1. The binomial expansion and probability Aa A aA aA aAaAAAAa A AAAa A AAAa A AAAa A AA AaaAaaa a Aaaa a Aaaa a Aaaa a Aa aa n Here is where the Pascals triangle is useful. (p+q)0(p+q)11 1p + 1q(p+q)21 p2 + 2 p1q1 + 1 q2(p+q)31 p3 + 3p2q1 + 3p1q2 + 1 q3(p+q)4(p+q)1 p4 + 4p3q1 + 6p2q2 + 4p1q3 + 1 q45(p+q) 1 p5 + 5p4q1 + 10p3q2 + 10p2q3 + 5 p1q4 + 1 q56(p+q) 1 p6 +6p5q1 + 15p4q2 + 20p3q3 + 15p2q4 + 6p1q5 + 1q6

2. If an individual has a dominant phenotype what is the genotype (AA or Aa)? - Do a testcrossAA Testcrossa AaAa- Take your individual in question and matewith a homozygous recessive (aa): aAaAa - Predictions: 1) If the individual is AA AA x aa all offspring should have A aDOMINANT phenotype a Aa aa 2) If the individual is AaAa x aa 1/2 should have dom. pheno a Aaaa1/2 should have rec. pheno. Routinely done to determine the genotype of an individual 3. Observed Ratios of ProgenyThe Goodness-of-Fit Chi-Square Test Observed ratio of progeny may deviate from expected ratios by chance.We expected a 1:1 ratio, but after counting Yellow and Brown roachesThere were 22 Brown and 18 Yellow So when do we use the Chi-Square Test? When what comes out is not what we expected!To see how well observed values FIT the expected valuesIt indicates the probability that the difference between observedand expected values is due to chance. 4. Observed Ratios of ProgenyThe Goodness-of-Fit Chi-Square Test The hypothesis that chance alone is responsible for any deviationbetween observed and expected values is called the null hypothesis . Looking at the cats: Black (B) is dominant over Gray (b) If we cross 2 heterozygous black (Bb X Bb), we would expect a 3:1 ratio:B b Now we have 50 kittens: 30 black and 20 grayB BB BbbBb bb 5. Observed Ratios of Progeny The Goodness-of-Fit Chi-Square Test If we cross 2 heterozygous black (Bb X Bb), we would expect a 3:1 ratio: Observed values: 50 kittens: 30 black and 20 gray First get the expected values: Bb Black kittens expected: (3/4) of 50 = 37.5BBBBbbBbbbGrey kittens expected: (1/4) of 50 = 12.5S(observed expected) 2 Chi-Square value = X2 =expected(30 37.5) 2 (20 12.5) 2X2 =+X2 = 637.512.5 6. Observed Ratios of ProgenyThe Goodness-of-Fit Chi-Square TestX2 = 6 Then we figure-out the degrees of freedom = n-1n = the number of ways that things can vary in the cats case: its 2 phenotypes degrees of freedom = 2-1 = 1 Now we look at the CHI table and see where 6 is For a degree of fredom = 1 7. Table 3.5 The probability of the event due to chance decreasesWhen value is less than 0.05, chance is not responsible for this!Solve Problem 35 at the end of chapter 3 8. Chapter 4 Sex DeterminationandSex-Linked Characteristics 9. Chapter 4 Outline 4.1 Sex Is Determined by a Number of Different Mechanisms, 74 4.2 Sex-Linked Characteristics Are Determined by Genes on the Sex Chromosomes, 81 10. Sex Determination Sexual reproduction is having offspring that are genetically different from parents Meiosis produces haploid gametes fertilization producesdiploid zygotes Q: What is the fundamental difference between males and females? A: Gamete size, of course! However We define the sex of an individual in reference to its phenotype 11. Sex Determination Usually, females have XX and males XY Some rare males have XX sex chromosomes- With a piece of the Y chrom. (SRY) attached to some other chromosomeSex determination and chromosomal changes 12. Sex determination Overview Sex determination = Process by which an organism differentiates into one oftwo distinguishable sexes (some variations here) Some terms related to sex determination:1) Autosomes Chromosomes not directly involved in the determination of sex2) Sex chromosomes Chromosomes that directly help determine sex3) Primary sexual differentiation Formation of the gonads4) Secondary sexual differentiation Formation of all other visible traits that are indicative of a given sex (facial hair, genitalia, etc.)5) Unisexual Individuals who have only male OR female reproductive organs6) Bisexual/hermaphroditic Individuals who contain both male AND female sex organs Pre-conceived notions from human genetics:- XX is always female, XY is always male- Sexual reproducing species have male members and female members- The