Mendelian Genetics

1. Mendelian Genetics

2. Gregor Mendel (1822-84) • Known as the ‘father of genetics’ • Austrian monk who carried out work using pea plants to study the inheritance patterns of a number of traits • Formulated a number of ideas about the inheritance of characteristics – these are known as Mendel’s Laws of Inheritance

3. Mendel’s Laws of Inheritance • Theory of Particulate Inheritance • Mendel recognised that traits are determined by discrete units that are inherited intact down through generations – we now know these units are genes. • This model explained many observations that could not be explained by the idea of blended inheritance that was accepted at the time. • Law of Segregation • Two alleles separate unchanged during gamete formation i.e. (a Tt parent can produce both T sperm, and t sperm) • Law of Independent Assortment • Pairs of alleles on different chromosomes will segregate independently

4. Genotype and Phenotype • Genetic inheritance involves the genotype– the particular set of alleles possessed by an organism • The observable inherited characteristics of an organism are referred to as it’s phenotype • It is important to realize that the phenotype has both inherited and environmental components GENOTYPE + ENVIRONMENT = PHENOTYPE

5. The 3Hs • An organism that has two copies of the same allele is said to be homozygous for that allele and the organism is referred to as a homozygote. These organisms are also referred to as pure-breeding strains for the locus in question. • An organism that has two different alleles of a particular gene is said to be heterozygous for that allele and the organism is referred to as a heterozygote. • The above statements are true for autosomes, as individuals will carry two copies of the genes. The X chromosome is a different story. • Human males only carry one X chromosome so they can only have one copy of any allele found on the X chromosome. They are referred to as being hemizygous.

6. Dominant and Recessive Phenotypes • An important property of phenotypes is dominance - genes are not recessive or dominant. • Phenotypes may be completely dominant, incompletely dominant, codominant or recessive depending on their appearance in the heterozygote. • A dominant phenotype is one that is visible in the heterozygote and homozygote. • A recessive phenotype is one that is visible only in the homozygote. • Scientific convention dictates that the allele associated with a dominant phenotype is assigned an uppercase symbol (e.g. B) and the allele associated with the recessive phenotype is assigned the lowercase symbol (e.g. b) • Dominant does not mean the most common, and a dominant trait is not necessarily most frequently represented in pedigree.

7. Complete Dominance • In complete dominance homozygous and heterozygous individuals are generally indistinguishable. • The alternative phenotype, expressed only in the homozygote is said to be recessive. • Example: Eye colour • Brown eye phenotype is dominant over blue eyes • Assign B to allele associated with brown and brown and b to allele associated with blue • Homozygous individual BB has two copies of allele for brown eyed phenotype and will have brown eyes • Homozygous individual bb has two copies of allele for blue eyed phenotype and will have blue eyes • Heterozygous individual Bb has one copy of each allele and will have brown eyes

8. Incomplete dominance • With incomplete dominance, the phenotype is only partially expressed in the heterozygote, so the heterozygote has a different phenotype from either homozygote. • Example: Colour of snap dragon flowers • Snap dragons have a dark red phenotype or a white phenotype • Assigning R1R1 as genotype for red phenotype and R2R2 as genotype for white phenotype • Heterozygote has genotype of R1R2 and has pink phenotype. • In this case R1 codes for enzyme that promotes reaction that produces red pigment while R2 codes for defective enzyme. Flowers are white due to complete absence of enzyme in R2R2 homozygote, and pink in R1R2 heterozygote due to half the amount of enzyme being produced.

9. Codominance • With co-dominant phenotypes, the phenotypes of both homozygotes are expressed equally in the heterozygote. • Example: ABO blood system • There are three different alleles found at the locus for the ABO blood group, and individuals can have A, B, AB or O phenotypes. • People with AB blood groups are heterozygous. They have one allele that produces A antigen and one that produces B antigen. • A and B phenotypes are co-dominant. • Those with phenotype A or B may be homozygous or heterozygous, as the allele for the O phenotype does not code for expression of an antigen. This means that you can carry an allele corresponding to A phenotype and an allele corresponding to O phenotype but your phenotype will be A. • This means that O phenotype is recessive.

