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COURSE CODE: AEB 212

COURSE TITLE:INTRODUCTION TO GENETICS AND CELL PHYSIOLOGY PART B

NUMBER OF UNITS: 2 Units

COURSE DURATION:Two hours per week

COURSE LECTURERS: MRS H.J.OZEMOKA

  1. Define and apply Mendel’s law of Independent Assortment
  2. Understand the concept behind linkages and recombination
  3. Discuss and analyze sex linked characters and their presentation
  4. Know the uses and application of sex liked characters.

COURSE DETAILS:

Week 3:Mendel’s Laws of inheritance

Week 4:Linkage and Recombination and possible examples

Week 5:Sex-linked inheritance, why sex

Week 6:Phylogenetic Inheritance, application in genetics

RESOURCES

• Lecturer’s Office Hours:

Mrs. H. J. Ozemoka

• Course lecture Notes: joy

• Assessments

• 2 assignments

• 1 test

• Practical Sessions (Assessments take 30% of final grade)

• Exams:

• Final, comprehensive (according to university schedule): ~ 70% of final grade

Assignments & Grading

• Academic Honesty: All practical sessions should be done independently, unlessexplicitly stated otherwise on the assignment handout.

• You may discuss general solution to practical examinations

• Presentations should be taken seriously; this is an integral part of group discussion and an opportunity for all students to interact efficiently.

• NO LATE HOMEWORKS ACCEPTED

• Turn in what you have at the time it’s due.

• All homeworks are due at the start of class.

• If you will be away, turn in the homework early.

PREAMBLE:

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked.

Introduction:

Genetic linkage is the most prominent exception to Gregor Mendel's Law of Independent Assortment. The first experiment to demonstrate linkage was carried out in 1905. At the time, the reason why certain traits tend to be inherited together was unknown. Later work revealed that genes are physical structures related by physical distance.

The typical unit of genetic linkage is the centimorgan (cM). A distance of 1 cM between two markers means that the markers are separated to different chromosomes on average once per 100 meioses.

Linkage map

A linkage map (also known as a genetic map) is a table for a species or experimental population that shows the position of its known genes or genetic markers relative to each other in terms of recombination frequency, rather than a specific physical distance along each chromosome. Linkage maps were first developed by Alfred Sturtevant, a student of Thomas Hunt Morgan

Thomas Hunt Morgan'sDrosophila melanogaster genetic linkage map.

This was the first successful gene mapping work and provides important evidence for the chromosome theory of inheritance. The map shows the relative positions of alleles on the second Drosophila chromosome. The distances between the genes (centimorgans) are equal to the percentages of chromosomal crossover events that occur between different alleles.

Uses of genetic map

Genetic maps help researchers to locate other markers, such as other genes by testing for genetic linkage of the already known markers.

Note: A genetic map is not a physical map (such as a radiation reduced hybrid map) or gene map.

Recombination frequency

Recombination frequency is a measure of genetic linkage and is used in the creation of a genetic linkage map. Recombination frequency (θ) is the frequency with which a single chromosomal crossover will take place between two genes during meiosis. A centimorgan (cM) is a unit that describes a recombination frequency of 1%. In this way we can measure the genetic distance between two loci, based upon their recombination frequency. This is a good estimate of the real distance. Double crossovers would turn into no recombination. In this case we cannot tell if crossovers took place. If the loci we're analysing are very close (less than 7 cM) a double crossover is very unlikely. When distances become higher, the likelihood of a double crossover increases. As the likelihood of a double crossover increases we systematically underestimate the genetic distance between two loci.

During meiosis, chromosomes assort randomly into gametes, such that the segregation of alleles of one gene is independent of alleles of another gene. This is stated in Mendel's Second Law and is known as the law of independent assortment. The law of independent assortment always holds true for genes that are located on different chromosomes, but for genes that are on the same chromosome, it does not always hold true.

As an example of independent assortment, consider the crossing of the pure-bred homozygote parental strain with genotypeAABB with a different pure-bred strain with genotype aabb. A and a and B and b represent the alleles of genes A and B. Crossing these homozygous parental strains will result in F1 generation offspring that are double heterozygotes with genotype AaBb. The F1 offspring AaBb produces gametes that are AB, Ab, aB, and ab with equal frequencies (25%) because the alleles of gene A assort independently of the alleles for gene B during meiosis. Note that 2 of the 4 gametes (50%)—Ab and aB—were not present in the parental generation. These gametes represent recombinant gametes. Recombinant gametes are those gametes that differ from both of the haploid gametes that made up the original diploid cell. In this example, the recombination frequency is 50% since 2 of the 4 gametes were recombinant gametes.

The recombination frequency will be 50% when two genes are located on different chromosomes or when they are widely separated on the same chromosome. This is a consequence of independent assortment.

