Modification of Mendelian Ratios PDF

Modification of Mendelian Ratios Chapter 4 1 Two Modes of Inheritance So far we have looked at each mode of inheritance on its own and how they alter the 3:1 monohybrid ratio Combinations of two gene pairs with two modes of inheritance should therefore modify the 9:3:3:1 dihybrid ratio Let`s look at...

Modification of Mendelian Ratios Chapter 4 1 Two Modes of Inheritance So far we have looked at each mode of inheritance on its own and how they alter the 3:1 monohybrid ratio Combinations of two gene pairs with two modes of inheritance should therefore modify the 9:3:3:1 dihybrid ratio Let`s look at an example... 23 Example Cross between two individuals who are both heterozygous for the autosomal recessive gene that causes albinism and who are both blood type AB. What is the probability of a particular phenotypic combination occurring in each of their children? 24 25 Gene Interaction Several genes can influence a particular phenotypic characteristic – Much more complex than Mendel had envisioned Epigenesis – each step of development increases the complexity of the end product Each gene must carry out its activities in a timely fashion, at the correct place, and at the appropriate level – Think of an orchestra! Gene interaction occurs in: – Metabolic pathways – Signal transduction – Developmental pathways (next slide) 26 Gene Interaction Inner ear development is a good example of gene interaction and epigenesis at work During ear formation, a cascade of intricate developmental events occur, influenced by many genes Mutations that interrupt many of the steps lead to a common phenotype – Hereditary deafness The mutant phenotype is called a heterogeneous trait because of the many genes involved – Over 50 genes are involved in the development of our hearing, but only a few alleles are common in causing deafness http://www.everydayergonomics.org/aginge rgonomics/Photos/innerear.png 27 28 Epistasis Some of the best examples of gene interaction are those of epistasis Epistasis: occurs when an allele of one gene masks the expression of alleles at another gene – An interaction between non-allelic genes – The gene that does the masking is called an epistatic gene – The gene that is being masked is called a hypostatic gene Examples: 1. 2. 3. The homozygous presence of a recessive allele prevents or overrides the expression of other alleles at a second locus (Recessive epistasis) A single dominant allele at a locus masks the expression of an allele at another locus (Dominant epistasis) Two recessive alleles at either of two different loci are capable of suppressing a phenotype (Duplicate recessive epistasis) 29 The Bombay Phenotype A and B antigens for blood type are derived from a precursor molecule called the H substance In rare cases, the H substance is incompletely formed and cannot be properly modified This results in the expression of blood type O and is called the Bombay phenotype Due to a rare recessive mutation at a locus separate from that controlling the A and B antigens (FUT1) Even if IA and/or IB alleles are present, the blood type will be type O A case in 1952 for a woman that had type O blood but one of her parents had type AB blood!!! 30 The Bombay Phenotype This is an example of a homozygous recessive condition at one locus masking the expression of a second locus IA IB Hh x IA IB Hh Use the forked-line method to calculate the final phenotypic ratio 31 32 Key Points We were only observing one characteristic and not two (unlike the pigmentation and blood type example ) Even with only one character being followed, we got phenotypic ratios in sixteenths – So we know for sure that there is another gene involved! J In this previous example we witnessed a modification of the dihybrid 9:3:3:1 ratio In the following examples, epistasis combines one or more of the four phenotypic categories in various way – There are six possible ratios when dealing with dihybrid crosses à 33 Gene Interaction Pierce. Genetics: A Conceptual Approach 7th 34 Gene Interaction Summary – The classic F2 ratio is often modified in cases when gene interaction controls phenotypic variation – It is possible to identify such cases when the final ratio is expressed in sixteenths – The number of phenotypes may decrease from the typical four we have witnessed so far 35 Gene Interaction Can produce novel phenotypes – i.e. non-parental phenotypes 36 Complementation Problem: What if two mutations cause a similar phenotype? There are many complex processes that involve several genes to produce one phenotype – E.g. hearing, wing development, eye colour Complementation analysis allows us to determine if the mutations are in the same gene or separate ones 37 Complementation Example Consider two true-breeding strains of wingless Drosophila – Two different mutations, both recessive The assumption might be that both strains have mutations in the same gene – But wing development is a complex process involving many genes Are the two mutations that yield similar phenotypes (wingless) present in the same gene or in two different genes? To answer this, we cross the two mutant strains and analyze the F1 generation – There are two possible outcomes.. 