10. ABO Blood System

11. Other factors to consider • Multiple alleles at a single locus • Many genes have more than two alleles e.g. ABO blood systems and HLA antigens (markers of self) • Dominance relationships can only be established for a pair of alleles and these relationships can sometimes change due to environmental factors • Single genes with multiple effects • Some genes affect more than one phenotype. • These genes tend to be regulatory genes that control other genes that dictate development of a particular trait. • The lozenge gene in Drosophila controls differentiation of a number of tissues, and mutation can lead to a number of different phenotypic effects in the recessive homozygote in addition to the eye defect for which it was originally named. • The Tail-less mutation in mice is dominant, leading to mice with short or no tails. This mutation is also a recessive lethal, meaning that the homozygote for this mutation does not survive. This shows that the gene has at least one other function and that this function is essential for normal development of the organism.

12. Relationship between environment and phenotype • Identical twins are genetically identical as they arise from the separation of the daughter cells of a single fertilised egg. • Studies have shown that while their genotypes may be identical, their phenotypes can show differences. These differences must be attributable to different environments. • Better defined examples of the potential influence of environment of phenotype are provided by phenylketonuria (PKU), fur colour in Himalayan rabbits, and sickle cell anaemia. • Individuals with the disorder PKU are prone to mental retardation which can be prevented if diagnosed at birth and provided with a modified diet (environmental factor) • When a small region of white fur is shaved from the back of a Himalayan rabbit, the fur will grow back black if the animal is kept at low temperatures, but white if the animal is kept at high temperatures.

13. Effect of environment on phenotype of individuals carrying alleles for faulty b-haemoglobin productions

14. Monohybrid Cross • A monohybrid cross is a cross between two individuals involving a single genetic locus. • Procedure: • Select two strains that are pure-breeding for differing phenotypes (ie two homozygous organisms with different phenotypes). This is the parental generation. • Breed these to produce offspring. This is the first filial generation (F1). These individuals will all be heterozygous. • Breed F1 offspring to each other to produce second filial generation (F2). Examining the appearance offspring resulting from these crosses give us information about the about the pattern of inheritance of the trait being studied. • Punnet squares are used to illustrate the random combination of gametes and the resulting offspring in each generation

15. Examples of monohybrid crosses • Complete dominance • Parental Phenotypes: • red eyes or white eyes • F1 Phenotypes: • all red eyes • F2 Phenotypes: • 3 red eyes, 1 white eyes • Incomplete dominance • Parental Phenotypes: • red or white flowers • F1 Phenotypes: • all pink flowers • F2 Phenotypes: • 1 red, 2 pink, 1 white

16. Rules for Monohybrid Crosses • A 3:1 phenotypic ratio will be observed in F2 generation if the following conditions apply: • The variation in the trait is controlled by a single gene. • The gene is on an autosome. • There are two alleles of the gene. • One phenotype is dominant. • A 1:2:1 phenotypic ratio will be observed in F2 generation if the following conditions apply: • The variation in the trait is controlled by a single gene. • The gene is on an autosome. • There are two alleles of the gene. • One phenotype is incompletely dominant or the phenotypes are co-dominant

17. Dihybrid Cross • A dihybrid cross is a cross between two individuals involving a two genetic loci. • Procedure: • Select two strains that are pure-breeding for both genetic loci. This is the parental generation. • Breed these to produce offspring. This is the first filial generation (F1). These individuals will all be heterozygous and have the same genotype. • Breed F1 offspring to each other to produce second filial generation (F2). Examining the appearance offspring resulting from these crosses give us information about the about the pattern of inheritance of the trait being studied. • Punnet squares are used to illustrate the random combination of gametes and the resulting offspring in each generation

18. Example of a dihybrid cross • Coat color is indicated by B (brown, dominant) or b (white). • Tail length is indicated by S (short, dominant) or s (long). • Parents are homozygous for each trait (SSbb and ssBB). • F1 generation are heterzygous at both loci and only show the dominant phenotypes. • F2 generation all combinations of coat color and tail length occur: • 9 are brown/short (purple boxes), • 3 are white/short (pink boxes) • 3 are brown/long (blue boxes) • 1 is white/long (green box).