When two genes are close together on the same chromosome, they do not assort independently and are said to be linked. Whereas genes located on different chromosomes assort independently and have a recombination frequency of 50%, linked genes have a recombination frequency that is less than 50%.

As an example of linkage, consider the classic experiment by William Bateson and Reginald Punnett.They were interested in trait inheritance in the sweet pea and were studying two genes—the gene for flower colour (P, purple, and p, red) and the gene affecting the shape of pollen grains (L, long, and l, round). They crossed the pure lines PPLL and ppll and then self-crossed the resulting PpLl lines. According to Mendelian genetics, the expected phenotypes would occur in a 9:3:3:1 ratio of PL:Pl:pL:pl. To their surprise, they observed an increased frequency of PL and pl and a decreased frequency of Pl and pL.

Bateson and Punnett experiment
Phenotype and genotype / Observed / Expected from 9:3:3:1 ratio
Purple, long (P_L_) / 284 / 216
Purple, round (P_ll) / 21 / 72
Red, long (ppL_) / 21 / 72
Red, round (ppll) / 55 / 24

Their experiment revealed linkage between the P and L alleles and the p and l alleles. The frequency of P occurring together with L and with p occurring together with l is greater than that of the recombinant Pl and pL. The recombination frequency is more difficult to compute in an F2 cross than a backcross,[3] but the lack of fit between observed and expected numbers of progeny in the above table indicate it is less than 50%.

The progeny in this case received two dominant alleles linked on one chromosome (referred to as coupling or cis arrangement). However, after crossover, some progeny could have received one parental chromosome with a dominant allele for one trait (e.g. Purple) linked to a recessive allele for a second trait (e.g. round) with the opposite being true for the other parental chromosome (e.g. red and Long). This is referred to as repulsion or a trans arrangement. The phenotype here would still be purple and long but a test cross of this individual with the recessive parent would produce progeny with much greater proportion of the two crossover phenotypes. While such a problem may not seem likely from this example, unfavourable repulsion linkages do appear when breeding for disease resistance in some crops.

The two possible arrangements, cis and trans, of alleles in a double heterozygote are referred to as gametic phases

Recombination and Linkage

Each human somatic cell contains two of each type of chromosome. One chromosome of each of the 23 pairs came from the mother and the other from the father. When gametes are produced (by meiosis), the paired homologous chromosomes separate so that each gamete contains only one of the pair of alleles for each trait.

Homologous chromosomes
separating in the production
of sex cells /

Which chromosome from each of the 23 homologous pairs of both parents is inherited is a matter of chance. There are 8,324,608 possible combinations of 23 chromosome pairs. As a result, two gametes virtually never have exactly the same combination of chromosomes. Each chromosome contains dozens to thousands of different genes. The total possible combination of alleles for those genes in humans is approximately 70,368,744,177,664. This is trillions of times more combinations than the number of people who have ever lived. This accounts for the fact that nearly everyone, except monozygotic twins, is genetically unique.

While homologous pairs of chromosomes are independently assorted in meiosis, the genes that they contain are also independently assorted only if they are part of different chromosomes. Genes in the same chromosome are passed on together as a unit. Such genes are said to be linked. For example, the "A" and "B" alleles (in the illustration below) will both be passed on together if the lower chromosome is inherited. "A" and "B" are linked due to their occurrence in the same chromosome. Similarly, "a" and "b" are linked in the other chromosome.

Genetic linkage continues
as homologous chromosomes
separate in the formation of
sex cells /

Linked genes most likely account for such phenomena as red hair being strongly associated with light complexioned skin among humans. If you inherit one of these traits, you will most likely inherit the other.

Genetic linkage of this sort can be naturally ended. During the first division of meiosis, sections near the ends of chromosomes commonly intertwine and exchange parts of their chromatids with the other chromosome of their homologous pair. This process of sections breaking and reconnecting onto a different chromosome is called crossing-over. In the example shown below, "A" and "B" are unlinked by this process.

Crossing-over unlinks alleles
of genes as homologous
chromosomes separate in
the formation of sex cells /

Crossing-over usually results in a partial recombination, or creation of combinations of alleles in chromosomes not present in either parent. For instance, the linkage between red hair and light complexion can be broken if the chromosome breakage occurs between the genes for these traits. The further apart the genes are from each other in a chromosome, the greater the likelihood that they will be unlinked as a result of crossing-over. Likewise, genes located closer to the ends, rather than the middle, of a chromosome are more likely to be recombined during meiosis. Subsequently, they are more likely to vary from generation to generation. As a consequence, it is probable that they provide more new genetic combinations that can affect the outcome of natural selection and the evolution of a population.

