Discovery of Linkage

William Bateson and R.C. Punnett were working with several traits in sweet peas, notably a gene for purple (P) vs. red (p) flowers, and a gene for long pollen grains (L) vs. round pollen grains (l).

LINKAGE
Linkage is defined genetically as the failure of two genes to assort independently. Linkage occurs when two genes are close to each other on the same chromosome. Genes far apart on the same chromosome assort independently: they are not linked. Linkage is based on the frequency of crossing over between the two genes. Crossing over occurs in prophase of meiosis 1, where homologous chromosomes break at identical locations and rejoin with each other.

Recombination and Crossing over is an exchange of genetic material between homologous chromosomes. prophase of meiosis 1 Synapsis Recombinase genetic consequence of crossing over is each chromosome that goes into a gamete is a combination of maternal and paternal chromosomes Occurs between non sister chromatids. that

Recombination

Mechanism of crossing-over

Example for linked gene Genes for red hair and freckles are linked together.

Parental gametes are those gametes that maintain the original linkage of genes (alleles) [RX] in the chromosome. Recombinant gametes are those in which the original linkage is undone due to exchange of chromosomal pieces by crossing over during meiosis. [Rx, rX] Genes far apart on the same chromosome assort independently: they are not linked. Recombination frequency, or crossing over rate, is the percentage of recombinant gametes made by crossing over (in relation to the number of parental gametes made). It always refers to two genes located in the same chromosome. The farther the distance between the loci of two genes in a chromosome the higher the recombination frequency between these genes. Centimorgan, or recombination unit, by convention is a distance between two linked genes that corresponds to 1% of recombination frequency of these genes. For example, if a gene A has a recombination frequency of 20% with the gene B, thenthat the gene A is 20 centimorgans distant from the gene B.

Genetic mapping
- is the determination of the location of the genes in a chromosome. By determining the recombination frequency between several different linked genes it is possible to estimate the distance between them in the chromosome. For example, if a gene A has a recombination frequency of 20% with the gene B, this gene B has recombination frequency of 5% with the gene C and this gene C has recombination frequency of 15% with the gene A, it is possible to assert that the gene A is 20 centimorgans distant from the gene B and that between them lies the gene C at 15 centimorgans of distance from the gene A. Gene mapping, also called genome mapping, is the creation of a genetic map assigning DNA fragments to chromosomes. genetic markers Two different ways of mapping are distinguished. Genetic mapping uses classical genetic techniques (e.g. pedigree analysis or breeding experiments) to determine sequence features within a genome. Using modern molecular biology techniques for the same purpose is usually referred to as physical mapping. In physical mapping, the DNA is cut by a restriction enzyme. Once cut, the DNA fragments are separated by electrophoresis. The resulting pattern of DNA migration (i.e., its genetic fingerprint) is used to identify what stretch of DNA is in the clone. Association mapping: linkage

Sturtevants Interpretation Sturtevant, Morgans undergraduate student, discovered frequency of crossing over between each pair of the 3 genes: yellow, white 0.5%

white, miniature yellow, miniature 35.4%

34.5%

Sturtevant reasoned that recombination frequencies were additive, so order of genes on chromosome was yellow-white-miniature.

Morgan traced a gene to a specific chromosome - Morgan used Drosophila fruit flies for his experiments - only 4 pairs of chromosomes

- wild type flies have red eyes - white eyes is a mutant phenotype - Morgan mated the white-eyed male to a red-eyed female - all F1 offspring were red-eyed - The F2 offspring were not 3:1; instead all females were red-eyed while half of the males had red and half had white eyes - eye color was linked to the flys sex Genes located on sex chromosomes are called sex-linked genes - Morgans evidence that a specific gene is carried on the X chromosome helped confirm the chromosomal theory of inheritance.

linked genes: genes that are located on the same chromosomes and tend to be inherited together - linked genes deviate from expected Mendelian ratios -ex. in flies body color and wing shape are inherited together

Genetic recombination: the production of new combinations of traits inherited from two parents yellow-round x green-wrinkled YyRr x yyrr