19. Rules for Dihybrid Crosses • A 9:3:3:1 phenotypic ratio will be observed in the F2 generation if the following conditions apply: • The two genes control two distinct traits • There are two alleles for each of the genes • For each trait one phenotype is dominant • Both genes are on autosomes • The two genes assort independently

20. Back crosses and test crosses • A back cross is a cross between the F1 heterozygote and either one of the pure-breeding (homozygous) parental strains. • A test cross is a cross between F1 heterozygote and the parental strain showing the recessive phenotype. • Test crosses are carried out to determine whether an individual of dominant phenotype is homozygous or heterozygous. • Test crosses also provide an answer as to whether the phenotypic variation we observe is due to the segregation of alleles (meaning phenotype is controlled by one gene) or independent assortment (indicating phenotype is controlled by two genes).

21. Examples of test crosses Test cross involving single gene Offspring phenotypic ratio 1:1 Test cross involving two gene Offspring phenotypic ratio 1:1:1:1

22. Interpreting phenotypic ratio results in F2 and testcross offspring • F2 ratio 3:1 Testcross ratio 1:1 • One phenotype is dominant, the other recessive. • Trait is inherited by segregation of alleles of single autosomal gene • F2 ratio 1:2:1 Testcross ratio 1:1 • The heterozygote is of distinct phenotype because of incomplete dominance or codominance. • Trait is inherited by segregation of alleles of single autosomal gene • F2 ratio 9:3:3:1 Testcross ratio 1:1:1:1 • For each of the two traits there is a dominant and a recessive phenotype. • Each trait is determined by a single autosomal gene. • The alleles of each gene assort independently.

23. Linked Genes • Linkage is the tendency for two or more genes located on the same chromosome to be inherited together. • The closer they are, the more likely they are to be inherited together. • Linkage is never complete because of crossing over during meiosis. • Linkage and the phenomenon of crossing over can be used to determine the distance between genes on a chromosome. • Linked genes can be denoted in the following ways when the allele arrangements are known. These include : A b Ab/aB A b a B a B

24. Inheritance of linked genes • Assume two genes P and V are linked: • Parental cross • PV/PV x pv/pv • F1 • All PV/pv • Will have dominant phenotype • F2 • See punnet square to right • When crossing two F1 heterozygotes for two linked gens, and disregarding crossing over, the ratio of the phenotypes is close to 3:1

25. Detecting Linkage • The results of test crosses between known double heterozygote with a double homozygous recessive allow us to determine if two gene loci are linked. • If the two gene loci are not linked, the genes will assort independently and the outcome of the test cross will be four classes of offspring in equal proportions • If the two gene loci are linked, there will be four classes of offspring but the proportions of these will not be equal. Instead, there will be an excess of offspring from parental gametes and a deficiency of offspring from recombinant gametes. • Genes are ‘linked’ when the percentage of recombinant gametes falls below 50%.

26. Estimating the distance between linked genes • From the results of a test cross with linked genes, it is possible to estimate the distance between the gene loci. • This estimate is based on the percentage of recombinant offspring. Distance between loci = 100 × number of recombinant offspring total number of offspring • The percentage of recombinant offspring corresponds to the number of map units separating the two genes.

27. Estimating the distance between linked genes • There are 12 per cent total recombinant offspring, therefore the loci of the two genes are separated by about 12 map units. • The chromosome make-up of the cross can be represented as:

29. Gene interactions • Aspects of phenotype are often influenced by more than one gene. • Two or more genes may interact to produce a particular phenotype. • One such example is the inheritance of a type of deafness in humans. • This hereditary deafness is due to the action of two unlinked genes, each with two alleles. • The allele pairs can be represented as D and d, and E and e. • At least one D and one E is required for normal hearing. • If either or both loci are homozygous, dd or ee, deafness results. • The following genotypes will produce deaf individuals: DD ee, Dd ee, dd EE, dd Ee, dd ee

30. Gene interactions in human deafness • Consider a family in which both parents are heterozygous for these genes and have normal hearing: • DdEe x DdEe • The genotypes look the same as in a standard dihybrid cross, but the resulting phenotypes do not give the typical 9:3:3:1 ratio • There is a probability of 9/16 (unshaded) normal hearing and 7/16 (shaded) deafness.

31. Handy Hint • If you are working out probabilities when the phenotype results form the interaction of two or more genes, you cannot rely on typical ratios you might expect in the cross. • You need to work the example out in a punnet square and identify the phenotypes from the resulting genotypes.