The binomial expansion and probability     A      a           A     a            A     a        A     a        A    aA    ...
• If an individual has a dominant phenotype  what is the genotype (AA or Aa)? - Do a testcross                           ...
Observed Ratios of Progeny                The Goodness-of-Fit Chi-Square Test• Observed ratio of progeny may deviate from ...
Observed Ratios of Progeny                    The Goodness-of-Fit Chi-Square Test    • The hypothesis that chance alone is...
Observed Ratios of Progeny                     The Goodness-of-Fit Chi-Square Test• If we cross 2 heterozygous black (Bb X...
Observed Ratios of Progeny      The Goodness-of-Fit Chi-Square Test                    X2 = 6• Then we figure-out the degr...
Table 3.5             The probability of the event due to chance decreases      When value is less than 0.05, chance is no...
Chapter 4   Sex Determination          andSex-Linked Characteristics
Chapter 4 Outline  4.1 Sex Is Determined by a Number of Different   Mechanisms, 74  4.2 Sex-Linked Characteristics Are D...
Sex Determination           • Sexual reproduction is having offspring           that are genetically different from parent...
Sex Determination                • Usually, females have XX and males XY                • Some rare males have XX sex chro...
Sex determination                                   Overview• Sex determination = Process by which an organism differentia...
Major modes of sex determination                     Involvement of sex chromosomes• Discovery of chromosomes involved in ...
Major modes of sex determination                      Involvement of sex chromosomes• Discovery of chromosomes involved in...
Major modes of sex determination                     Involvement of sex chromosomes- Males are not always the heterogameti...
Major modes of sex determination                    Beyond the sex chromosomes• Haplodiploidy (bees, ants, wasps)  - Have ...
Sex determination in humans• Sex determination in humans        -individuals with abnormal combinations of sex chromosomes...
The Role of Sex                     Chromosomes1) You need X!      - At least one X to develop into a human.2) If you have...
Alterations of sex chromosome number                                    How does it occur?• Several conditions exist in wh...
Alterations of sex chromosome number                          How does it occur?• How do individuals obtain an abnormal # ...
Alterations of sex chromosome number                                           The disorders• Results of nondisjunction in...
Alterations of sex chromosome number                                  The disorders• Lets examine the conditions caused by...
Alterations of sex chromosome number                              The disorders2) Klinefelter syndrome (XXY)     - Individ...
Klinefelter syndrome (XXY)http://www.youtube.com/user/paulawaziry?feature=mhee#p/c/C038F6E6BFE2738A/27/coGty5bqs4A get cor...
Alterations of sex chromosome number                              The disorders3) Triplo X syndrome (XXX) or Poly-X female...
Sex ratios in the human population                                 Is it 50-50?• In theory:   - Half of a males gametes sh...
The “Y” to become a man• Y chromosome is extremely small – was thought to be genetically empty  - In recent years, scienti...
The Y chromosome                            Becoming a man2) Nonrecombining region of the Y (NRY) – rest of the Y   - This...
The Y chromosome                              Becoming a manNonrecombining region of the Y (NRY)  - This can be divided in...
Extensions of Mendel                                Sex-linked genes• See different inheritance patterns if genes are loca...
Extensions of Mendel                               Sex-linked genes• How do we know which genes are on the sex (X and Y) c...
X-linked Color Blindness in Humans• The color blindness gene is recessive (b). The normal gene is dominant (B).           ...
X-linked Color Blindness in HumansQ: Betty has normal vision, but her mother is color blind. Bill is color blind. If Bill ...
Dosage compensation                                  Inactivating X• Since human females have 2 X chr. and males have 1, f...
Dosage compensation                               Inactivating X• How does X inactivation occur?  - A region of the X chro...
Chapter 5 Outline 5.1 Additional Factors at a Single Locus Can Affect the Results of  Genetic Crosses, 100 5.2 Gene Inte...
Benjamin A. Pierce                               GENETICS         A Conceptual Approach                                 ...
5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses Multiple alleles: For a given locus, m...
5.1 Additional Factors at a Single Locus CanAffect the Results of Genetic Crosses Genes at the same locus - two versions ...
Extensions of Mendel                 Incomplete dominance and codominance                              X• Incomplete domin...
Extensions of Mendel      Incomplete dominance and codominance• Codominance  - Both alleles are dominant (neither backs do...
Extensions of Mendel• Dependency of Type of Dominance on Level of Pheno Observed  - Both alleles are expressed (neither ba...