bulk of the organism is diploid, gametes are haploid Not the case for all species 13. Major modes of sex determination Involvement of sex chromosomes Discovery of chromosomes involved in sex determination- Earliest studies were in insects called Protenor- Female somatic cells = 14 chromosomes, including 2 X chromosomes- All female gametes have 7 chromosomes (1 X)- Male somatic cells = 13 chromosomes, including just 1 Xchromosome - Half of the male gametes get 7 chromosomes (w/ X) and half have 6 (w/o X) Thus, sex in this species is determined by the presence or absence of asecond X chromosome (called the XX/XO mode of sex determination)- Subsequent studies were done in insects called Lygaeus turicus- Both females and males have 14 chromosomes- Both have 12 autosomes- Females have 2 X chromosomes- Males have 1 X chromosome and a smaller chromosome called Y Thus, sex in this species is determined by the presence of 2 of the same sex chromosomes or 2 different (heterophilic) sex chromosomes (called the XX/XY mode of sex determination) 14. Major modes of sex determinationInvolvement of sex chromosomes Discovery of chromosomes involved in sex determination- In both of the above examples, the male ultimately determines the sex ofoffspring because they produce 2 types of gametes (X or no X, X or Y) - They are called the heterogametic sex - Females of these species are thus said to be the homogametic sex Q: Since the X and Y chromosomes are not homologous, how do they pair-upand segregate in meiosis? A: The X and Y chrom. are homologous in small regions called PSEUDOAUTOSOMAL regions. In these regions, both X and Y carry the same genes. TIPs: In humans, there are pseudoautosomal regions at the tips: 15. Major modes of sex determination Involvement of sex chromosomes- Males are not always the heterogametic sex- In many species (moths, butterflies, most birds, some fish, reptiles, amphibians), the female is the heterogametic sex- Often use the notation ZZ/ZW for these species (ZW females, ZZ males) Keep in mind that the chromosomes themselves do nothing, its the genes onthe sex chromosomes that are important for sex determination In all 3 modes of sex determination just discussed, sex is also INFLUENCEDby genes in the autosomes - e.g. SOX9 (chr. 17) Transcription factor involved in male gonad development 16. Major modes of sex determinationBeyond the sex chromosomes Haplodiploidy (bees, ants, wasps)- Have no sex chromosomes- Sex is determined by the number of chromosome sets found in the nuclei- Males develop from unfertilized eggs (HAPLOID)Females develop from fertilized eggs (DIPLOID) Average genetic relatedness betweensisters in this system is 75% (instead of usual 50%)- Maybe why these species are known for cooperation Genic sex determination (some plants and protozoans) - No obvious differences between chromosomes of malesand females (same number, type) - Sex is determined by several different genes found on the autosomes Environment controlled sex determination (some reptiles)- Environment partly or fully controls sex determination- Example: Temperature at which reptile embryos incubatedetermines the sex of the organism 17. Sex determination in humans Sex determination in humans-individuals with abnormal combinations of sex chromosomes - XXY and XO Will they be female or male? Phenotypically normal?- Results (more later about these syndromes): - XXY male characteristics, but with developmental problems(having an extra X is bad for some reason) - XO female characteristics, but with developmental problems(we need to have 2 sex chromosomes The Y chromosome actively tells a human to become a male, evenif that person has 2 X chromosomes 18. The Role of Sex Chromosomes1) You need X!