The gender which has two identical sex chromosomes is the homogametic gender; the gender with two different sex chromosomes is the heterogametic gender. In mammals, females are homogametic and males are heterogametic; in birds it's the other way around. The terms refer to the fact that, with respect to sex chromosomes, mammalian females produce gametes which are all the same, while males produce gametes of two different types.
G.
Despite what most beginning biology students are taught, there are actually several different kinds of dominance relationships. Dominance is always defined with respect to the phenotype of the heterozygote.
1.
If two alleles have a complete dominance relationship, the phenotype of the heterozygote will be indistinguishable from the phenotype of one of the homozygotes. The allele which is expressed in the heterozygote is called the dominant allele; the allele which is hidden in the heterozygote is called the recessive allele. Note that dominance is a matter of biochemistry, not frequency. The most frequent phenotype does not necessarily represent the dominant allele.
2.
There need not actually be a dominant allele. There are at least two situations in which neither allele of a pair would be dominant.
a.
If the phenotype of the heterozygote is intermediate between the phenotype of the two homozygotes, the alleles share an incomplete dominance relationship. And example of this might be a plant with two alleles for flower color, one of which produces red flowers in a homozygote, while the other produces white flowers in its homozygote. If the heterozygote produces pink flowers, the two alleles show incomplete dominance.
b.
If the heterozygote expresses both allelic traits, the relationship between the alleles is co-dominance. For example, in human blood types, an influential gene has three alleles, typically called the A, B, and O alleles. (NOTE: The correct symbols for these alleles would not be A, B and O, as all alleles of a single gene need to be represented by the same symbol. The symbol for the alleles of this gene is the letter "I," with superscripts for the different alleles.) Among these three alleles, the O allele is recessive to both A and B. But the A and B alleles show co-dominance. Their heterozygote has blood type AB, which is Type A and Type B at the same time.
c.
In some cases, a particular combination of alleles produces a lethal effect. Because this situation initially looks like a case of complete dominance, it has come to be called pseudodominance. For example, in gerbils there is a gene with two alleles, W and w. A Ww (heterozygote) gerbil has a white-spotting pattern in its fur color; a ww (homozygous little-w) gerbil has solid colored fur. The WW (homozygous big-W) condition is lethal--gerbils that receive this genotype die as fetuses, and are never seen among living gerbils.
H.
The location of a gene on the chromosomes of a species is its locus [plural: loci]. Sometimes this term is actually used as a euphemism for "gene," as in, "The Huntington's locus is on the fourth chromosome."
I.
A pedigree is a charted family history. In genetics, this is a multi-layered chart showing males as little squares, females as little circles, and those of unknown gender is little diamonds. Horizontal lines join parental couples; siblings are linked by hanging together underneath a single line. These can be very useful for determining the inheritance patterns of genetic factors.
J.
If two genes have their loci on the same chromosome, they are described as linked. When Mendel studied the independence of different hereditary factors, he was apparently very lucky in that he didn't choose to examine any genes which were linked closely enough to interfere with the statistical independence of their inheritance patterns. Of course, two genes which are physically linked together will not be inherited independently of each other. They will tend to stick together unless separated by crossing over. Since the further apart two linked genes are, the more likely it is that at least one crossover will occur between their loci, calculating recombination frequency between linked genes can be used as a mapping tool. Two genes which are located so closely together that they are virtually never separated by crossing over are sometimes described as completely linked, though our modern understanding of crossing over tells us that it isn't possible for two loci to literally be inseparable.
K.
The proteinaceous structure that forms among the four chromatids of a synapsed pair of chromosomes during Prophase I is called the synaptinemal complex. It is very likely that the synaptinemal complex is responsible for at least some of the events that cause crossing over.
L.
The production of gametes (in animals, from the products of Meiosis) is called gametogenesis.
1.
Egg production is oogenesis. The cytokinesis accompanying Meiosis preceding egg production is typically very unequal, producing one very large offspring cell (fated to go through oogenesis) and three tiny polar bodies. The polar bodies are actually sacrifices for the sake of preserving the maximum amount of cytoplasm in the presumptive egg, thus reducing the amount of work necessary in oogenesis, as an egg is by quite a bit the largest uninucleate cell in the organism.
2.
Sperm production is spermatogenesis. Meiosis in males is accompanied by equal cytokinesis, so each Meiotic cell division produces four presumptive sperm. Spermatogenesis involves getting rid of the vast majority of the cytoplasm in each of these cells, packing the nucleus as compactly as possible, and constructing the flagellum of the sperm tail and the large mitochondrial "engine" to power it.
M.
As should be evident from earlier parts of this document, the number of each chromosome present in a nucleus (and thus in the cells of an individual) is vital. If the proper number of each chromosome is two, then if there are three of one of the chromosomes, it's disastrous for the cell and the organism. If there is only one when there should be two, that is an even worse problem. There are no known human monosomies which survive gestation--except one. And there's a very good reason for that one exception, which is related to a puzzle which should have occured to anyone reading this. If the number of any chromosome is very important, why is it that males have only one X chromosome and females have two? The genes on this chromosome don't have anything to do with the features of the two genders. They control things like blood clotting factors and color vision. And the Y chromosome doesn't duplicate these genes--males literally have only one copy, while females have two. This disparity is solved by something called dosage compensation. In mammalian cells, any X chromosome beyond one is condensed and inactivate, so the number of active X chromosomes in any cell is only one. So the cells of females have only one active X chromosome; the other is inactive and condensed into a relatively easily seen (with the appropriate cellular stains) blob called a Barr body. The only surviving human monosomy is a Turner female, who has a single X chromosome but no partnering chromosome. She survives, and is relatively normal, because in an XX female, one of those X's would be inactive in every cell anyway. Humans with extra X chromosomes also survive, and are relatively normal, because that X inactivation system converts all extra X chromosomes into Barr bodies. These would be Klinefelter males. Note that neither Turner females nor Klinefelter males are completely normal; those extra X chromosomes do have an impact. But it is far less than the impact of aneuploidy in a similarly sized autosome.