Extensions of Mendel                                         Lethal alleles• Lethal alleles – Their presence results in de...
Extensions of Mendel                           Lethal alleles• Lethal alleles – Their presence results in death of the org...
Extensions of Mendel                       Lethal alleles• Lethal alleles  2) Dominant lethal alleles (e.g. Huntington)   ...
5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses Penetrance : the percentage of individ...
Extensions of Mendel                          Penetrance vs. expressivity• Two individuals with the same genotype can have...
Extensions of Mendel                         Penetrance vs. expressivity• Two individuals with the same genotype can have ...
Concept Check 1 Assume that long fingers are inherited as a recessive trait with 80% penetrance. Two people heterozygous f...
Concept Check 1 Assume that long fingers are inherited as a recessive trait with 80% penetrance. Two people heterozygous f...
Concept Check 2 A cross between two green corn plants yields 2/3 progeny that are green and 1/3 progeny that are white.  ...
Concept Check 2 A cross between two green corn plants yields 2/3 progeny that are green and 1/3 progeny that are white.  ...
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 ...
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 ...
5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single               Phenotype• Gene interaction: ...
Extensions of Mendel                  Polygenic inheritance - Epistasis• A gene is not a hermit!!!                        ...
Extensions of Mendel                          Polygenic inheritance - Epistasis• Epistasis  Specific case of polygenic in...
Extensions of Mendel                       Polygenic inheritance - Epistasis• Epistasis  Specific case of polygenic inher...
Extensions of Mendel                        Polygenic inheritance - Epistasis• Epistasis examples  - Set-up    - Genes A a...
Extensions of Mendel                                                                       DONT                        Pol...
Concept Check 4     A number of all-white cats are crossed and they     produced the following types of progeny: 12/16 all...
5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single               Phenotype• Complementation: D...
Complementation analysis                Determining how many genes affect a given trait• Complementation analysis – Experi...
Complementation analysis                Determining how many genes affect a given trait• If you mate 2 mutant flies togeth...
Extensions of Mendel                 Sex-influenced and sex-limited traits5.3 Influences the inheritance and expression of...
5.3 Sex Influences the Inheritance andExpression of Genes in a Variety of Ways.  Genetic maternal effect  Genomic imprin...
Extensions of Mendel           Sex-influenced and sex-limited traits How the sex of an individual can influence theexpres...
Extensions of Mendel                  Sex-influenced and sex-limited traits• Example: Male-pattern baldness  - Controlled ...
Extensions of Mendel                 Mitochondrial inheritance and maternal effect• Mitochondrial genome is very different...
• Mechanisms for mtDNA inheritance include(A) dilution: an egg has 100,000 to 1,000,000 mtDNA molecules, versus    100 to ...
Extensions of Mendel                                 Penetrance vs. expressivity• Cytoplasmic Inheritance: chloroplasts/ m...
Extensions of Mendel             Mitochondrial inheritance and maternal effect• Genetic maternal effect  - Proteins in the...
Extensions of Mendel                     Penetrance vs. expressivity• Some factors that affect penetrance/expressivity of ...
Extensions of Mendel                   Penetrance vs. expressivity- Imprinting- Males and females do not contribute the sa...
Extensions of Mendel                             Penetrance vs. expressivity- ImprintingEX: 1) Prader-Willi Syndrome: chil...
Genetics  lecture 2 pw_2012
Genetics  lecture 2 pw_2012
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Genetics lecture 2 pw_2012

  1. 1. The binomial expansion and probability A a A a A a A a A aA AA Aa A AA Aa A AA Aa A AA Aa A AA Aaa Aa aa a Aa aa a Aa aa a Aa aa a Aa aa n Here is where the Pascal’s triangle is useful…. (p+q) 0 (p+q) 1 1 1p + 1q (p+q) 2 1 p2 + 2 p1q1 + 1 q2 (p+q) 3 1 p3 + 3p2q1 + 3p1q2 + 1 q3 (p+q) 4 (p+q) 1 p4 + 4p3q1 + 6p2q2 + 4p1q3 + 1 q4 5 (p+q) 1 p5 + 5p4q1 + 10p3q2 + 10p2q3 + 5 p1q4 + 1 q5 6 (p+q) 1 p6 +6p5q1 + 15p4q2 + 20p3q3 + 15p2q4 + 6p1q5 + 1q6
  2. 2. • If an individual has a dominant phenotype  what is the genotype (AA or Aa)? - Do a testcross A A• Testcross a Aa Aa - Take your individual in question and mate with a homozygous recessive (aa): a Aa Aa - Predictions: 1) If the individual is AA AA x aa  all offspring should have A a DOMINANT phenotype a Aa aa 2) If the individual is Aa Aa x aa  1/2 should have dom. pheno a Aa aa 1/2 should have rec. pheno.  Routinely done to determine the genotype of an individual
  3. 3. Observed Ratios of Progeny The 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 roaches…There 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 values It indicates the probability that the difference between observed and expected values is due to chance.