Parental types: when the offspring phenotypes are identical to the parents - ex YyRr, yyrr Recombinants: when the offspring phenotypes are new combinations ex Yyrr, yyRr When 50% of all offspring are recombinants, we say there is a 50% frequency of recombination - 50% frequency is observed for genes located on different chromosomes Geneticists can use recombination data to map a chromosomes genetic loci Genetic map: an ordered list of the genetic loci along a particular chromosome Linkage map: a genetic map based on recombination frequencies Map of body-color (b), wing-size (vg) and cinnabar (cn) - cn and b is 9%

- cn and vg is 9.5% - b and vg is 17% Sex-linked genes have unique patterns of inheritance - fathers pass sex-linked alleles to daughters, but not sons - mothers pass sex-linked alleles to both sons and daughters Because males only have one locus, they cannot be heterozygous Sex-linked disorders in humans - muscular dystrophy: 1/3500 males in the US - hemophilia: absence of proteins for blood clotting

Nondisjunction: the members of a pair of homologous chromosomes do not move apart properly during meiosis I or II. - gametes are (n+1) or (n-1) if they have too many or too few chromosomes Aneuploidy: having an abnormal chromosome number Trisomic: a chromosome in triplicate (2n+1); ex. trisomy 21 (Downs syndrome) Monosomic: if a chromosome is missing (2n-1)

Polyploidy: organisms that have more than two complete chromosome sets - triploidy (3n) - tetraploidy (4n) Polyploids are more normal in appearance than aneuploids

Sex-linked inheritance Genes that control various traits which are found on the X and Y chromosome are called sex-linked gene. The Y chromosome is shorter than the X chromosome. It does not have many alleles that are found on the comparable portion of X chromosome. Hence, in the male, any trait caused by a dominant or recessive allele that is found on the X chromosome, will be expressed.

Haemophilia

Haemophilia is a condition which the blood does not clot normally. This condition is due to the lack of a protein needed for normal blood clotting. If often results in excessive bleeding. The ability to produce a protein for the blood to clot is due to a dominant allele. An individuals inability to produce the protein is caused by a recessive allele found on the X chromosome. Individual who suffer from hemophilia are called hemophiliacs. Hemophiliacs can bleed to death from minor wounds. We can show the inheritance of haemophilia by using letters. To represent the normal dominant allele on the X chromosome, we use XH. The genotype for normal female is XH XH . The genotype of a heterozygous normal female is XH Xh . Heterozygous females are known as carrier of disease. A normal male XH Y and haemophiliac male is Xh Y. A sex-linked gene shows a criss-cross method of inheritance. This means the inheritance is from father to daughter and mother to son. This is due to the fact that the Y chromosome carries no such homologous allele on the same locus.

Schematic diagram of the sex-linked inheritance of haemophilia

From the example, it can be seen that the haemophilia gene is passed from the mother to son. The probability of getting a normal son or a haemophiliac son is 0.5. The daughter are all normal but it is 50% likely that one of the daughters is carrier. The probability of the son to be a haemophiliac is higher compared to the daughter. This is because the recessive haemophilia gene is able to express itself in a male individual.

Colour blindness Colour blindness is a condition in which colours cannot be distinguished. In most cases, a person who suffer from this condition is unable to distinguish between red and green colours. Colour blindness is caused by a recessive allele carried on the X chromosome. The pattern of inheritance of this condition is similar to haemophilia. We can represent a normal vision gene as XC and a colour blind gene as Xc.

Thalassaemia Thalassaemia is a childhood disease.

This disease is caused by a recessive gene and affects the haemoglobin in the red blood cells. The red blood cells of a person with Thalassaemia are smaller. They may be deformed and pale in colour. This is because the haemoglobin content is less. Thalassaemia is common among people in Mediterranean and South-East Asian countries.

Huntingtons disease Huntington disease is caused by a single gene mutation which causes nerves to degenerate. This causes brain cells to die leading to behavioral changes and loss of mental powers.