Genetics Chapter 5: Extensions and Mods of Basic Principles I. Intro A. Cuenots experiments--coat color in mice 1.

Crosses of two yellow mice made a mix of yellow and gray in a 3:1 ratio 2. Yellow supposedly dominant over gray, but Yy x Yy made 3/4 Y_ and 1/4 yy 3. Taking these Y_ offspring, some shouldve been YY, and crossing them would get all yellow progeny...but this never happened 4. REASON: yellow x yellow gives a 2:1 ratio of yellow and nonyellow...the allele for yellow was lethal when homozygous, which was why all mice were heterozygous Yy...Yy x Yy made mice that died in development, leaving two Yy to yy. 5. Yellow allele: acts RECESSIVE in development (only lethal when YY) but DOMINANT in color B. Cuenots other experiments 1. More than two alleles can exist at one locus 2. genes on more than one alleles interact for coat color 3. Some mice have hereditary disposition to cancer 4. Genes encode enzymes 5. All of this proves that Mendels basic principles are not wrong, just modified for todays use II. Additional factors at a single locus can affect the results of genetic crosses A. Not all factors have complete dominance 1. incomplete dominance: when a heterozygote has a phenotype intermediate between the phenotypes of the two homozygotes 2. Flower ranges: red to white, A1A1 makes red flower, A2A2 makes white a) If heterozygote A1A2 produces same amount of pigment as the A1A1 homozygote (aka RED flower) than it is complete dominance b) If flower makes no pigment and is A1A2, flower will be white, A2 dominant to A1 c) If flower color inbetween, then it is A1A2 and incomplete dominance 3. Another example: PP purple x pp white=Pp Pp violet offspring, so inbetwen a) Their progeny is 1:2:1 ratio genotypically and phenotypically...1 will be PP purple, two Pp violet and one pp white

4. Remember: incomplete dominance ONLY affects how phenotype appears B. Codominance 1. Phenotype of heterozygote is not an intermediate but displays BOTH phenotypes of the homozygotes at the same time (like MN blood types) 2. People with L^M L^M have M blood type, L^M L^N have MN...not very good for immunological reactions C. Dependency of type of dominance on level of phenotype observed 1. Phenotypes can be observed at anatomical, physiological and molecular level...type of dominance of a character depends on level youre looking at 2. Cystic fibrosis: people have two copies of mutated CFTR allele and make defective CFTR protein that doesnt let a channel let chloride ions out of the cells...people heterozygous (one good CFTR, one bad one) make good and bad proteins, displaying codominance on the molecular level but recessive on the physiological level because you still make enough good protein D. Characteristics of dominance 1. Dominance is allelic interaction...interactions between genes at the same locus 2. Does not alter how genes are inherited, only the way expressed as phenotype 3. Classification of dominance depends at the level youre looking at E. Penetrance and expressivity 1. When a genotype does not always produce the expected phenotype, this is incomplete penetrance (human polydactyly...can have dominant allele for it but have a normal number of fingers) 2. Penetrance: percentage of individual organisms having a particular gentype that expresses the predicted phenotype (38 people have polydactyly/42 who have the allele=90% penetrance) 3. Expressivity: degree to which a character is expresses (i.e. some people w/ polydactyly only have a little flap of extra skins, while others have dozens and thousands of extra fingers) 4. All these terms are due to presence of other genes/environmental factors (a gene may encode an enzyme that makes a phenotype only at a certain temp.) F. Lethal alleles 1. Causes death at an early stage of development so that some genotypes may not appear among the progeny

2. Lethal alleles usually recessive, but can be dominant...wont be transmitted until dont happen till the onset of reproduction (Huntingtons disease) G. Multiple alleles 1. For some loci, more than two alleles are present within a group of organisms...this is multiple alleles/allelic series 2. The genotype of each individual diploid organism still has only two alleles...inheritance the same, just more possibilities of genotypes/phenotypes 3. Example: duck feather patterns a) M^R dominant>M>m^d b) anything w/ M^R makes a restricted pattern; MM and Mm^d makes mallard, and only m^d m^d makes dusky color c) NUMBER OF POSSIBLE GENOTYPES: [n(n+1)]/2 n=# alleles 4. Example: ABO blood group a) I^A makes antigen A, B antibody (to eat foriegn B blood platelets) b) I^B makes B antigen, A antibody c) I^A I^B are equal so display codominance, no antibody d) and then ii makes no antigen (O blood type), two antibodies (A and B)...this is why blood transfusions need compatible blood types!!!! e) Blood typing can exclude paternity, but not prove that a person is the parent of a child because a lot of people have the same blood type (Charlie Chaplin got lucky) III. Gene interaction takes place when genes at multiple loci determine a single phenotype A. Intro to this concept 1. Mendels dihybrid 9:3:3:1 ratio shows that the genes at each locus are independent in their assorment and in their phenotypic expression 2. This doesnt always happen: the genes at one locus depend on the presence of genes at OTHER loci...this is gene interaction 3. The products of genes at (two different loci in our case) combine to produce new, unpredictable phenotypes B. Gene interaction that produces novel phenotypes 1. Gene interaction where genes at two loci make a single characteristic: fruit color in peppers a) YYCC x yycc=YcYc, F2= 9/16 Y_C_ red, 3/16 Y_cc peach, 3/16 yyC_ and 1/16 yycc