  4. 4. Observed Ratios of Progeny The Goodness-of-Fit Chi-Square Test • The hypothesis that chance alone is responsible for any deviation between 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 Bbb Bb bb
  5. 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: B b Black kittens expected: (3/4) of 50 = 37.5B BB Bbb Bb bb Grey kittens expected: (1/4) of 50 = 12.5 S (observed – expected) 2 Chi-Square value = X2 = expected (30 – 37.5) 2 (20 – 12.5) 2 X2 = + X2 = 6 37.5 12.5
  6. 6. Observed Ratios of Progeny The Goodness-of-Fit Chi-Square Test X2 = 6• Then we figure-out the degrees of freedom = n-1n = the number of ways that things can vary in the cats‟ case: it‟s “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. 7. Table 3.5 The probability of the event due to chance decreases When value is less than 0.05, chance is not responsible for this! Solve Problem 35 at the end of chapter 3
  8. 8. Chapter 4 Sex Determination andSex-Linked Characteristics
  9. 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. 10. Sex Determination • Sexual reproduction is having offspring that are genetically different from parents • Meiosis produces haploid gametes • fertilization produces diploid 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. 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 chromosome…Sex determination and chromosomal changes
  12. 12. Sex determination Overview• Sex determination = Process by which an organism differentiates into one of two distinguishable sexes (some variations here)• Some terms related to sex determination: 1) Autosomes – Chromosomes not directly involved in the determination of sex 2) Sex chromosomes – Chromosomes that directly help determine sex 3) Primary sexual differentiation – Formation of the gonads 4) 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 organs 6) 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. 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 X chromosome - 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 a second 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. 14. Major modes of sex determination Involvement of sex chromosomes• Discovery of chromosomes involved in sex determination - In both of the above examples, the male ultimately determines the sex of offspring 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-up and 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. 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, it‟s the genes on the sex chromosomes that are important for sex determination In all 3 modes of sex determination just discussed, sex is also INFLUENCED by genes in the autosomes - e.g. SOX9 (chr. 17) – Transcription factor involved in male gonad development
  16. 16. Major modes of sex determination Beyond 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 between sisters 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 males and 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 incubate determines the sex of the organism
  17. 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, even if that person has 2 X chromosomes
  18. 18. The Role of Sex Chromosomes1) You need X! - At least one X to develop into a human.2) If you have Y, you‟re a male!3) Genes affecting fertility are located in both Y and X chrom. - A female needs at least 2 X‟s to be fertile.4) Additional X‟s may upset normal development in both - Additional X‟s produce physical and mental problems that are proportional to the # of X‟s.
  19. 19. Alterations of sex chromosome number How does it occur?• Several conditions exist in which individuals contain an abnormal number of 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. 20. Alterations of sex chromosome number How does it occur?• How do individuals obtain an abnormal # of sex chromosomes? - Nondisjunction!
