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A Rap Tribute to Mendel • Check this out: Movie: http://www.youtube.com/watch?v=EvR_Sdm1orU http://history.nih.gov/exhibits/nirenberg/images/photos/01_mendel_pu.jpg Alleles Alter Phenotypes in Different Ways • Alternative forms of a gene are called alleles. • Mutation is the source of alleles. • The wild-type allele is the one that occurs most frequently in nature and is usually, but not always, dominant. • A mutation that results in a loss of function is called a null allele. • Phenotypic traits may be influenced by more than one gene (and associated alleles). Geneticists Use a Variety of Symbols for Alleles If wildtype is dominant: • Wildtype (dominant) e+ /e+ or e+/e (gray body) • Recessive (mutant) e (ebony body = mutant) If wildtype is recessive: • Mutant (dominant) Wr/Wr or Wr/Wr+ (both have wrinkled wings) • Wildtype (recessive) Wr+ / Wr+ (normal straight wings) • If no dominance exists, italic uppercase letters and superscripts are used to denote alternative alleles (R1, R2; CW, CR). Incomplete Dominance • In incomplete dominance, neither trait is dominant • Offspring from a cross with contrasting traits showing intermediate phenotype. •R1 = red allele R2 = white allele •Red snapdragons x white pink –R1R1 = red R2R2 = white R1R2 = pink •What are the genotypes of the F2 generation (so F1 pink) x F1 pink? Tay-Sachs Disease Incomplete Dominance • Double recessive offspring die w/in 3 years • Heterozygotes are phenotypically normal • Why is this an example of inc. dominance? A. Heterozygotes only produce about half of the normal enzymes coded by the dominant allele B. The mutant allele does not show up in the heterozygote individual C. The dominant allele masks any traits connected to the recessive allele Correct answer: A Tay-Sachs Disease Incomplete Dominance • Having one “good” allele insures that just enough gene product is produced to thwart off the genetic disorder. •The Threshold Effect for this disease is just under 50% of gene product production. Codominance: Both Alleles Influence Phenotype • In the heterozygote, gene products of both alleles can be detected. • One example is the MN blood group Two possible glycoproteins (antigens) attach to surface of red blood cells in humans. • If the 2 alleles are represented by LM and LN, what genotypes and phenotypes are possible? • If a man with this blood group, LMLN, had a child with a MLN, what are the odds that woman of this blood group, L Answer: their child would be of the M, LMLN, and LNLN Genotypes could be:MN LMLphenotype? A. 25% B. 50% C. 75% D. 100% Phenotypes could be: M, MN, and N Multiple Alleles of a Gene May Exist in a Population • Multiple alleles (>2) can be studied only in populations, because any individual will have at most + same gene. two alleles of the cn or wcn •3 or more alleles of the same gene •The ABO blood groups are an example of multiple alleles. w se or wse •Alleles: IA, IB, IO (or i) •Phenotypes: A, B, AB, or O 3 alleles for the ABO blood group • IA and IB alleles are codominant to each other • IA and IB alleles are dominant to the IO allele • The A antigen is made, the B antigen is made, both are made or neither is made. – Antigens are merely carbohydrate receptor sites on RBCs “A” carbohydrate (AcGalNH) “B” carbohydrate (galactose) The “H substance” Multiple Alleles: ABO Groups •With the ABO blood groups, how many genotypes are possible? Explain… A. 3 B. 4 C. 6 D. 9 Correct answer: C Solution: IAIO, IBIO, IAIA, IBIB, IAIB,& IOIO Multiple Alleles: ABO Groups • A baby was born with the O phenotype and the mother was type B. The husband was suspicious of the pregnancy and decided to have his blood group determined (IAIO). Should he be reassured by this information? Solution: The baby’s genotype has to be IOIO. The mother has to be IBIO . And so the baby is possibly his. Blood testing never proves it however… Calculating phenotypes with the blood groups • If a “B” phenotype male has kids