- At least one X to develop into a human.2) If you have Y, youre a male!3) Genes affecting fertility are located in both Y and X chrom. - A female needs at least 2 Xs to be fertile.4) Additional Xs may upset normal development in both - Additional Xs produce physical and mental problems that are proportional to the # of Xs. 19. Alterations of sex chromosome numberHow does it occur? Several conditions exist in which individuals contain an abnormal numberof sex chromosomes - Individuals look like one of 2 sexes, but have various developmental abnormalities How do individuals obtain an abnormal of sex chromosomes? - First, a review of meiosis http://highered.mcgraw- hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535:: 535::/sites/dl/free/0072437316/120074/bio16.swf: :Unique%20Features%20of%20Meiosis http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter12/animations.html# 20. Alterations of sex chromosome numberHow does it occur? How do individuals obtain an abnormal # of sex chromosomes? - Nondisjunction! 21. Alterations of sex chromosome number The disorders Results of nondisjunction in the sex chromosomes:XXXX XXmeiosisXX XX XXfertilization XYXX Y Y XXXY XXX Triplo X XOTurnerXXYXYONormal situationKlinefelter Deathsyndrome syndrome syndrome 22. Alterations of sex chromosome numberThe disorders Lets examine the conditions caused by having an abnormalnumber of sex chromosomes: 1) Turner syndrome (XO)- Individuals have only 1 X chromosome (and no Y) - Most die during embryonic development- Female genitalia and ducts, but infertile- Have short stature, underdeveloped feminine traits, low hair line, broad chest and webbed neck - Intelligence usually normalhttp://www.youtube.com/watch?v=ldjb-FR-PKo&feature=related 23. Alterations of sex chromosome numberThe disorders2) Klinefelter syndrome (XXY) - Individuals have at least 2 X chromosomes to go along with at least 1 Y chr.- XXY (most common), XXXY, XXYY, XXXXY, XXXYY- Have male genitalia and internal ducts, but theirtestes are underdeveloped and fail to producesperm (they are sterile) - Are usually very tall, with long arms and legs- Have several feminine characteristics includingenlarged breasts, rounded hips, and sparse hair - Can give regular testosterone shots to reducefeminine characteristics (but still sterile) 24. Klinefelter syndrome (XXY)http://www.youtube.com/user/paulawaziry?feature=mhee#p/c/C038F6E6BFE2738A/27/coGty5bqs4A get correct link 25. Alterations of sex chromosome numberThe disorders3) Triplo X syndrome (XXX) or Poly-X females- Females that have at least 1 extra X chromosome - XXX, XXXX, XXXXX- Highly variable phenotype - Some women are normal, some have several mental impairment,some are infertile - The more Xs, the worse the symptoms4) XYY (superman or supervillain) - Very controversial condition (was taken out of the book) - Scientists hypothesized that such individuals may be overly aggressive and have behavioral problems - End result: Having an extra Y chromosome (most likely) does not make you more prone to aggressive behavior- They did find that men with XYY are taller than average (usually over 6) 26. Sex ratios in the human population Is it 50-50? In theory: - Half of a males gametes should contain an X chr. and half a Y chr. Equal numbers of males and females should be conceived and born Studies in the 1940s and 60s showed the following:- Primary sex ratio = ratio of males/females CONCEIVED = ~1.40 - More males are conceived than females. However, male fetuses have a highermortality rate (how do we know this)- Secondary sex ratio = ratio of males/females BORN = ~1.05 - Still more males are born, but not as great a difference as indicated by the primary ratio Any of the above assumptions could be incorrect, leading to these differences- One idea: Sperm carrying Y has less mass than 1 carrying X. More motile? - the X sperm is more resistant (survives longer) 27. The Y to become a man Y chromosome is extremely small was thought to be genetically empty- In recent years, scientists have found several genes located throughout theY chromosome (as many as 350) Several distinct regions of the Y chromosome have beenidentified:1) Pseudoautosomal regions (PARs)- Homologous region exists on the X chromosome- PARs on X and Y contain homologous genes- Allows the Y chromosome to pair up with the X chr.during prophase I (allows for crossing over with X)- Critical for proper segregation of X/Y during meiosis- Genes found in the PAR region exhibit similar patternsof inheritance as genes located on the autosomes - Men are diploid for those genes,unlike all other genes on X and Y 28. The Y chromosomeBecoming a man2) Nonrecombining region of the Y (NRY) rest of the Y - This can be divided into several sub-regions: a) Heterochromatin Lacks "functional" genes- Stays hypercondensed in interphase(when transcription should be occurring)- Genes, if present, will never be transcribedb) Euchromatin Active areas that contain genes that are constantly being transcribed - A section of this euchromatin near the PAR on thep arm contains a critical gene that controls male development (not found on X)- Called the Sex determining region of Y (SRY)- SRY encodes a protein called testis-determining factor (TDF) - TDF Binds to DNA and causes it to bend (only known function)- Present in all male mammals (critical evolutionarily speaking) 29. The Y chromosomeBecoming a manNonrecombining region of the Y (NRY)- This can be divided into several subregions:b) Euchromatin - How do they know the SRY has this function?- Some human males that have 2 Xs and no Y - SRY was abnormally transferred to one of the Xs- Some human females are XY - The SRY in the Y chr. has been deleted- Transferring just the SRY gene into mouseembryos that are XX causes all embryos todevelop into males- Euchromatin contains many other genes- Some have homologs on X and appear to play no direct role in sexdetermination (expressed in many tissues)- Others are believed to play a role in male fertility- Mutations in these genes often cause male sterility 30. Extensions of MendelSex-linked genes See different inheritance patterns if genes are located on the X or Y chr. - Females XX, males XY- If a gene is on the X chromosome, males can only be hemizygous- Example: Dominant allele of a gene causes fruit flies to have red eyes (E) and a recessive form (e) causes them to have white eyes.- Imagine that we cross a pure bred red-eyed female and a white-eyed male Gene not located onGene located on a sex chromosome the X chromosome E E femaleXEXE eEeEeXeXEXe XEXemale eEeEe YXEY XEYAll F1 (male and female)All F1 (male and female) are heterozygous and havehave red eyesred eyes 31. Extensions of Mendel Sex-linked genes How do we know which genes are on the sex (X and Y) chromosomes?- Lets look at the F2 generationGene not located onGene located ona sex chromosome the X chromosomeE efemaleXEXeEEEEeXE XEXE XEXe maleeEe ee YXEY XeY See a 3:1 ratio of red to white 100% of females have red eyesin the F2 no pattern for males50% of males have red, 50% whiteand females Some X-linked human disorders Color blindness, muscular dystrophy, and hemophilia (all are recessive) 32. X-linked Color Blindness in Humans The color blindness gene is recessive (b). The normal gene is dominant (B). Gene located onQ: What is the genotype of normal females and males? the X chromosomeNormal Color blindXB XBXb XbXB XbXb Y XBXbXB Y XB XBXB XBXbQ: If you have a boy that is color blind,and parents who are normal, what isYXBY XbYthe genotype of the mother?She is a hererozygous / carrier 33. X-linked Color Blindness in HumansQ: Betty has normal vision, but her mother is color blind. Bill is color blind. If Bill andBetty have a child, what is the probability that the child will be color blind?A: 1) Is it sex-linked? YesGene located on 2) Draw possible genotypes:the X chromosome NormalColor blind XB XB Xb Xb Xb XB XB Xb Xb Y XB YXb XBXb XbXb 3) Betty (with normal vision) is a carrier(mom is color blind)YXBY XbY 4) Bill is color blind 5) Probability for childto be color blind:(1/4)+(1/4)=1/2 or 50% 34. Dosage compensationInactivating X Since human females have 2 X chr. and males have 1, females should have twicethe amount of proteins that are encoded by genes located on the X chr. - Furthermore, women that are XXX should have 3 times the amount - NOT THE CASE! Early in embryonic development (~ 8 cell stage), each cell in the femaleembryo will randomly inactivate 1 of its X chromosomes - Each cell derived from those original 8 will have the same inactivation pattern - Example: If X chr. 1 is inactivated in cell #4, all cells derived from #4 will have X chr. 1 inactivated The inactivated X chr. becomes highly condensed and is observedas a dark spot at the edge of the nucleus (during interphase)- Called a Barr body So, why is having XXY or XXX harmful?