biol139-lecture7-2011

biol139-lecture7-2011 - Topic Topic Modifications of...

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Unformatted text preview: Topic Topic Modifications of Mendelian Ratios Chapter 3 Chapter pp 43 - 53 pp pp 79 - 103 iGenetics pp Mendel’s traits were: (3:1) • single genes with alternate alleles • clear cut dominance + recessiveness What about extensions to Mendel’s work? Single gene interactions: • deviations from dominance/recessive • Can a gene (trait) have more than two alleles? • Can a trait be influenced by more than one gene? Multifactoral: • phenotype result of interaction of 1 or more genes • gene-gene • gene-environment • both Single Gene Interactions: Single Dominance is not always complete ! Codominant dominance : Full phenotypic expression of both Codominant purebred parental traits in F1 hybrid –neither trait is dominant or recessive to each other) dominant Snapdragon Flower Colour Show Incomplete Dominance Single gene traits for flower colour Flower colour allele = CR for Red (C is for colour and R for Red) (C Flower colour allele = Cw for White (C is for colour and W is for white) white) For incomplete and co-dominance it is correct to express the alleles as both uppercase with capitals How can you explain the Incomplete dominance? Trait = flower colour Gene =produces a protein for flower colour pigmentation pathway Alleles = red or white CR allele = functional protein = pigment production = red flowers (wild type?) Cw allele = non functional protein, no pigment = white flowers Pure-breeding lines Half the enzyme reduces pigment and dilutes colour Double dose of enzyme gives red Non functional enzyme gives white This is because only half the red pigment is produced in the F1 (with CR and CW alleles -heterozygote), resulting in offspring that are pink and do not resemble either of their parents. (still use uppercase capitals to show incomplete dominance) What if we selfed the pink F1 progeny? What would the F2 progeny look like? Genotype ratio is 1:2:1 (reflects Mendel’s ratios of alternate 1:2:1 alleles for single gene trait) BUT, phenotype ratio is reflection of genotype ratio ! Trait Seed Coat Pattern = C Spotted S Dotted D Codominance Codominance Neither is dominant or recessive to each other Selfed Example ABO system ABO blood grouping is an example of a multiple allele system and codominance O No sugar A and B are antigens on RBC surface and H group (lipid) Non-antigenic Specific sugar groups attached to lipids on membrane surface of RBC Gives RBC’s their antigenic properties. The ABO blood group involves a single gene I which is responsible for the sugar groups (trait). single • This single gene I has multiple alleles (IA, IB and i ) O No sugar Phenotype (blood group) Possible or or only O In terms of sugars on cell surface (phenotype): In IA + IB are codominant to each other and dominant to i are codominant to dominant ii individuals are recessive to both A and B ii recessive Codominance ABO system Codominance Anti-B Anti-A No Ab codominant both show up in heterozygote individual in F1 Heterozygotes IAIB produce both types of sugars on their cell surface. Persons Antibodies would be found within the plasma component i.e. if you were type A you would have anti-B antibodies in serum Packed RBC: If you were a donor/recipient, this would be transfused not the serum These are the antibodies that would be present in the recipients own serum These are the antigens or sugars that would be present on the individuals RBC Blood group I I is a universal recipient should have no antibodies for A and B in serum so can accept A, B or O blood antibodies Blood group I is considered a universal donor for blood transfusions Since transfusing packed RBC’s matters what is on surface of the donors blood and what blood type the recipient is in terms of antibodies in their serum Summary: Summary: Variations on complete dominance are consistent Variations with Mendel’s law of segregation with The type of dominance relationship exhibited by different alleles does not affect the way they are does transmitted. Rather, it is a reflection of the way in which the proteins they encode act in the cell. • • • genes still occur as paired units in cell paired law of segregation still applies segregation reflect differences in how gene products control gene phenotype! A gene may have more than two alleles gene Multiple alleles exist for most genes e.g. blood type : A (IA), B (IB), O (i) e.g. lentil seed coat pattern: spotted, dotted, clear (no e.g. pattern), marble, or marble-2 pattern), e.g. drosophila eye colours white, red, or