Outline of major topics
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Outline of major topics • Allelic actions and interactions • Dominance • how it works • when there is no real dominance • Multiple alleles • Lethal alleles Outline of major topics ... • Genic interactions • Metabolic pathways • novel phenotypes • epistasis • (pleiotropy) Outline of major topics ... • Factors affecting phenotype • Genetic factors • Strange genes • Environmental factors Allelic actions: dominance • In general, dominant allele codes for production of functional protein • P --> purple pigment • In general, recessive allele codes for no functional protein • p --> no pigment Allelic actions: dominance ... PP has two alleles coding for purple pigment Pp has one allele coding for purple pigment, one allele coding for nothing pp has no alleles coding for pigment Allelic actions: dominance ... • In many cases, a simple dominant/recessive relationship does not hold • incomplete or co-dominance Incomplete or Co-dominance • If both alleles code for a contrasting functional protein, heterozygote shows a phenotype completely different from either homozygote! • Two different upper case letters used to symbolize the alleles or one letter w/ superscripts Incomplete or Co-dominance ... • Flower color in carnations • R codes for a red pigment • W codes for a white pigment • RR gives a red flower • WW gives a white flower • RW gives a pink flower Incomplete or Co-dominance ... Phenotypic ratios = genotypic ratios Pink X Pink --> 1/4 Red, 1/2 Pink, 1/4 White R W R RR RW W RW WW Incomplete or Co-dominance ... Andalusian fowl: black X black --> black white X white --> white black X white --> gray (blue) gray X gray --> ? Incomplete or Co-dominance ... • heterozygote shows a BLEND: alleles are incompletely dominant • heterozygote shows BOTH: alleles are co- dominant Incomplete or Co-dominance ... MN Blood grouping (Landsteiner and Levine) two alleles: M - produces M antigens N - produces N antigens Incomplete or Co-dominance ... Genotypes: Phenotypes: M MM Type M; has only M antigens M M (Anti-N antibodies) M M N MN Type MN; has both antigens (no antibodies) N M N NN Type N; has only N antigens N N N (Anti-M antibodies) Incomplete or Co-dominance ... • Incomplete dominance = co-dominance • Just label differently depending on whether phenotype shows BLENDING • Mechanism generally the same; both alleles code for a working protein Multiple alleles • May be > just two choices of alleles at one locus • Population level phenomenon; individuals have, at most, two different alleles (heterozygous) Multiple alleles ... ABO Blood Groupings Four possible blood types (phenotypes): A B AB O Controlled by one gene ABO Blood Groupings ... Three alleles, with co-dominance as well as as dominant/recessive relationship Alleles: A, B, O (or IA IB IO) Phenotype (blood type) is a result of the proteins coded for by each allele ABO Blood Groupings ... A codes for A antigen B codes for B antigen O codes for no antigen ABO Blood Groupings ... AA Type A: A antigens; anti-B antibodies AO BB Type B: B antigens; anti-A antibodies BO AB Type AB: A & B antigens; no antibodies OO Type O: no antigens; anti-A and anti-B antibodies ABO Blood Groupings ... • O is recessive to both A and B • A and B are co-dominant • Blood type AB is considered the “universal recipient” • no antibodies produced • Blood type O is considered the “universal donor” • no antigens produced Reminders ... • Dominance is not an inherent property of an allele • An allele may be dominant to a second allele, but co-dominant, incompletely dominant, or even recessive to a third Coat color in rabbits Four alleles: c+ cch ch ca agouti chinchilla Himalayan albino c+ is dominant to all others cch is incompletely dominant to ch and ca ch is dominant to ca Coat color in rabbits ... c+ __ agouti cch cch chinchilla cch ca light gray cch ch light gray w/dark tips ch ch or chca Himalayan c a ca albino Multiple alleles ... • Many, if not most, genes do have multiple possible alleles • Rhesus blood group (+ or -) • actually at least 18 alleles • One white eye locus in