- Possible that having an extra X is bad early in development- Possible that part of the X is still active (near PARs) 35. Dosage compensation Inactivating X How does X inactivation occur?- A region of the X chromosome called the X-inactivation center (XIC) isrequired for X chr. inactivation - XIC contains a gene that is transcribed produces a transcript called X-inactive specific transcript (Xist) - Xist is only produced from the X chromosome that will be inactivated- Xist is not produced from the active X chromosome- Xist is never translated into protein- Xist RNA is thought to form a coat around the X chr. and somehowprevents acetylation, induces methylation, ...... What dont we know? - In cases of XXY or XXX, how do cells count how many Xs should be inactivated? - What prevents the production of Xist from the "good" X chromosome? - How do progeny cells keep the same pattern of X inactivation? Does it stick with the chromosomes during replication and mitosis? 36. Chapter 5 Outline 5.1 Additional Factors at a Single Locus Can Affect the Results ofGenetic Crosses, 100 5.2 Gene Interaction Takes Place When Genes at Multiple LociDetermine a Single Phenotype, 106 5.3 Sex Influences the Inheritance and Expression of Genes in aVariety of Ways, 115 5.4 Anticipation Is the Stronger or Earlier Expression of Traits inSucceeding Generations, 122 5.5 The Expression of a Genotype May Be Affected byEnvironmental Effects, 123 37. Benjamin A. Pierce GENETICS A Conceptual Approach FOURTH EDITION CHAPTER 5 Extensions and Modificationsof Basic Principles 2012 W. H. Freeman and Company 38. 5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses Multiple alleles: For a given locus, more than two alleles are present within a group of individuals. Fig. 5.5 ABO blood group Fig. 5.6 39. 5.1 Additional Factors at a Single Locus CanAffect the Results of Genetic Crosses Genes at the same locus - two versions of thesame gene; each version of the same gene isdefined as allele. Fig. 5.2 Incomplete dominance Codominance Table 5.1 40. Extensions of Mendel Incomplete dominance and codominanceX Incomplete dominance (more like the blending) - Neither allele is dominant - Heterozygotes look like an intermediate between homozygotes - They have a different phenotype than either homozygote - Example: Red snapdragons x white snapdragons Pink snapdragons - RR x WW RWImportant: It affects the phenotype, but not the way in which genes are inherited. 41. Extensions of MendelIncomplete dominance and codominance Codominance- Both alleles are dominant (neither backs down)- Heterozygotes look like a combination of homozygotes- They possess both phenotypes of the homozygotes- Examples: Sickle-cell disease and ABO blood type Type A Type B Type AB Type O (IAIA or IAi) (IBIB or IBi)(IAIB) (ii) 42. Extensions of Mendel Dependency of Type of Dominance on Level of Pheno Observed- Both alleles are expressed (neither backs down)- Case of cystic fibrosis - Caucasian disorder - usually recessive disease - production of thick, sticky mucus: clogs pancreas ducts; and airways- Gene on long arm of Chr.7 - Cystic Fibrosis Transmembrane conductance Regulator - CFTR - regulates movement of Cl- ionsIf heterozygous, there is codominance at molecular level;However, normal Cl- transport;Physiological level: mutated allele appearsTo be recessive. DOMINANCE = ALLELIC INTERACTION GENES AT THE SAME LOCUShttp://www.youtube.com/watch?v=r7HP0whUMbE&feature=rel 43. Extensions of Mendel Lethal alleles Lethal alleles Their presence results in death of the organism- Many are embryonic lethal individual is never born Most lethal alleles are recessive, but some are dominant1) Recessive lethal alleles (e.g. Tay Sachs kills before age 3) - Two copies of allele needed for lethality - AA/Aa Normal aaLethalFfhttp://www.youtube.com/watch?v=SeoPF74QSms - Example: Mating two green corn plants yieldsF FF Ff 2/3 green progeny and 1/3 white progeny. How? - Good example of AA and Aa having diff. phenotypes f Ff ff2) Dominant lethal alleles (e.g. Huntington) - Only one copy needed for lethality http://www.youtube.com/watch?v=MRZoM5L5dak - AA/Aa Lethal aa Normal (Dominant isnt always better!!) - Can only pass on to kids if reproduce before it kills - Example: Huntingtons Disease - Doesnt kill until age >30 - If it killed