eosin e.g. mouse coat colour black, black and tan, or agouti Remember: The allele that predominates in populations of the organism in the “wild” is the “wild-type allele”. The other alternative allele(s) are the mutant alleles. mutant Such genes are said to have multiple alleles, BUT a diploid organism can only have two copies of these alleles. A gene may have more than two alleles Some of the Alleles Present at the White Locus of Drosophila Locus responsible for eye colour in Drosophila. More than 100 mutant alleles have been identified at the white locus In Drosophila, w+ is wild and phenotypically brick-red colour Range from w (white) to near wild-type (white-satsuma) when alleles are homozygous. In each case, total amount of pigment in these mutant eyes was reduced compared to Wild-type New Alleles Arise Through Mutation New Gene I produces surface cell sugars that are located on RBC’s Altered forms of the wild-type allele that arose by mutation during evolution I A IB I i Frequency of mutations in gametes can be very low (1/1,000,000) Chance alteration in genetic material arise spontaneously in nature Each mutation makes a slightly different form of the enzyme Can only inherit 2 copies of any one allele copies Lentils Offer Another Example of Multiple Alleles • e.g. lentil seed coat pattern: 5 different alleles e.g. • spotted, dotted, clear (no pattern), marble-1, Marble-2 spotted, How to Determine Dominance Relationships Between How Multiple Alleles (Allelic Series) Multiple •crosses can be made between pure-breeding lines representing all phenotypes to establish the dominance relationships between all possible pairs of alleles all This reveals a dominance series, in which alleles are listed in This dominance order from dominant to recessive. A dominance series 5 alleles for lentil coat colour Dominant to recessive Don’t forget, dominance is meaningful only in context of 2 alleles Don’t A gene may have more than two alleles gene New alleles arise through mutation ↑ Survivorship (↑ successful reproduction) ↑ frequency of allele Survivorship frequency in population (species) population (species) ↓ Survivorship (↓ successful reproduction) ↓ frequency of allele Survivorship frequency in population (species) population (species) Allele frequency The proportion of all copies of a gene in a population that are of a given allele type (usually expressed as a %) • must be able to follow transmission of “new mutant alleles” through expression in phenotype through Allele Frequency It is usually expressed as a percentage and describes the amount of genetic diversity at the individual, population or species level. Example: assuming that in a human population there are 100 individuals. Each of them would have two alleles for a particular trait, the total number of genes in this population is 200 (=100 x 2). If out of the 100 individuals, there are 30 homozygous dominant (AA), 50 heterozygous (Aa), and the remaining 20 are homozygous recessive (aa). Therefore, the total number of dominant genes in the population is (30 x 2) + (50 x1) = 110. [That is, (30 x 2) from the 30 homozygous (AA) plus (50 x1) from the 50 heterozygous (Aa)] Thus, the frequency of the dominant trait (A) is (110/200) = 0.55 or 55%. Similarly, the total number of recessive genes in the population is (20 x 2) + (50 x 1) = 90. [That is, (20 x 2) from the 20 homozygous (aa) plus the (50 x 1) from the heterozygous (Aa)] The frequency of the recessive trait (a) is (90/200) = 0.45 or 45%. Mutant allele : usually < 1 % Mutant results from altered genetic information altered • loss or decreased function or no change loss decreased no Monomorphic : gene with only one wild-type allele (agouti gene occurs with frequency greater than 99% in nature) gene Polymorphic : gene with more than one wild-type allele Frequency % (U.S.whites) (ABO blood types) Blood type (ABO A B AB O 41% 11% 4% 44% A gene may have more than two alleles Mice: Trait coat colour Mice: • Agouti gene: (wild-type A) Agouti • overall appearance = dark grey overall Tip of hair black and yellow • camouflage camouflage • wild rabbits, mice, squirrels wild Genotype A_ 14 mutant alleles found for agouti gene (coat colour) 14 t t a a = black back/yellow belly black and is recessive to A aa = all black A_ = wild type A_ and is recessive to A • black backed killed by predation in wild • in nature A has a frequency of > 99% • A is called a monomorphic allele monomorphic How can we determine A is dominant Another dominance series Another F1 Interbreeding of F1 gives F2 all with a 3:1 ratio One gene may contribute to several One visible characteristics