Drosophila • over 100 alleles Lethal alleles • First described by Cuenot in 1905 • coat color in mice • strain with yellow coats • yellow dominant to wild-type agouti • could not produce true-breeding (homozygous) yellows Lethal alleles ... • Each time Cuenot crossed two yellow mice, 1/3 of the offspring were agouti • Backcrossed yellow mice to agouti, saw all yellow mice were heterozygotes • Impossible to produce homozygous yellow mice! Lethal alleles ... • Castle and Little offered explanation: • yellow allele dominant w/ respect to coat color • yellow allele also a recessive lethal allele • homozygous yellows die as embryos Lethal alleles ... Yellow X Yellow cy c+ cy c+ c+ cy cycy do not live to birth Apparent ratio: c+ c+c+ cyc+ 2/3 yellow : 1/3 agouti cy cyc+ cycy Lethal alleles ... • Mechanisms of lethality • recessive lethals: not coding for some necessary product • Hemophilia: dominant allele --> clotting factor recessive allele -> no clotting factor • Sickle cell anemia: S --> normal hemoglobin s --> abnormal hemoglobin Lethal alleles ... • Mechanisms of lethality … • Dominant lethals: very rare. Gene product itself causes death • Huntington’s disease: H --> type of neurotoxin h --> no neurotoxin • Retinoblastoma: R --> allows tumor formation r --> no tumor formation Lethal alleles ... • Once again, note that “dominance” in itself means nothing. • Refers only to phenotype that appears in the heterozygote • Lethals may be dominant with respect to one phenotype and recessive with respect to the lethal action Genic interactions • Two or more genes acting on one trait • Novel phenotypes • Epistasis • One gene acting on more than one trait • Pleiotropy ***All due to metabolic pathways*** Genic interactions: Novel Phenotypes Eye color in Drosophila P: red eyed x white eyed F1: red eyed F2: 9 red eyed 3 brown eyed 3 scarlet eyed 1 white eyed Genic interactions: Novel Phenotypes S = wild-type (red) B = wild-type (red) s = scarlet b = brown S __ B __ --> wild-type (red) S __ bb --> brown eyes ss B __ --> scarlet eyes ss bb --> white eyes Genic interactions: Novel Phenotypes The S allele controls the production of BROWN pigment The B allele controls the production of SCARLET pigment Cpd. Y ---enzyme S---> BROWN RED Cpd. X ---enzyme B---> SCARLET Genic interactions: Novel Phenotypes Poultry: comb shape Two genes, w/ 2 alleles each: pea vs. single, and rose vs. single Considered separately: AA, Aa = pea BB, Bb = rose aa = single bb = single Genic interactions: Novel Phenotypes Poultry comb shapes ... The genotype at each of 2 loci plays a role in determining comb shape: A__ B__ = walnut aa B__ = rose A__ bb = pea aa bb = single Genic interactions: Epistasis • One gene masks a second gene • Due to a linear, instead of branched, metabolic pathway Genic interactions: Epistasis Coat color in mice B = agouti A = non-albino b = black a = albino A__ B__ = agouti A__ bb = black aa __ __ = albino Genic interactions: Epistasis Coat color in mice ... Colorless black enzyme A pigment precursor enzyme B agouti pattern Genic interactions: Epistasis Coat color in mice ... Aa Bb X Aa Bb: 9 AB agouti 3 Ab black 4 (3 aB + 1 ab) white Epistasis: Coat color in Labs B = black E = black or chocolate b = chocolate e = yellow E__ B__ Black E__ bb Chocolate ee B __ Yellow ee bb Yellow Genic interactions: Epistasis Fruit color in summer squash aa bb = green aa B__ = yellow A__ __ __ = white Aa Bb x Aa Bb How can we distinguish allelic interactions from genic interactions? • While the F2 ratios will not follow basic Mendelian rules, they still provide information • Allelic interaction (one gene) will lead to a deviant 3:1 • 1:2:1 most likely • Genic interaction (2 genes) will lead to a deviant 9:3:3:1 • 9:3:4 12:3:1 9:6:1 9:7 • 3 genes: deviant 27:9:9:9:3:3:3:1 Pleiotropy • One gene may affect more than one trait • This is again due to the metabolic pathways involved Pleiotropy • PKU - phenylketonuria • P codes for phenylalanine hydroxylase • enzyme metabolizes phenylalanine • p does not code for functional enzyme • phenylalanine cannot be metabolized • primary result: mental retardation • also