at age 2, could an Aa person pass it on? 44. Extensions of Mendel Lethal alleles Lethal alleles Their presence results in death of the organism- Many are embryonic lethal individual is never born Most lethal alleles are recessive, but some are dominant1) Recessive lethal alleles (e.g. Tay Sachs usually kills before age 3) - Two copies of allele needed for lethality - AA/Aa Normal aaLethalhttp://www.youtube.com/watch?v=SeoPF74QSms - Example: Corn: Mating two green corn plants yields 2/3 green progeny and 1/3 white progeny. How? - Good example of AA and Aa having diff. phenotypes (also example of incomplete dominance)FfFFFFffFfff 45. Extensions of Mendel Lethal alleles Lethal alleles2) Dominant lethal alleles (e.g. Huntington) - Only one copy needed for lethalityhttp://www.youtube.com/watch?v=MRZoM5L5dak AA/Aa Lethal aa Normal (Dominant isnt always better!!) - Can only pass on to kids if reproduce before it kills - Huntingtons Disease doesnt kill until age >30 - If it killed at age 2, could an aa person pass it on? A a A AA Aaa Aaaa 46. 5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses Penetrance : the percentage of individuals having a particular genotype that express the expected phenotype. Expressivity: The degree to which a characteristic is expressed. 47. Extensions of MendelPenetrance vs. expressivity Two individuals with the same genotype can have different phenotypes- More than genotype affects phenotype- Nature vs. nurture Penetrance vs. expressivity - Penetrance = Frequency, under a given environmental condition, with which a specific phenotype is observed by individuals with a specific genotype - If only 10% of individuals have expected phenotype low penetrance- Phenotype is affected by other things - If 95% of individuals have expected phenotype high penetrance- Genotype has dominant effect on phenotypeEX: 42 people have the allele, but only 38 express the gene.Penetrance = 38/42 = 0.9 = 90% 48. Extensions of Mendel Penetrance vs. expressivity Two individuals with the same genotype can have different phenotypes- More than genotype affects phenotype- Nature vs. nurture - Expressivity = The range of different phenotypes observed for a given genotype - Example: Polydactyly in humans - Child 1: Only a little slab of skin (low expressivity) - Child 2: Fully functional extra digit(s) (high expressivity) THE PHENOTYPE IS SHOWING = with penetrance HOW IS IT SHOWING? = expressivity 49. Concept Check 1 Assume that long fingers are inherited as a recessive trait with 80% penetrance. Two people heterozygous for long fingers mate. What is the probability that their first child will have long fingers? 50. Concept Check 1 Assume that long fingers are inherited as a recessive trait with 80% penetrance. Two people heterozygous for long fingers mate. What is the probability that their first child will have long fingers? X 80% = 20% 51. Concept Check 2 A cross between two green corn plants yields 2/3 progeny that are green and 1/3 progeny that are white. What is the genotype of the green progeny and the whiteprogeny? 52. Concept Check 2 A cross between two green corn plants yields 2/3 progeny that are green and 1/3 progeny that are white. What is the genotype of the green progeny and the whiteprogeny?White genotype: GG;Green genotype: Gggg: lethal allele causing death in homozygous. 53. Concept Check 3 What blood types are possible among the children of a cross between a man who is blood-type A and a woman of blood-type B? 54. Concept Check 3 What blood types are possible among the children of a cross between a man who is blood-type A and a woman of blood-type B?Could be: A type with a genotype of IAIA and IAi; Could be B type with a genotype of IBIB or IBi Could be AB type with a genotype of IAIB Could also be a O type with a genotype of ii 55. 5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single Phenotype Gene interaction: Effects of genes at onelocus depend on the presence of genes atother loci. Gene interaction that produces novelphenotypes. Fig. 5.7 Gene interaction with epistasis Epistasis: one gene masks the effect of anothergene. 56. Extensions of MendelPolygenic inheritance - Epistasis A gene is not a hermit!!! It will often interact with others. 