Pleiotropy – Multiple phenotypic effects caused by Multiple a single gene - distinct, seemingly unrelated distinct, 1. New Zealand Tribesmen: 1. • recessive allele, single gene trait recessive • Wild type gene makes protein regulates cilia, flagella Wild Homozygous recessive males Homozygous • respiratory problems (cilia) respiratory • sterile (flagella) sterile 2. Marfan Syndrome: • autosomal dominant single gene trait dominant • gene encoding the connective tissue protein fibrillin • multiple effects in body (CT very extensive) • lens of eye, lining of blood vessels (aorta), bones, tendons ligaments, cartilage, heart valves etc. Phenotype associated with Marfan syndrome • lens dislocation • aortic aneurism • lengthened long bones of limbs Some alleles may cause lethality- A Variation on Pleiotropy Pleiotropy Some alleles may result not only in a visible phenotype, but also Some affect viability. An allele that results in death of an organism is called a lethal allele, and the gene involved is called an essential gene and Essential genes when mutated can result in lethal phenotype Essential if mutation is caused by a recessive lethal allele, only homozygotes for that allele will have the lethal phenotype will if mutation is caused by a dominant lethal allele, both dominant homozygotes and heterozygotes for that allele will have the will lethal phenotype (i.e. Huntington's) lethal The assignment of dominant and recessive pertains only to the phenotype being The regarded regarded Recessive lethal alleles Recessive A variation on pleiotropy : some alleles may result not only variation in a visible phenotype (light yellow fur), but also affect in yellow ), viability (lethal –for development) viability Variation of agouti = very light yellow coat colour (AY) • don’t know dominance? • don’t know genotype of yellow (Ay_ ) Yellow mice of unknown genotype and dominance? A Ay Purebred Ajouti If complete dominance and y F1 Conclusions Conclusions yellow mice carry (A) allele, yellow y homozygous (A A ), expect all yellow or agouti in F1 depending on which allele is dominant yellow X yellow cross produced skewed ratio in F 2: yellow • 1/3 Agouti and 2/3 Yellow 1/3 • F 2 ratio of 2:1 not 3:1 (phenotype) or 1:2:1 (genotype) 2:1 • Agouti mice breed-true, but yellow do not (ie. no AyAy) Allele for yellow coat is dominant to ajouti for coat colour, but recessive for viability (recessive lethal allele) 2:1 phenotypic/genotypic ratio in F2 between two heterozygous P is characteristic of recessive lethal allele the 1/4 of the progeny that are homozygous AyAy die 1/4 • one copy of allele produces yellow coat one • 2 copies are lethal –recessive lethal allele copies Hemoglobin Molecule Sickle cell syndrome : Sickle Beta gene mutated to give sickled protein S = wild type allele s = sickled allele α α β β 1. Multiple alleles: 1. β-globin gene has both wild-type allele (S) and 400 mutant alleles Most common is sickle cell (s) 2. Pleiotropy Multiple phenotypic effects caused by single gene with mutated s allele Lysis of RBC But Resistance to Malaria -sickle cells do not support growth of Plasmodium Low RBC counts 3. Recessive Lethality: ss individuals 3. ss usually die young of complication usually Homozygous ss Clog BV Multifactorial Inheritance Most common traits are determined by more than one gene Most Multifactorial – arising from the action of two or more genes Multifactorial (polygenic), or from interaction between genes and the interaction environment environment Remember Mendel’s Single Gene traits: • Followed 2 unrelated phenotypic traits: unrelated • pea colour and seed shape etc. pea • Each trait was a single gene with alternate alleles (Yy Ss) Each • Showed complete dominance / recessiveness dominance • Assorted independently of each other independently Remember Mendel found if the phenotypes determined by the allelic pairs for two independently assorting genes are distinct two distinct (yellow/green; round/wrinkled) and there is complete dominance, then we will get the familiar dihybrid phenotypic ratio of 9:3:3:1 in the F2. But what if the phenotypes determined by the allelic pairs of two independently assorting genes are not distinct? That is they control the independently same general phenotypic attribute (trait). colour Two alleles for seed coat shape Two alleles for seed coat seed seed Distinct Phenotypic expression in progeny for both traits both OR Will we get novel phenotypes? modified ratios Two alleles for seed coat colour seed Two alleles for seed coat colour seed Gene A Gene B SAME phenotypic trait Seed colour Novel (unique) phenotypes can arise