Crossing-over does not produce new alleles. Rather, it only exchanges existing alleles between homologous chromosomes.

Why Sex?

Sex Linkage

Sex linkage applies to genes that are located on the sex chromosomes. These genes are considered sex-linked because their expression and inheritance patterns differ between males and females. While sex linkage is not the same as genetic linkage, sex-linked genes can be genetically linked.

Sex Chromosomes

Sex chromosomes determine whether an individual is male or female. In humans and other mammals, the sex chromosomes are X and Y. Females have two X chromosomes, and males have an X and a Y.

Non-sex chromosomes are also called autosomes. Autosomes come in pairs of homologous chromosomes. Homologous chromosomes have the same genes arranged in the same order. So for all of the genes on the autosomes, both males and females have two copies.

A female’s two X chromosomes also have the same genes arranged in the same order. So females have two copies of every gene, including the genes on sex chromosomes.

The X and Y chromosomes, however, have different genes. So for the genes on the sex chromosomes, males have just one copy. The Y chromosome has few genes, but the X chromosome has more than 1,000. Well-known examples in people include genes that control color blindness and male pattern baldness. These are sex-linked traits.

Inheritence of Sex Chromosomes in Mammals

Meiosis is the process of making gametes, also known as eggs and sperm in most animals. During meiosis, the number of chromosomes is reduced by half, so that each gamete gets just one of each autosome and one sex chromosome.

Female mammals make eggs, which always have an X chromosome. And males make sperm, which can have an X or a Y.

Egg and sperm join to make a zygote, which develops into a new offspring. An egg plus an X-containing sperm will make a female offspring, and an egg plus a Y-containing sperm will make a male offspring.

  • Female offspring get an X chromsome from each parent
  • Males get an X from their mother and a Y from their father
  • X chromosomes never pass from father to son
  • Y chromosomes always pass from father to son

Sex Chromosomes in Pigeons

The way sex determination works in birds is nearly the reverse of how it works in mammals. If you’ve played Pigeonetics, you know that the sex chromosomes in birds are Z and W. Male birds have two Z chromosomes, and females have a Z and a W. Male birds make sperm, which always have a Z chromosome. Female gametes (eggs) can have a Z or a W.

  • Male offspring get a Z chromsome from each parent
  • Females get a Z from their father and a W from their mother
  • Z chromosomes never pass from mother to daughter
  • W chromosomes always pass from mother to daughter

In birds, it’s the males that have two copies of every gene, while the females have just one copy of the genes on the sex chromosomes. The W-chromosome is small with few genes. But the Z-chromosome has many sex-linked genes, including genes that control feather color and color intensity.

X & Y and Z & W are just two of the ways that sex is determined in animals. Some animals can even change from one sex to another. To learn more, visit Sex Determination.

Inheritance of Sex-Linked Genes

For genes on autosomes, we all have two copies—one from each parent. The two copies may be the same, or they may be different. Different versions of the same gene are called “alleles” (uh-LEELZ). Genes code for proteins, and proteins make traits.* Importantly, it’s the two alleles working together that affect what we see—also called a “phenotype.”

Variations in genes can affect our inherited characteristics, accounting for the differences from one individual to the next. For examples, visit Observable Human Characteristics and The Outcome of Mutation.

Female pigeons (ZW) have just one Z chromosome, and therefore just one allele for each of the genes located there. One gene on the Z chromosome affects feather color; three different alleles make feathers blue, ash-red, or brown. In a female bird (ZW), her single color allele determines her feather color. But in males (ZZ), two alleles work together to determine feather color according to their dominance. That is, 'ash-red' is dominant to 'blue', which is dominant to 'brown'.

Having two copies of a gene can be important when one copy is “broken” or defective. A functional second copy can often work well enough on its own, acting as a sort of back-up to prevent problems. With sex-linked genes, male mammals (and female birds) have no back-up copy. In people, a number of genetic disorders are sex-linked, including Duchenne muscular dystrophy and hemophilia. These and other sex-inked disorders are much more common in boys than in girls.

Red/green colorblindness is also caused by a defective gene on the X-chromosome. You need at least one working copy of the gene to be able to see red and green. Since boys have just one X-chromosome, which they receive from their mother, inheriting one defective copy of the gene will render them colorblind. Girls have two X-chromosomes; to be colorblind they must inherit two defective copies, one from each parent. Consequently, red-green colorblindness is much more frequent in boys (1 in 12) than in girls (1 in 250).

*Some genes code for functional RNAs, which also influence our traits.

The differences in sex chromosomes between males and females leads to specific inheritance patterns for sex-linked genes. (Above) Female pigeons inherit their color allele from their father. Males inherit one allele from each parent. In humans (below), the pattern is reversed.