38 39 Complementation All mutations determined to be present in any single gene are said to fall into the same complementation group – There can be more than two mutations in a complementation group 40 Pleiotropy We have looked at multiple genes influencing a single trait, but the opposite can also occur – i.e. the expression of a single gene may have multiple effects One gene can influence multiple, seemingly unrelated phenotypic traits http://www.nature.com/scitable/content/6514/pleiotropy_diagram_mid_1.jpg 41 Pleiotropy: Marfan Syndrome Autosomal dominant disorder resulting from a mutation in the gene encoding for the connective tissue fibrillin Fibrillin is widespread in many tissues of the body and one would expect multiple effects from such a defect In fact, the phenotype associated with Marfan syndrome includes lens dislocation, increased risk of aortic aneurysm, and lengthened long bones in limbs 42 Pleiotropy: Porphyria variegata Autosomal dominant disorder resulting in the inability to metabolize porphyrin and heme Excess porphyrin is evident in the urine and causes toxicity in the body, especially the brain People with more severe forms are highly sensitive to sunlight and may suffer from acute delirium – Some sufferers have reddish mouths and teeth, due to irregular production of the heme pigment 43 Sex Chromosomes Sex is determined in many species by a pair of unlike chromosomes – Usually designated X and Y Males = XY Females = XX The two chromosomes behave as a “homologous” pair – Synapse and segregate during meiosis However, much of the Y chromosome is considered to be inert genetically – i.e it lacks most genes present on the X chromosome 44 X-Linkage Genes present on the X chromosome exhibit unique patterns of inheritance compared with autosomal genes – This pattern is called X-linkage Occurs when genes are present on the X but absent from the Y chromosome – How does this modify the Mendelian ratios? 45 X-Linkage in Drosophila First observed in the white mutation in the eyes of Drosophila in 1920 – Wild-type is red eyes and is dominant Thomas H. Morgan – Observed that the inheritance pattern of the white-eye trait was related to the sex of the parent with the mutant allele Unlike Mendelian monohybrid reciprocal crosses, these reciprocal crosses did not yield identical data (i.e. F1 and F2 phenotypes were not the same irrespective of which P1 had the recessive mutant trait) – Concluded that the white locus is present on the X chromosome Red ♀ x white ♂ White ♀ x red ♂ 46 47 X-Linkage in Drosophila The differences in the F1 and F2 phenotypic ratios depend on whether the P1 white-eyed parent is male or female The recessive allele for white eyes is found on the X chromosome – Females have two available gene sites (XX) and males have only one (XY) 48 49 X-Linkage in Humans The Y chromosome lacks most of the genes on the X chromosome Whatever alleles are present on the X chromosome of a male will be expressed directly in their phenotype Males cannot be homozygous or heterozygous for X-linked genes – They are hemizygous 50 X-Linkage in Humans 51 X-Linkage in Humans Crisscross pattern of inheritance – Traits controlled by recessive X-linked genes are passed from homozygous mothers to all sons A pedigree helps to easily identify these Xlinked traits If the X-linked trait is lethal or debilitating prior to reproductive age, then only males will be affected – Females can only be carriers 52 Colour Blindness (red-green) 53 Genetic Maternal Effect Genes are inherited from both parents; however, the offspring phenotype is determined by the genotype of the mother & https://www.cell.com/fulltext/S0092-8674%2805%2901223-7 54 Sex-Limited and Sex-Influenced Inheritance Occurs when the sex of the organism affects the phenotype controlled by an autosomal gene Sex-limited inheritance – Expression of a specific phenotype is limited to one sex Sex-influenced inheritance – The sex on an individual influences the expression of a phenotype that is not limited to one sex or the other Examples – Sex-limited: Neck and tail plumage in domestic fowl Hen-feathered vs cock-feathered – Sex-influenced: Pattern baldness in humans, body hair, muscle mass, etc. 55 Genotype Phenotype in Females Phenotype in Males hh hen-feathered cock-feathered Hh hen-feathered hen-feathered HH hen-feathered hen-feathered 56 Genotype Phenotype in Females Phenotype in Males BB bald bald Bb nonbald bald bb nonbald nonbald 57 Environment and Gene Expression We think of varying phenotypes are the result of genotype – Assumption: a particular genotype always produces the same phenotype But sometimes the same genotype can result in different phenotypes 1. Gene-environment interaction 2. Interactions of with alleles of other genes in the genome The degree of expression of a particular trait can be quantified by determining penetrance and expressivity of the genotype in question 58 Penetrance When the phenotype of an organism is consistent with its genotypes, we define this organism to be penetrant for the trait Incomplete penetrance can be expressed by a percentage – If a mutation in the gene responsible for a particular autosomal dominant disorder has 95% penetrance, then 95% of those with the mutation will develop the disease, while 5% will not An allele is said to have complete penetrance if all individuals who have the disease-causing mutation have clinical symptoms of the disease Anything that shows less than 100 % penetrance is described as incomplete penetrance 59 Expressivity Sometime the discrepancy between genotype and phenotype is a matter of degree (not absence presence) – The range of expression of the mutant genotype Can be measured quantitatively (enzyme concentration) or qualitatively (eye colour) 60 Environment and Gene Expression Phenotype can be altered due to environmental factors – Diet, temperature, oxygen levels, humidity, light cycles, and the presence of mutagens Expression can vary during the lifetime of an organism 61 Environment and Gene Expression A reduction in the phenotypic variation in a controlled environment indicate that the environment does influence expression If a lab environment is held constant and extensive phenotypic variation (penetrance and expressivity) is still observed, other genes may be modifying the phenotype In truth, both are modifying the phenotype 62