from the combined interaction of alleles from two different (independent) genes (A and B) for a single, individual trait e.g. seed coat colour in lentils Two Genes Can Interact to Determine One Trait Interaction of two allelic pairs in a dihybrid cross which affect the same phenotypic same characteristic can result in their gene products giving novel phenotypes novel e.g. seed coat colour in lentils (single trait/2 genes involved) seed Phenotypes: brown, tan, gray and green tan gray green Let A = Gene 1 and B = Gene 2 Tan A dominant to B recessive purebreeding Gray A recessive to B dominant Brown: both alleles A+B when dominant and in combination result in new phenotype Individual traits can be determined by more than one gene gene 4 genotypic classes Green results from lack of either dominant alleles double recessive (aabb) Phenotypic ratio 9:3:3:1 indicative of 2 genes responsible for Phenotypic genes coat colour acting independently in simple complete coat independently dominant and recessive manner dominant Two alleles for seed coat colour seed Two alleles for seed coat colour seed Gene B Gene A SAME phenotypic trait Seed colour For Lentils A_ B_ TAN pigment (A_bb) Two genes in two different pathways GRAY pigment (aaB_) A_B_ dihybrid Gene A + Gene B • results in BROWN pigment BROWN • both tan and gray pigments are produced • which precipitates out into Brown Brown When neither allele A or B is present then default colour is Green in lentils Green Notice: same ratio as for Mendels dihybrid cross, except in this case only one trait (seed coat colour) is affected Branching Pathway: F1 genotype = AaBb (all) F1 phenotype = All brown brown F2 phenotypic ratio F2 phenotypic ratio for Bb x Bb for Aa x Aa 3/4 B_ 3/4 A_ Combined F2 ratios ratios 9/16 A_B_ = Brown Brown 1 /4 b b 3 /4 B _ 3/16 aaB_ = Gray Gray 1/4 bb 1/4 aa 3/16 A_bb = Tan Tan 1/16 aabb = Green Green 2 genes in two different pathways interact independently to produce genes two independently seed coat colour in lentils. Each genotypic class A-B-, A-bb, aaB- and aabb produce a particular phenotype (colour –interaction of products at biochemical or produce interaction biochemical cellular level) cellular Comb Shape in Chickens: Comb Gene interaction and modified dihybrid ratios Gene • • • several genes can influence a particular trait several may not necessarily interact directly may cellular functions of a # of genes contribute to development of common phenotype development • i.e. eye: complexity, size, shape, texture, colour i.e. • interaction of 2 or more genes can produce variations interaction on simple F2 dihybrid ratios (9:3:3:1) on Examples of genes interacting in same biochemcial in pathway: Complementary gene action Complementary Two or more genes can work in tandem in the same tandem biochemical pathway to produce a particular trait biochemical • complementary or cooperative complementary Sweet peas: (9:7 ratio) Sweet • wild sweet pea plant has purple flower (wild-type) wild • purple is dominant to white (F2 ratio of 3:1) • also true breeding white flowered plants (selfed) also • occasionally when crossed pure breeding sweet peas with white crossed flowers they give rise to all purple flowered F1 progeny purple • selfed purple F1 progeny give 9:7 purple:white 9:7 Complementary gene action Complementary Two or more genes can work in tandem in the same biochemical tandem pathway to produce a particular trait pathway • complementary or cooperative complementary Crossed pure breeding white flowered sweet peas give rise to all purple F1 progeny… How does this happen Let A = Gene 1 Let B = Gene 2 • 2 enzymes work in tandem to catalyze 2 separate biochemical steps in tandem the pathway for flower colour the • At least one dominant copy (heterozygous) of each allelic pair (A and B) copy must be present to give colour must • That is the genes complement each other complement Allow F1 progeny to self Double heterozygotes for A and B Double 3 genotypes combine to give 1 phenotype • selfed purple F1 progeny give 9:7 purple:white 9:7 Complementary Gene Action with 2 genes gives a characteristic ratio of 9:7 in F2 characteristic Epistasis Epistasis A gene interaction in which the effects of alleles of one gene interferes or masks the phenotypic of masks phenotypic expression of the alleles of another gene The phenotype is governed by the epistatic gene epistatic Epistatic = control over another gene Lab Coat Colours Lab Produced by 2 independently assorting genes for coat colour Produced Black = B_ dominant e = epistatic gene Brown = bb ee = recessive epistasis E_ = does not influence colour, but