with an “AB” phenotype female, what are the probable phenotypes for the kids? • IBIB x IAIB 50% “type A”, 50% “B” • IBIO x IAIB> 25% “A”, 50% “B”, 25% “AB” X-Linked Genes • Genes present on the X chromosome. • Males have only one X chromosome and therefore only one copy of the gene – Express whichever allele they get • Drosophila eye color was one of the first examples of Xlinkage. • If an X-linked allele is recessive and LETHAL before reproduction can occur, the disorder will occur only in males • Ex. Duchene muscular dystrophy & Lesch-Nyhan Syndrome No gene! Fly Cross #1 • How would you express the ratios of the F2 phenotypes? 2 red –eyed female: 1 red-eyed male: 1 white-eyed male Fly Cross #2 • How would you express the ratios of the F2 phenotypes? • Do the cross… Solution: 1 red eyed female: 1 white-eyed female: 1 red-eyed male: 1 white-eyed male Fly Cross #2 Solution • Question: Can a male inherit the gene for whiteeyes from his father? Answer: No, of course not! He has to inherit the Y chromosome from his dad. Color-blindness is X-linked • Review: Anthony’s Color-blindness.ppt • Check out: Ishihara Test for Color B.doc http://www.toledobend.com/colorblind/Ishihara.html • Check out: Seeing Color.doc http://askabiologist.asu.edu/research/seecolor/colortest.html • Look at: X-linked_traits.ppt for review Sex-limited Inheritance •Expression of a specific phenotype is absolutely limited to one sex. –Autosomal genes that are affected by sex hormones •In chickens, an autosomal gene controls feathering: Genotype HH Hh hh F phenotype Hen-like Hen-like Hen-like M phenotype Hen-like Hen-like Roster-like •Presence of F or M sex hormones makes the difference. Sex-influenced Inheritance • Sex of an individual influences the expression of a phenotype, but not limited to one sex or the other. • Male pattern baldness can happen in women, but its affect is usually less and happens later in life. Genotype BB Bb bb F phenotype Bald Not bald Not bald M phenotype Bald Bald Not bald Can Hair Loss be Treated? See a short movie… Male Pattern Baldness Can Hair Loss be Treated? See a short movie… Lethal Alleles • A loss of function mutation can sometimes be tolerated in the heterozygous state but may behave as a recessive lethal allele in the homozygous state. • Homozygous recessive individuals will not survive. • Heterozygotes may show a mutation in phenotype and it may be dominant over the wild type. – These alleles are generally very rare. • Ex. Coat color in mice (agouti is wildtype = A allele) Cross #1: agouti x agouti all agouti Cross #2: yellow x yellow 2/3 yellow; 1/3 agouti Cross #3: agouti x yellow 1/2 yellow; 1/2 agouti EXPLAIN??? Dominant Lethal Alleles •Sometimes mutation can be a dominant lethal allele. –Even a heterozygote will not survive. –One copy of the normal allele isn’t sufficient to reach the threshold level of the protein product • For dominant lethal alleles to persist in a population, individuals MUST be able to reproduce before dying. –Ex. Huntington’s Disease –H = dominant lethal allele; affected individuals are Hh •Disease does not become apparent until approx. age 40 •Famous folk singer Woody Guthrie died of this had this genetic disease and died at age 39 Combinations of Two Gene Pairs • Mendel’s independent assortment also governs 2 separate genes and respective alleles. • Consider this cross: Aa IAIB x Aa IAIB where allele “a” is a recessive trait for albinism. IAIB are the blood group alleles. • If these parents are crossed what is the most effective way for you to determine the possible phenotypes of the offspring? Solution: Must use the forked-line method and consider the outcomes of each gene separately… Combinations of Two Gene Pairs • Which of these statements is the right way to start? A. For the Aa x Aa cross, 3/4 of the offspring will be the normal, pigmented phenotype and ¼ will be albino. B. Take the Aa gene pair and combine it with the IAIB blood group to make a zygote. C. Realize that the A combines with