  21. 21. Alterations of sex chromosome number The disorders• Results of nondisjunction in the sex chromosomes: XX XX XX meiosis X X XX XXfertilization X Y X X Y Y XX XY XXX Triplo X XO Turner XXY XYO Normal situation Klinefelter Death syndrome syndrome syndrome
  22. 22. Alterations of sex chromosome number The disorders• Lets examine the conditions caused by having an abnormal number 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 normal http://www.youtube.com/watch?v=ldjb-FR-PKo&feature=related
  23. 23. Alterations of sex chromosome number The 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 their testes are underdeveloped and fail to produce sperm (they are sterile) - Are usually very tall, with long arms and legs - Have several feminine characteristics including enlarged breasts, rounded hips, and sparse hair - Can give regular testosterone shots to reduce feminine characteristics (but still sterile)
  24. 24. Klinefelter syndrome (XXY)http://www.youtube.com/user/paulawaziry?feature=mhee#p/c/C038F6E6BFE2738A/27/coGty5bqs4A get correct link
  25. 25. Alterations of sex chromosome number The 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 symptoms 4) 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. 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 higher mortality 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. 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 the Y chromosome (as many as 350)• Several distinct regions of the Y chromosome have been identified: 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 patterns of inheritance as genes located on the autosomes - Men are diploid for those genes, unlike all other genes on X and Y
  28. 28. The Y chromosome Becoming 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 transcribed b) Euchromatin – Active areas that contain genes that are constantly being transcribed - A section of this euchromatin near the PAR on the p 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. 29. The Y chromosome Becoming 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 mouse embryos that are XX causes all embryos to develop into males - Euchromatin contains many other genes - Some have homologs on X and appear to play no direct role in sex determination (expressed in many tissues) - Others are believed to play a role in male fertility - Mutations in these genes often cause male sterility
  30. 30. Extensions of Mendel Sex-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 on Gene located on a sex chromosome the X chromosome E E female XE XE e Ee Ee Xe XEXe XEXe male e Ee Ee Y XEY XEY All F1 (male and female) All F1 (male and female) are heterozygous and have have red eyes red eyes
  31. 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 generation Gene not located on Gene located on a sex chromosome the X chromosome E e female XE Xe E EE Ee XE XEXE XEXe male e Ee ee Y XEY XeY See a 3:1 ratio of red to white 100% of females have red eyes in the F2 – no pattern for males 50% of males have red, 50% white and females Some X-linked human disorders Color blindness, muscular dystrophy, and hemophilia (all are recessive)
  32. 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 chromosome Normal Color blind XB XB Xb Xb XB Xb Xb Y XB Xb XB Y XB XBXB XBXbQ: If you have a boy that is color blind,and parents who are normal, what is Y XBY XbYthe genotype of the mother? She is a hererozygous / carrier
  33. 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? Yes Gene located on 2) Draw possible genotypes: the X chromosome Normal Color blind XB XB Xb Xb Xb XB XB Xb Xb Y XB Y Xb XBXb XbXb 3) Betty (with normal vision) is a carrier (mom is color blind) Y XBY XbY 4) Bill is color blind 5) Probability for child to be color blind: (1/4)+(1/4)=1/2 or 50%
  34. 34. Dosage compensation Inactivating X• Since human females have 2 X chr. and males have 1, females should have twice the 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 female embryo 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 observed as 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. 35. Dosage compensation Inactivating X• How does X inactivation occur? - A region of the X chromosome called the X-inactivation center (XIC) is required 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 somehow prevents 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. 36. Chapter 5 Outline 5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses, 100 5.2 Gene Interaction Takes Place When Genes at Multiple Loci Determine a Single Phenotype, 106 5.3 Sex Influences the Inheritance and Expression of Genes in a Variety of Ways, 115 5.4 Anticipation Is the Stronger or Earlier Expression of Traits in Succeeding Generations, 122 5.5 The Expression of a Genotype May Be Affected by Environmental Effects, 123
  37. 37. Benjamin A. Pierce GENETICS A Conceptual Approach  FOURTH EDITION CHAPTER 5 Extensions and Modifications of Basic Principles© 2012 W. H. Freeman and Company
  38. 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. 39. 5.1 Additional Factors at a Single Locus CanAffect the Results of Genetic Crosses Genes at the same locus - two versions of the same gene; each version of the same gene is defined as allele.  Fig. 5.2  Incomplete dominance  Codominance  Table 5.1
  40. 40. Extensions of Mendel Incomplete dominance and codominance X• 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. 41. Extensions of Mendel Incomplete 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. 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 LOCUS http://www.youtube.com/watch?v=r7HP0whUMbE&feature=rel
  43. 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 aaLethal F fhttp://www.youtube.com/watch?v=SeoPF74QSms - Example: Mating two green corn plants yields F FF Ff 2/3 green progeny and 1/3 white progeny. How? - Good example of AA and Aa having diff. phenotypes f Ff ff 2) 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. 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 aaLethalhttp://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) F f F FF Ff f Ff ff
  45. 45. Extensions of Mendel Lethal alleles• Lethal alleles 2) 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 Aa a Aa aa
  46. 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. 47. Extensions of Mendel Penetrance 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. 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. 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. 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? ¼ X 80% = 20%
  51. 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 white progeny?
  52. 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 white progeny? White genotype: GG; Green genotype: Gg gg: lethal allele causing death in homozygous.