b) Y locus and C locus interact to produce a single phenotype--the color of the pepper (Y locus makes one enzyme, C locus another to make color) c) With gene interaction, you have to determine the probabilities of each locus separately, then use multiplication on genotypes, not phenotypes, to get overall probability C. Gene interaction with epistasis 1. In gene interaction, this is where one gene masks the effect of a gene at another locus 2. Epistasis like dominance, but dominance goes with genes at the SAME locus...this with genes at DIFFERENT loci 3. Gene that does the masking: epistatic gene...can be recessive or dominant 4. Gene whose effect is masked is a hypostatic gene 5. Recessive epistasis a) Example: lab color (MAGGIE!) b) One locus determines pigment produced by skin cells...B makes black pigment, b makes brown c) Another determines hair pigment color: E lets the black or brown pigment made by B to be deposited in hair, where e prevents dark pigment deposition...therefore, ee MASKS the expression o the black and brown alleles at the first locus d) Example 2: Bombay phenotype (see book pg 108), suppresses the expression of alleles at the ABO locus 6. Dominant epistasis a) only a single copy of an allele is required to inhibit the expression of the allele at a different locus b) In squash, W allele inhibits Y alleles from showing any color, making the squash white (pg 109) 7. Duplicate recessive epistasis a) Two recessive alleles at either of two loci are capable of suppressing a phenotype b) Example: albinism in snails, which is the absence of pigment; results from the presence of either of two recessive alleles at two different loci c) 9:7 ratio of pigmented to albino when AaBb crosses, because have to have aa, bb or aa bb to be albino

d) This ratio is because pigment is probably a two step process...A needs to be converted into compound B by enzyme 1, and B to C by enzyme 2...if any part recessive, the whole train will stop...therefore, albinism arises because of an absence in compound C D. Complementation: determining whether mutations are at the same locus or at different loci 1. Example: in fruit flies, white is an X linked recessive mutation that makes white eyes; apricot is also an X-linked recessive mutation...are they on the same locus? 2. Carry out a complementation test: parents homozygous for different mutations are crossed, making heterozygous babies a) If the mutations occur at the same locus (allelic), then the heterozygous offspring only have mutant alleles (lets say just a and b) b) If at different loci, the parents will have wild type genes at the other locus (aa b+b+ and a+a+bb) so the offspring will have the wildtype phenotype...this is complementation E. Dog coat color pages 113-115...do we have to know? IV. Sex influences the inheritance and expression of genes in a variety of ways A. Now were looking at the influences of sex and how they effect the expression of genes on: 1. autosomal chromosomes 2. in the cytoplasm 3. characteristics in which the genotype of only the maternal parent determines the phenotype of the offspring 4. Expression of genes on autosomal chromosomes is affected by sex of parent w/ whom genes are inherited B. Sex influenced and sex limited characteristics 1. Sex influenced: characteristics determined by autosomal genes and inherited normally, but expressed differently in males versus females...more readily expressed usually in one sex over the other (so higher penetrance) a) i.e. beards in goats... B+B^b, B^b B^b in males bearded, but only B^b in females bearded b) females need two B^b alleles, males only need one for the beard to show up 2. Sex limited is encoded by autosomal genes, but expressed in only ONE sex, zero penetrance in the other

a) for male chickens, HH and Hh gives hen feathering, but hh gives cock feathering...all three genotypes in female chickens give them the hen feathering b) In humans: male-limited precocious puberty results from autosomal dominant P that is only expressed in males...not at all expressed in females C. Cytoplasmic inheritance 1. Mendels assumptions of genetics are based on if the genes are located on chromosomes in the nucleus of the cell...but this is not always true. Some characteristics are encoded by genes located in the cytoplasm 2. A few organelles (mitochondria and chloroplasts) have DNA 3. A zygote inherits cytoplasmic genes from only ONE of the gametes, usually just the egg, so the traits are present in both males and females and passed from MOTHER to offspring, changing reciprocal crosses 4. Have a LOT of phenotypic variation because not assured to be evenly distributed in cell division like chromosomes a) Most cells contain thousands of mitochondria, each w/ two to ten copies of DNA...if half of them contain a normal copy of mtDNA and half a mutant one, just by chance, one new cell could get all the bad copies and one get all the new copies...so different progeny w/ the same mother and same cells may vary in phenotypes b) Same w/ chloroplast DNA (cpDNA) 5. Studied by Carl Correns in four-o-clock plant a) Discovered that the branches of a same strain produced different colored leaves...some all green leaves, some all white...color of the flowers depended ONLY on the seed (white flower seeds made white flower), so only from mother, not father (which would be pollen) b) Some egg cells got chloroplasts with normal cpDNA to make green flowers...others with only abnormal cpDNA made white progeny...other eggs cells with a mix of normal and abnormal made varigated progeny in leaves 6. Mitochondrial diseases a) In humans, disorders arise from mutations in mtDNA which occur in genes encoding components of electron-transport chain that generate ATP b) Leber hereditary optic neuropathy...cells die in optic nerve. Traits passed only from mother to all children. D. Genetic maternal effect...sometimes confused w/ cytoplasmic inheritance

