MIC150 - Chap 2 Extension Of Mendelian Genetics

1. EXTENSION OF MENDELIAN GENETICS Codominance Incomplete dominance Multiple alleles Lethal alleles Epistasis Polygenic inheritance Linked genes Crossover values and gene mapping Sex linked genes

2. INTRODUCTION Mendelian inheritance describe patterns that obey two laws Law of segregation Law of independent assortment Includes simple Mendelian inheritance A single gene with two different alleles Alleles display a simple dominant/recessive relationship

3. INTRODUCTION ( cont ) Simple Mendelian inheritance Traits affected by a single gene Two alleles exist for this gene 3:1 phenotypic ratio in the F 2 generation

4. INTRODUCTION ( cont ) Dominant alleles are usually indicated either by: an italic uppercase letter ( D ) Recessive alleles are usually indicated either by: an italic lowercase letter ( d ) If no dominance exists, italic uppercase letters and superscripts are used to denote alternative alleles ( R 1 , R 2 , C W , C R ).

5. MENDELIAN INHERITANCE 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 .

6. MENDELIAN INHERITANCE ( cont ) Wild-type alleles (dominant) are the most prevalent alleles in a population Encoded protein is generally Functional Made in the proper amount Confer various phenotypes e.g., Purple flowers, round seeds, etc.

7. MENDELIAN INHERITANCE ( cont ) Mutant alleles (recessive) have been altered by mutation Tend to be rare in natural populations Commonly defective in ability to express functional protein Encoded protein is often: Produced in reduced amount (decreased synthesis) Less functional (decreased function) Often inherited in a recessive fashion Confer various phenotypes e.g., White flowers, wrinkled seeds, etc.

8. MENDELIAN INHERITANCE ( cont ) Genetic disease are caused by mutant alleles In many human genetic diseases, the recessive allele contains a mutation. What kind of genetic disease that you know of containing recessive alleles? (submit in two weeks time)

9. MENDELIAN INHERITANCE ( cont ) Simple dominant/recessive relationship Fairly common among many genes One copy of the dominant allele is sufficient to produce the dominant phenotype Recessive allele does not affect the phenotype of heterozygotes

10. Production of functional protein is reduced by 50% 50% is adequate to provide a normal phenotype Homozygotes produce more wild-type protein than necessary

11. LETHAL ALLELES Gene is an essential for survival An estimated 1/3 of all genes are essential for survival Mutant allele is a lethal allele Has potential to cause death I nherited in a recessive manner Absence of a specific protein may result in a lethal phenotype

12. LETHAL ALLELES ( cont ) Many lethal alleles prevent cell division These will kill an organism at an early age However, some lethal alleles exert their effect later in life e.g. Huntington disease causes a progressive degeneration of the nervous system Age of onset is generally 30 – 50 Progressive degeneration of nervous system, dementia and early death

13. LETHAL ALLELES ( cont ) Some lethal alleles exert their effect only under certain environmental conditions “ Conditional lethal alleles ” e.g., Temperature-sensitive ( ts ) lethals May kill developing Drosophila larva at 30 o C Larva will survive if grown at 22 o C Why do you think this is the case? (submit in two weeks time)

14. LETHAL ALLELES ( cont ) Two types of Lethal alleles Dominant lethal alleles Recessive lethal alleles

15. Dominant LA The LA modify the 3:1 phenotypic ratio into 1:1 The individuals with a dominant LA die before they can produce the progeny. Therefore, the mutant dominant LA is removed from the population in the same generation in which it arose. Huntington’s disease is caused by a dominant LA and even though it is not described as lethal, it is invariably lethal in that the victim experiences gradual neural degeneration for some years before death occurs.

16. Recessive LA They maybe of two kinds (i) one which has no obvious phenotypic effect in heterozygotes and (ii) one which exhibit a distinctive phenotype when in heterozygous condition. Recessive LA don’t cause death in the heterozygous form because a certain threshold of protein output is maintained. In the homozygous form, the protein output doesn’t meet the threshold, causing death. Eg diseases; cystic fibrosis, Tay- S achs disease, sickle cell anemia , and brachydactyly .