E_ allows for colour to be deposited in fur (i.e. expression of Gene B) (i.e. ee = no expression of Gene B, default of ee no colour is yellow (epistatic) no Recessive epistasis Recessive e.g coat colour in Labrador retrievers Gene 1 Gene B_ = black bb = brown Gene 2 E_ = no colour effect ee = yellow • ee double recessive overides ee all other coat colour regardless of dominance ! Variation of 9:3:3:1 ratio in Variation F2 due to masking of alleles by recessive epistasis (ee) Phenotypic ratio 9:3:4 Phenotypic indicates recessive Epistasis Epistasis bbee ee is always yellow, is no matter what B/b is is pale eyes and nose Can 2 parents who are phenotypically O have child that is A blood type? that Recessive epistasis e.g. h Bombay allele in blood type H/h controls production of lipid H to which sugars A and B are attached Gene 1 H/h Gene 2 I/i hh is recessive epistatic to I gene hh is always type O regardless of what I/i is Recessive epistasis of H allele Recessive Mother blood type 0 X Genotypes: ii H_ ii H_ Father blood type 0 IA_ hh hh Child blood type A Genotype: IAi Hh Hh Epistatic gene Dominant epistasis Dominant e.g. Summer squash colour Gene 1 A_ = yellow yellow aa = green green Gene 2 Gene B_ = white (epistatic to A or a) white bb = no colour contribution B_ is dominant to A_ dominant Dominant epistasis Dominant epistasis means the allele causing the epistasis is dominant dominant Modifications to dihybrid 9:3:3:1ratios Modifications Complementary gene action Two or more genes can work in tandem, in the same biochemical Two tandem in pathway to produce a particular trait pathway Heterogeneous trait Heterogeneous • Many different genes generate a developmental or biochemical pathway (50 genes for hearing) biochemical • It takes a dominant wild-type allele at each of these dominant genes to produce a normal development or product genes A homozygous recessive mutation at any one of a homozygous number of genes can give rise to the same phenotype number (i.e. deafness) Sweet pea flower colour (9:7 ratio) is an example of a heterogeneous trait heterogeneous that can be complemented with at least one dominant allele at each step in pathway Deafness an example of genetic heterogeneity and complementation •2 different recessive genes different • results in heterozygotic results progeny with hearing progeny • same recessive gene same • results in homozygotic results progeny with deafness progeny Mutation in 2 different genes results in same phenotype The wild-type phenotype can be rescued by complementation Ebony = e Both genes autosomal Need at least one dominant allele of each gene in pathway to make wild type (brown) body colour (they complement each other) N.B. wild-type allele is designated with superscript + To determine if 1 gene or 2+ genes are involved in producing a particular phenotype, we must use complementation testing Complementation testing can also be used to determine if 2 individuals have mutations in the same gene Question: are 2 mutations which yield similar phenotypes present on same gene or 2 different genes? present same different U.S. and Canada isolated and established true breeding wingless U.S. flies (recessive phenotypes - isolated independently) recessive isolated Mutation in separate genes Mutation Mcan MUSA Wingless Mutation in same gene Mcan MUSA Mutant Wingless Complementation The same genotype does not always result in the same phenotype in • Examples so far have been for expression of certain phenotypes reliably reflected in the genotype Some mutants always expressed as distinct Some phenotypes i.e. wrinkled peas phenotypes Some similar to wild-type allele Some • but range in phenotypes (gradated) but Variables can modify gene expression: Variables • influence of environment environment • modifier genes genes • chance chance Degree of expression of particular trait being studied is Degree quantified by looking at penetrance penetrance penetrance – percentage of the population with a particular penetrance genotype, that demonstrate the expected trait (phenotype) genotype, Depends on genotype and environment Complete penetrance Huntingtons 100% of population with certain genotype show expected phenotype (express trait) ! phenotype Incomplete penetrance less than100% of population with certain population genotype show genotype expected phenotype expected For example, if 80% of individuals in population who carry a particular gene show expected phenotype then it has 80% penetrance Expressivity – the degree or intensity with which a Expressivity penetrant gene or genotype is expressed in a phenotype within a population