affects head size, skin/hair/eye color, “mousy” odor, peculiarities of gait, stance, sitting posture, eczema, epilepsy Pleiotropy: PKU metabolic pathway protein phenylalanine phenylpyruvic acid (PKU) phenylalanine hydroxylase tyrosine transaminase melanin Other factors affecting phenotype • Overview • Genetic factors • Incomplete penetrance • Variable expressivity • Sex limited and sex influenced traits • Environmental factors • Nutrition, light, temperature, etc..... Incomplete Penetrance and Variable Expressivity • Incomplete penetrance • Identical genotypes differ in phenotype • Penetrance = % individuals w/ genotype expressing the associated phenotype • Variable expressivity • Variation in the degree of expression of the phenotype Incomplete Penetrance Eye shape in Drosophila Lobe locus: dominant allele which reduces the size of the eye LL Ll ll reduced eye normal eye Incomplete Penetrance However, only 75% of the flies carrying the L allele actually have reduced eyes. 25% of the LL and Ll individuals have eyes which appear perfectly normal; just like ll flies. The penetrance of the lobe allele is said to be 75%. Variable Expressivity • Neurofibromatosis - autosomal dominant • 1/3 virtually symptom free; presence of café-au-lait spots & benign skin tumors • 1/3 symptom free most of the time; episodes of acute illness • 1/3 severely affected; symptoms severe enough to cause death Sex Limited Traits • Traits which appear exclusively in one sex • All genotypes possible in both sexes • One phenotype limited to one sex • Generally regulated by a hormone level threshold • Any secondary sexual characteristic is sex limited Sex Limited Traits Horns in some breeds of sheep: H+ = production of horns H- = no horns H+H+ H+H- H-H- males: horns horns no horns females: no horns no horns no horns There must be a sufficiently high level of testosterone for horns to be produced. Only males have enough! Sex Influenced Traits • Sex determines which allele is dominant • male and female heterozygotes differ in phenotype! AA AB BB males: A A B females: A B B Sex Influenced Traits Horns in Suffolk sheep: h+ h+ h+ h- h- h- males: horns horns no horns females: horns no horns no horns Again, related to hormonal thresholds. Sex Influenced Traits Male pattern baldness: Testosterone threshold. B = bald N = not bald BB BN NN males: bald bald not bald females: thinning not bald not bald Environmental effects on phenotype • The environment may greatly influence the expression of genotypes • light • temperature • nutrition • cosmetics • drugs Environmental effects on phenotype • Light • Corn: sunred allele - homozygous plants bright red when grown in full sun • Appear green if all but red light screened • Humans: freckles (dominant) - phenotype is a combination of presence of allele and exposure to sunlight Environmental effects on phenotype • Temperature • Primroses: red flowers if reared at room temperature; white flowers if >86o F • Rabbits (Himalayan allele) & Siamese cats: darker extremities due to lower temperature • Many Drosophila melanogaster wing mutations Environmental effects on phenotype • Temperature, continued… • Sea turtles: sex is determined by temperature at which the egg is incubated • Warmer = female; cooler = male Environmental effects on phenotype • Nutrition • PKU: reduce protein intake, eliminate phenotype • Diabetes: reduce sugar intake or provide insulin, eliminate or reduce phenotype • Significant height increase in first generation Americans Environmental effects on phenotype • Drugs • Hemophilia: supply blood clotting factor, eliminate phenotype • Cocaine: may induce schizophrenia Environmental effects on phenotype • Environmental factors may produce mimics of genetic traits • phenocopies • thalidomide • 1950s treatment for morning sickness • produced phenocopy of phocomelia, “paddle limbs” • drug in use again for cancer, Hansen’s disease (leprosy) Environmental effects on phenotype • May modify effects of genotypes for good or bad • May mask genes or mimic genes • These phenotypic changes WILL NOT be passed on to offspring. Genotype not changed, just phenotype.