17. brachydactyly

18. Recessive LA ( cont ) One coat colour of ranch foxes is caused by recessive lethal gene. This gene causes a death if both recessive alleles are possessed by the same individual. It occasionally arise by mutation from a normal allele. However, in many cases lethal genes became operative at time the individual become sexually mature. Complete lethality, thus is the case where no individual of a certain genotype attain the age of reproduction.

19. LETHAL ALLELES ( cont ) Lethal alleles may produce ratios that seemingly deviate from Mendelian ratios e.g., “Creeper” phenotype in chickens Shortened wings and legs Creeps rather than walking normally Creeper chicken are heterozygous Creeper Cp - shortlegged ,  - autosomal semi-lethal incomplete dominant

20. All “creeper” birds are heterozygous Creeper x Normal 1:1 phenotypic ratio Creeper phenotype is dominant Creeper x creeper  2:1 Creeper allele is a recessive lethal Creeper homozygotes are dead

21. TWO ALLELES Codominance Incomplete Dominance

22. CODOMINANCE Any given gene may have more than two alleles and the phenotype of both alleles are in heterozygote. Two alleles are expressed Do not blend the phenotype ‘Co’ – means together Co-dominance = both alleles are dominant Example: different blood types and group antigens

23. Also an example of multiple alleles, will be explain further later

24. CODOMINANCE ( cont ) Different from Segregation Law As both of the alleles are dominant, we are going to use ‘R’ for the colour of cow’s hair R R = all red hair R W = all white hair R R R W = red and white hair R R R R x R W R W = 100% R R R W

25. INCOMPLETE DOMINANCE Heterozygotes sometimes display a phenotype intermediate between the homozygotes e.g., Flower color in the four-o’clock, snapdragons, carnations, etc. Homozygous red ( C R C R ) x homozygous white ( C W C W ) F 1 offspring ( C R C W ) are heterozygous and pink F 2 offspring display 1:2:1 phenotypic and genotypic ratios

26. 50% of the CR protein is not sufficient to produce the red phenotype 1:2:1 phenotypic ratio but NOT the 3:1 ratio observed as in simple Mendelian Inheritance

27. Many traits appear to be dominant Closer examination shows that some are actually incompletely dominant e.g., Seed shape in Mendel’s peas RR and Rr genotypes produce round seeds rr genotypes produces wrinkled seeds Decreased starch deposition

28. EXERCISE Predict the phenotype ratios of offspring when a homozygous white cow is crossed with a roan (red and white) bull. What is the phenotypes and genotypes for parent cattle be if a farmer wanted only cattle with red fur? A cross between a black cat and a tan cat produces a tabby pattern (black and tan fur together) a) What pattern of inheritance does this illustrate? b) What is the percentage of kittens will have tan fur if a tabby cat is crossed with a black cat?

29. THREE ALLELES Multiple alleles

30. MULTIPLE ALLELES Individuals possess two copies of each gene At most, they possess two different alleles Means there are same/more than three alleles The situation exclude the dominant and recessive effects All the alleles show own effects in inheritance Eg . Blood type and hair colour

31. MULTIPLE ALLELES ( cont ) Coat color in rabbits is determined by alleles of the “C” gene Four different alleles exist C = full coat color c ch = chinchilla c h = himalayan c = albino Any particular rabbit possesses only two alleles

32. MULTIPLE ALLELES ( cont ) Dominant/recessive relationships between coat color alleles C is dominant to c ch , c h , and c c ch is recessive to C , but dominant to c h , and c c h is recessive to C and c ch , but dominant c c is recessive to C , c ch , c h C > c ch > c h > c

33. MULTIPLE ALLELES ( cont ) Four different alleles C (full coat color) c ch (Chinchilla - partial defect in coloration) c h ( himalayan - pigmentation only in certain parts) Temperature-sensitive conditional allele c (albino- is a defective allele producing no protein necessary for pigment production)

34. This is caused by tyrosinase ; producing melanin Eumelanin : black pigment and phaeomelanin (orange/yellow pigment)

35. MULTIPLE ALLELES ( cont ) c ch c  x  Cc h Genotypes: 1 Cc ch    :1 Cc  : 1 C ch c h  : 1 c h c Phenotypes: 2 Full: 1 Chinchilla: 1Himalayan c ch c C Cc ch Cc c h C ch c h c h c