57. Extensions of MendelPolygenic inheritance - Epistasis Epistasis Specific case of polygenic inheritance in which one gene interfereswith the expression of a totally different gene- Gene A blocks the effect of gene B on the phenotype- Example: Gene A leads to hair production, Gene B leads to hair color- What would happen if gene A were defective? Different types of epistasis1) Recessive epistasis - Two recessive alleles of gene a blocks gene B - If have "aa", doesnt matter what gene B is. 2) Dominant epistasis- One dominant allele of gene A blocks gene B- If have "A_", doesnt matter what gene B is. 58. Extensions of Mendel Polygenic inheritance - Epistasis Epistasis Specific case of polygenic inheritance in which one gene interfereswith the expression of a totally different gene- Gene A blocks the effect of gene B on the phenotype- Example: Gene A leads to hair production, Gene B leads to hair color- What would happen if gene A were defective? EPISTATIC(cont.)3) Duplicate recessive epistasis- Two genes can block each other ("aa" can block B and "bb" can block A)4) Duplicate dominant epistasis("A_" can block B and "B_" can block A) 59. Extensions of MendelPolygenic inheritance - Epistasis Epistasis examples- Set-up- Genes A and B contribute to color an animal (black, brown, albino)- Defining albino as a lack of color (yellow labrador example)- Mating AaBb x AaBbAa B b - Possible genotypes A AAAa B BBBb A_B_ 9/16 aaB_ 3/16a Aaaa b Bbbb A_bb 3/16 aabb1/16 - Phenotypic ratios if epistasis 1) Recessive epistasis (assume aa is epistatic to gene B)A_B_ 9/16 BlackIf have "aa", gene B doesnt matterA_bb 3/16 Brown Get 9:3:4 ratio for this crossaaB_ 3/16 Albinoaabb1/16 Albino 60. Extensions of Mendel DONTPolygenic inheritance - Epistasis MEMORIZE NUMBERS!! Epistasis examples- Phenotypic ratios if epistasis2) Dominant epistasis (assume A_ is epistatic to gene B) A_B_ 9/16 Albino A_bb 3/16 Albino If have "A_", gene B doesnt matter aaB_ 3/16 Black Get 12:3:1 ratio for this cross aabb 1/16 Brown 3) Duplicate recessive epistasis (aa and bb can block the other)A_B_ 9/16 BlackA_bb 3/16 Albino If have either aa or bb, the other gene doesntaaB_ 3/16 Albino matteraabb1/16 Albino Get 9:7 ratio for this cross 4) Duplicate domiant epistasis (A_ and B_can block the other)A_B_ 9/16 AlbinoA_bb 3/16 AlbinoIf have either A_ or B_, the other gene doesntaaB_ 3/16 Albinomatteraabb1/16 Black Get 15:1 ratio for this cross 61. Concept Check 4 A number of all-white cats are crossed and they produced the following types of progeny: 12/16 all- white; 3/16 black; and 1/16 gray. What is the genotype of the black progeny?a. Bbb. BbAaA_B_ 9/16 c. B_A_ Albinod. B_aaA_bb 3/16 AlbinoaaB_3/16 Blackaabb 1/16 Brown 62. 5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single Phenotype Complementation: Determine whether mutationsare at the same locus or at different loci. 63. Complementation analysisDetermining how many genes affect a given trait Complementation analysis Experiment used to determinehow many genes affect a given trait If you mate 2 mutant flies together, you would expect to see the following:1) If the 2 flies have mutations in different genes (non-allelic)fly 1fly 2 X XX X XABABwinglesswinglessEach of the offspring get1 good copy of gene A and1 good copy of gene BAll F1 offspring X The 2 genes complementeach other X A B WINGS!! 64. Complementation analysisDetermining how many genes affect a given trait If you mate 2 mutant flies together, you would expect to see the following:2) If the 2 flies have mutations in the same gene (allelic)fly 1fly 3X XXX XABABwinglesswinglessEach of the offspring get All F1 offspring2 bad copies of A X NO complementation!! X ABAll flies that fail to complementwinglessone another have mutations inthe same gene 65. Extensions of Mendel Sex-influenced and sex-limited traits5.3 Influences the inheritance and expression of genes in a variety of ways.Some traits are observed largely in one sex over another despite beingcontrolled by an autosomal gene - If MOSTLY in one sex = Sex-influenced (higher penetrance in one sex) if ONLY in one sex = Sex-limited (no penetrance in the other sex) - Usually due to differences in sex hormone production 66. 