population a gene could have 100% penetrance in regards to genotype, but show gene variable expressivity in regards to phenotype (severe, moderate, mild) Examples of Incomplete Examples penetrance and variable expressivity retinoblastoma retinoblastoma • malignant form eye cancer malignant • dominant mutation one gene dominant • not all persons carrying the allele not get the disease get •75% of people who carry mutant allele develop disease -25% don’t allele • may express in one eye, both eyes may Neurofibromatosis • tumor like growth over body tumor • 50-80% penetrance 50-80% • but those that get it show different expressivity expressivity Mild to severe symptoms • lots of tumors on body • high blood pressure, • tumors of eye, brain spine etc. The same genotype does not always result in the The same phenotype Modifier genes Modifier May have up to 50 genes in a pathway, but some are major and others just modify phenotype modify Alter the phenotypes produced by the alleles of other Alter phenotypes genes genes Mouse tail length is dictated by a wild type tail length gene A modifier gene (T gene) with various alleles will shorten tail length from wild length Achieved various mutations of the T-gene (alleles) which shortened length of tail in mice from 75% to 10% as long as wild each mouse line carries different alleles of the modifier T gene (expressivity) Environment Environment Factors such as temperature, light, Factors temperature and altitude can affect the phenotypic expression of a genotype Temperature-sensitive enzymes Function at one temperature, but not at another Environment Environment The environment can affect the phenotypic expression of a The genotype genotype Siamese cats homozygous for a temperature sensitive enzyme • variant form of allele (coat colour) called “siamese” does not function at normal body temperature. Temperature sensitive mutant is non functional at higher temps Functional at lower temps. 25oC artificially cooled Use of temperature-sensitive mutations Use to study genes involved in DNA replication Wild-type clb28 mutant 23° 23° Conditional mutant: a particular allele allele which is lethal only under certain which conditions conditions Permissive temp: temperature at which the allele (enzyme) is functional Phenotype is indistinguishable from wildtype 35° 35° Restrictive temp: temperature at which the allele (enzyme) is non-functional non-functional Phenotype is distinguishable from wild-type Red = total genomic DNA Yellow = newly replicated DNA Chance Chance Occurrences in the lives of individuals can influence the expression of some can alleles. alleles. e.g. exposure to carcinogens, radiation Q: How can one determine if trait is caused by alleles Q: of 1 gene or alleles of 2 or more genes? A: Breeding Studies: • look for phenotypic ratios that would suggest 2 or more look genes interacting i.e. 9:7, 9:3:4, 12:3:1 etc genes • check hypothesis with further breeding studies check i.e mice coat colour Deciding between different hypotheses using specific breeding tests • in F1 get novel phenotype in • could be 2 genes or 1? could • 1 like lentils when cross gray X tan got all brown in F • could this be similar where 2 dominant alleles for could each gene are present to give novel F1 colour? i.e. B _ C _ i.e. F2 ratio of 9:3:4 suggests recessive epistasis 9:3:4 suggests recessive Test cross • F2 = 9 black, 3 brown and 4 white BB,Bb,bb BBcc So one scenerio for genes B and C: cc is epistatic to all other alleles to give white C_ = no effect; bb = brown B_ = Black Variety of progeny from test cross Bbcc bbcc Deciding between different hypotheses using specific breeding tests Deciding • could be the possibility of one gene could with 2 alleles • bb = albino bb • BB = brown BB • Bb = black - incomplete dominance incomplete • Is it possible that this ratio is 1:2:1? 1:2:1 •This would suggest 1 gene This gene • - incomplete dominance incomplete • Again, use a cross to verify this Again, hypothesis hypothesis • All black progeny All Test-crossing is not an option in humans, so pedigrees can be used to determine the genetic basis of particular diseases be • like deafness, albinism example of heterogeneity like Albinism can result from mutations in more than one gene - genetic heterogeneity than genetic • horizontal inheritance suggests both parents have recessive allele in one gene gene ...
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This note was uploaded on 10/04/2011 for the course BIOL 139 taught by Professor Christinedupont during the Spring '10 term at Waterloo.

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