  53. 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. 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. 55. 5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single Phenotype• Gene interaction: Effects of genes at one locus depend on the presence of genes at other loci. – Gene interaction that produces novel phenotypes. • Fig. 5.7 – Gene interaction with epistasis • Epistasis: one gene masks the effect of another gene.
  56. 56. Extensions of Mendel Polygenic inheritance - Epistasis• A gene is not a hermit!!! • It will often interact with others.
  57. 57. Extensions of Mendel Polygenic inheritance - Epistasis• Epistasis  Specific case of polygenic inheritance in which one gene interferes with 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 epistasis 1) 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. 58. Extensions of Mendel Polygenic inheritance - Epistasis• Epistasis  Specific case of polygenic inheritance in which one gene interferes with 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. 59. Extensions of Mendel Polygenic 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 AaBb A a B b - Possible genotypes A AA Aa B BB Bb A_B_ 9/16 aaB_ 3/16 a Aa aa b Bb bb A_bb 3/16 aabb 1/16 - Phenotypic ratios if epistasis 1) Recessive epistasis (assume aa is epistatic to gene B) A_B_ 9/16  Black If have "aa", gene B doesnt matter A_bb 3/16  Brown  Get 9:3:4 ratio for this cross aaB_ 3/16  Albino aabb 1/16  Albino
  60. 60. Extensions of Mendel DONT Polygenic inheritance - Epistasis MEMORIZE NUMBERS!!• Epistasis examples - Phenotypic ratios if epistasis 2) 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  Black A_bb 3/16  Albino If have either aa or bb, the other gene doesnt aaB_ 3/16  Albino matter aabb 1/16  Albino  Get 9:7 ratio for this cross 4) Duplicate domiant epistasis (A_ and B_can block the other) A_B_ 9/16  Albino A_bb 3/16  Albino If have either A_ or B_, the other gene doesnt aaB_ 3/16  Albino matter aabb 1/16  Black  Get 15:1 ratio for this cross
  61. 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. BbAa A_B_ 9/16 c. B_A_ Albinod. B_aa A_bb 3/16  Albino aaB_ 3/16  Black aabb 1/16  Brown
  62. 62. 5.2 Gene Interaction Takes Place WhenGenes At Multiple Loci Determine a Single Phenotype• Complementation: Determine whether mutations are at the same locus or at different loci.
  63. 63. Complementation analysis Determining 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 1 fly 2 X X X X X A B A B wingless wingless Each of the offspring get 1 good copy of gene A and 1 good copy of gene B All F1 offspring X  The 2 genes complement each other X A B WINGS!!
  64. 64. Complementation analysis Determining 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 1 fly 3 X X X X X A B A B wingless wingless Each of the offspring get All F1 offspring 2 bad copies of A X  NO complementation!! X A B All flies that fail to complement wingless one another have mutations in the same gene
  65. 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. 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. 67. Extensions of Mendel Sex-influenced and sex-limited traits How the sex of an individual can influence theexpression of genes on: 1) autosomal chromosomes 2) characteristics determined by genes in the cytoplasm 3) characteristics for which maternal genotype determines phenotype of offspring 4) expression of autosomal genes and how it is affected by the sex of the parent from whom the gene was inherited.
  68. 68. Extensions of Mendel Sex-influenced and sex-limited traits• Example: Male-pattern baldness - Controlled by an autosomal enzyme that converts testosterone to DHT (Dihydrotestosterone) - DHT alters gene expression in the scalp  Baldness - Females have little testosterone - May make enzyme, but lack of testosterone makes it quiet.
  69. 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 has 1000s 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. 70. • Mechanisms for mtDNA inheritance include(A) dilution: an egg has 100,000 to 1,000,000 mtDNA molecules, versus 100 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. 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. 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. 73. Extensions of Mendel Penetrance vs. expressivity• Some factors that affect penetrance/expressivity of a gene 3) Epigenetics - Methylation can shut down gene expression without 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. 74. Extensions of Mendel Penetrance vs. expressivity- Imprinting- Males and females do not contribute the same genetic material to the offspring- Autosomal genes – long assumed to have equal effects on gene expression- However, the expression of some genes is significantly affected by the parental origins- There are several human disorders associated with imprinting:EX) Prader-Willi and Angelman Syndromes
  75. 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 mother’schrom.• Frequent laughter• Uncontrolled muscle movement• Large mouth• Unusual seizures

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