5.3 Sex Influences the Inheritance andExpression of Genes in a Variety of Ways. Genetic maternal effect Genomic imprinting : differential expression of genetic material depending on whether it is inherited from the male or female parent. Epigenetics: Phenomena due to alterations to DNA that do not include changes in the base sequence; often affect the way in which the DNA sequences are expressed. 67. Extensions of Mendel Sex-influenced and sex-limited traits How the sex of an individual can influence theexpression of genes on:1) autosomal chromosomes2) characteristics determined by genes in the cytoplasm3) characteristics for which maternal genotype determines phenotype of offspring4) expression of autosomal genes and how it isaffected by the sex of the parent from whom thegene was inherited. 68. Extensions of MendelSex-influenced and sex-limited traits Example: Male-pattern baldness- Controlled by an autosomal enzyme that converts testosterone toDHT (Dihydrotestosterone)- DHT alters gene expression in the scalp Baldness- Females have little testosterone- May make enzyme, but lack of testosterone makes it quiet. 69. Extensions of Mendel Mitochondrial inheritance and maternal effect Mitochondrial genome is very different from the nuclear genome- All genes on a single circular chromosome- Each mitochondrion has several copies, each cell has1000s of mitochondria High copy number- Only passed from mom offspring- Most genes encode either tRNAs or cellular respiration proteins Mitochondrial genome is not diploid, but not quite haploid- Every cell has a mixture of mitochondrial genomes- Lots of variability due to high copy number Mitochondrial inheritance is very complicated!! 70. Mechanisms for mtDNA inheritance include(A) dilution: an egg has 100,000 to 1,000,000 mtDNA molecules, versus100 to 1000 on a sperm,(B) Degradation of sperm mtDNA in the fertilized egg;(C) Failure of sperm mtDNA to enter the egg.Whatever the mechanism, this pattern of mtDNA inheritance is found in mostanimals, most plants and in fungi as well. 71. Extensions of Mendel Penetrance vs. expressivity Cytoplasmic Inheritance: chloroplasts/ mitochondria - mtDNA is inherited from the mother (maternally inherited). - mitochondrial diseases are inherited from the mother.Ex: Leber Hereditary Optic Neuropathy (LHON)Rapid loss of vision in both eyes resulting from death of cells in opticnerve. Onset ~ 20 24 yearshttp://www.youtube.com/watch?v=RQLdKEaExRA&feature=related 72. Extensions of Mendel Mitochondrial inheritance and maternal effect Genetic maternal effect- Proteins in the moms egg play a major role in embryonic development - Moms genotype solely determines phenotype of her offspring - No role of dads or offsprings DNA - Mutate moms DNA mutant egg protein mutant develop. 73. Extensions of Mendel Penetrance vs. expressivity Some factors that affect penetrance/expressivity of a gene 3) Epigenetics - Methylation can shut down gene expressionwithout altering genotype- Imprinting is good example, where the information in certain genesis active only when it passes to a child through the sperm or the egg. - The system of being stamped according to the paternal or maternal originof a gene copy All affect gene expression (transcription levels)while having no effect on DNA sequence 74. Extensions of Mendel Penetrance vs. expressivity- Imprinting- Males and females do not contribute the same genetic material tothe offspring- Autosomal genes long assumed to have equal effects on geneexpression- However, the expression of some genes is significantly affectedby the parental origins- There are several human disorders associated with imprinting:EX) Prader-Willi and Angelman Syndromes 75. Extensions of Mendel Penetrance vs. expressivity- ImprintingEX: 1) Prader-Willi Syndrome: child is missing a small region on thelong arm of chrom. 15 that was inherited from the father. Small hands and feet Short stature Poor sexual development Mental retardation Frequently obesehttp://www.youtube.com/user/paulawaziry?feature=mhee#p/c/C038F6E6BFE2738A/5/X-QAIO3t41UEX: 2) Angelman Syndrome:Same region of chrom. 15 is missing, but now from the motherschrom. Frequent laughter Uncontrolled muscle movement Large mouth Unusual seizures