the IA and the “a” combines with the IB . Correct answer: A. Epistasis • Many traits are actually affected by more than one gene. • One gene may mask the effect of another gene. or… • Two gene pairs may complement each other. –At least one dominant allele at each loci is needed or desirable product won’t be made. • Di-hybrid crosses typically yield the F2 phenotypic ratio of 9:3:3:1. If a cross yields some other ratio, epistasis is probably to blame. Epistasis and the Bombay Phenotype • Individuals appear to be type O blood group • Have rare recessive mutation: can’t make complete “H” substance (molecule on red blood cells). • Have working genes to make antigens A and/or B, but antigens can’t attach to “H”. –Phenotypically “O” blood; Genotypically IAIB • Conclusion: homozygous recessive condition (H mutation) masks gene expression at second locus (A and/or B antigen production). •H-substance gene is epistatic to the ABO antigen gene –Work out the following cross… IAIB Hh x IAIB Hh The H Substance • Normal Mutation Antigens: A and/or B Cell Normal “H” substance Cell Mutant “H” substance Conclusion? Antigens can’t attach. Appears as “no antigens”, type O Determine the Resulting Phenotypes • In mice, wildtype coloring is agouti (A). This is dominant to black (a). When homozygous (bb), a recessive mutation at a different loci eliminates color altogether resulting in albino mice. – It doesn’t matter what the genotype at the A loci is! Cross: Ratio 9/16 Genotype Phenotype A_B_ AaBb x AaBb 3/16 A_bb 3/16 aaB_ 1/16 aabb Five Cases of Epistasis Recessive epistasis (case 1), dominant epistasis (case 2), and complementary gene interaction (case 3). Figure 4-8 Copyright © 2006 Pearson Prentice Hall, Inc. Pleiotropy • Expression of a single gene has multiple phenotypic effects – This is quite common • Marfan syndrome dominant mutation resulting in defective fibrillin a common connective tissue protein • Can affect: eye lens, blood vessel lining, & bone formation. • Porphyria variegata don’t break down part of hemoglobin in red blood cells • Symptoms deep red urine, abdominal pain, headaches, insomnia, vision problems etc. Environmental Influences • Phenotypic expression of a trait may be influenced by environment as well as by genotype. • Temperature sensitive genes produce different phenotypes if the developmental temperature of tissue was is cool vs. warm. –Siamese cats: body parts such as tail, ears, and paws are all extremities and are “cooler” than core body parts. –In warm body parts, black pigment enzyme doesn’t function properly and no pigment (white) is produced. –The evening primrose is red when grown at 23oC & white at 18oC. Position Effect • Physical location of a gene may influence its expression due to a position effect. • Translocation or inversion of genes on a chromosome may affect position, and therefore expression of gene. Genes along a chromosome normal (top) translocation below Proximity to yellow gene may change blue gene expression Fruit fly Eye Mutation • Normal dominant phenotype showing brick-red eye color. • Variegated color caused by rearrangement of the “white” gene to another location in the genome. Figure 4-17 Copy right © 2006 Pearson Prentice Hall, Inc. Nutritional Mutations • May prevent the phenotype from reflecting the genotype. • Key nutrients are not made or can’t be broken down. • Supplements can overcome detrimental effect. •Ex. Phenylketonuria (PKU) –Mutation that prevents a person from metabolizing the amino acid phenylalanine. –Must eliminate that amino acid from their diet or complications, including brain damage result. –Babies are routinely “pricked” at birth to screen for this disorder. Lactose Intolerance • After maturing, the ability to produce an enzyme, lactase (which breaks down the milk sugar, lactose) often shuts down. • Milk intolerant people often have cramps, diarrhea, and bloating. • Yogurt, cheeses, butter low lactose alternatives • Lactase can also be purchased to alleviate symptoms.