1. the phenotype of the offspring is determined by the genotype of the mother, but genes are inherited from both patents 2. Substances in cytoplasm of an egg are pivotal in early development, so thats why get moms phenotype 3. Example: coiling of a snail shell a) Dad dextral coiling (s+ s+), mom sinistral (ss), F1 (s+s) and sinistral because that was the mothers phenotype b) This has to do with the way that the cytoplasm divided after fertilization, which is determined by a substance produced by the mom c) F2 (s+ s) self fertilized...since s+ s would normally encode a dextral shell, thats what happens d) Progenys phenotype is determined by the mothers GENOTYPE, not phenotype!!! E. Genomic imprinting 1. Mendelian genetics says that reciprocal crosses give identical results...this not always the case 2. The differential expression of genetic material depending on whether its from the male of female parent is genomic imprinting 3. Example: Igf2, insulin growth factor II a) offspring get one allele from mom, one from dad, but paternal copy is expressed while maternal copy is silent b) This is the opposite in other genes...for some, the paternal copy is silent 4. Disorders w/ this a) Prader-Willi: children inherit missing portion of chromosome 15 from dad b) Angleman syndrome: children inherit missing portion of chromosome 15 from mom...different syndromes than what happens w/ Prader-Willi c) Mostly has to do w/ growth d) Methylation (adding CH3 to DNA) has to do with imprinting...we think...it is usually erased in the germ cells for each generation, then reestablished as gametes are made in different levels of methylation, causing differential expression 5. Imprinting and genetic conflict: hypothesis is that there are different and conflicting evolutionary pressures acting on maternal and paternal alleles for gene that affect fetal growth a) w/ evolution, paternal alleles that max. the size of the offspring are favored, so it is an advantage to pass on male alleles

b) However, maternal alleles are spread out so the female to reproduce in the future c) Hypothesis: genomic imprinting will evolve so paternal copies of genes that affect fetal growth will be maximally expressed where maternal copies will be silent 6. Epigenetics: heritable traits caused by alterations to DNA a) Methylation is one...amount of it shows whether a gene will be expressed in offspring or not...reversible change to DNA, pattern can change when DNA goes through a gamete b) Example: queen bees and worker bees both female, but queen bees are fertile, worker bees not c) Worker bees feed special larvae royal jelly to make them turn into queens...others fed normally and turned into workers...this diet affects the expression of the genes, because both worker bees and queen bees are genetically the same d) Royal jelly silences the expression of Dnmt3, which adds methyl groups to DNA; DNA less menthylated, the genes that are silenced in workers are expressed in the queen V. Anticipation is the stronger/earlier expression of traits in succeeding generations A. Anticipation: a genetic trait becomes more strongly expressed at an earlier age as it is passed from generation to generation...can also get worse too VI. The expression of a genotype may be affected by environmental effects A. The genotype sets the potential for development, but how the phenotype actually develops depends on the environmental effects 1. i.e. fly vg vg makes small wings at lower temperature, longer wings at higher temperature 2. So far, environment hasnt had a big deal in what weve discussed B. Environmental effects on the phenotype 1. Temperature-sensitive allele: allele whose product is functional only at certain temperatures (about rabbits on pg 123) 2. Expression of human genetic disease: PKU an autosomal recessive allele that causes defect in an enzyme that metabolizes an amino acid phenylalanine, causing a buildup of the amino acid...putting a kid on a low-phenylaline diet stops retardation 3. Clearly, genes and their products interact w/ environmental factors

4. Environmental factors alone can sometimes produce a phenotype that is the same as the phenotype produced by a certain phenotype: this is a phenocopy C. The inheritance of continuous characteristics 1. Discontinuous characteristics have a few easily distinguished phenotypes (coats of dogs black, brown or yellow; peas wrinkled or round) 2. Continuous characteristics are characteristics that vary consistantly, like human height (also can be quantitative characteristics) a) frequently influenced by environment 3. Arise because different genes at multiple loci produce a phenotype 4. Number of genotypes encoding a characteristic is 3^n, where n is the number of loci, each with two alleles, that influence the characteristic a) Characteristics encoded by genes at many loci are polygenic characteristics b) The opposite of this is pleiotropy, in which one gene affects multiple characteristics (1) Example: y lethal gene on mice, which has effect on hair color, diabetes obesity and tumors in mice 5. Polygenic continuous characteristics influenced by environmental factors are multifactorial characteristics, because many different genes AND the environment influence the phenotype; phenotypes also dont sort into specific types 6. No ratios for this--we have to use statistical analysis (coming up in a later chapter!!!!) TIME TOOK TO READ pg 99-125: 2 hours, 27 minutes