36. CONDITIONAL ALLELES c h is a temperature-sensitive conditional allele Results in pigmentation only in certain parts of the body Encoded enzyme functions only in cooler areas of the body Ends of extremities, tail, paws, nose, ears Similar temperature-sensitive alleles are found in other animals e.g., Siamese cat

37. MULTIPLE ALLELES ( cont )

38. MULTIPLE ALLELES ( cont ) Red blood cells contain carbohydrate chains on their plasma membranes “Antigens” Recognized by immune system’s antibodies A, B, and O antigens determine human blood type Synthesized by three alleles of a single gene I A , I B , and i

39. MA: RED BLOOD CELLS What are antigens? (submit in two weeks time)

40. The “i” gene produces an enzyme Glycosyl transferase Attaches sugar “branches” to carbohydrate “trees” present on the surface of red blood cells i allele encodes a defective enzyme No sugar branches are attached I A and I B alleles encode enzymes with different substrate specificities Different sugar “branches” are attached

41. MA: RED BLOOD CELLS ( cont ) i is recessive to both I A and I B ii  type O blood I A and I B are codominant I A I B  AB blood Possesses both A and B antigens

42. MA: RED BLOOD CELLS ( cont ) Blood typing is essential for safe blood transfusions The donor’s blood must be an appropriate match with the recipient’s blood Eg . If a type O individual received blood from a type A, type B or type AB blood Antibodies in the recipient blood will react with antigens in the donated blood cells Donated blood will agglutinate Life threatening situation: clogging vessels

43. EXERCISE Cross a heterozygous type A with a heterozygous type B. 1. ___ I A i ____  X  ____ I B i ___ 2. ___ I A I B ____  X  ____ ii ___ What is the genotypes and phenotypes?

44. EXERCISE A woman with type O blood and a man who is type AB are expecting a child. What are the possible blood type of the kid? What are the possible blood type of a child who’s parents are both heterozygous for ‘B’ blood type? Jill is blood type O. She has two brothers (who always tease her) with blood type A and B. What are the genotypes o f her parents with respect to this traits?

45. Continue….

46. GENES COMPLEX INTERACTION Epistasis Polygenic Inheritance

47. EPISTASIS Defined as: An inheritance pattern in which the alleles of one gene mask the phenotypic effects of the alleles of another genes

48. EPISTASIS Epistasis , first defined by the English geneticist, William Bateson in 1970, is the masking of the expression of a gene at one position in a chromosome, or locus, at one or more genes at other position. Epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes .

49. EPISTASIS (cont) The genes whose phenotype is expressed is said to be epistatic , while the phenotype altered or suppressed is said to be hypostatic. Epistasis can be contrasted with dominance, which is an interaction between alleles at the same gene locus. Epistasis is often studied in relation to Quantitative Trait Loci (QTL) and polygenic inheritance

50. Example: Walnut Comb rr and pp to be epistatic to this phenotype. rr and pp mask a walnut comb.

51. F 2 PR Pr pR pr PR PPRR PPRr PpRR PpRr Pr PPRr PPrr PpRr Pprr pR PpRR PpRr ppRR ppRr pr PpRr Pprr ppRr pprr P 1      Pea Comb X Rose Comb PPrr       ppRR   F 1       All Walnut Combs PpRr   When these F 1  birds are crossed, all four phenotypes are observed:  

52. Ratio Description Name(s) of Relationship  (Used by Some Authors) 9:3:3:1 Complete  dominance  at both  gene  pairs; new phenotypes result from  interaction  between  dominant  alleles, as well as from interaction  between both  homozygous  recessives Not named because the ratio looks like independent assortment 9:4:3 Complete  dominance  at both  gene  pairs; however, when 1 gene  is  homozygous   recessive , it hides the  phenotype  of the other gene Recessive   epistasis 9:7 Complete  dominance  at both  gene  pairs; however, when either gene  is  homozygous   recessive , it hides the effect of the other gene Duplicate  recessive   epistasis 12:3:1 Complete  dominance  at both  gene  pairs; however, when one gene  is  dominant , it hides the  phenotype  of the other  gene Dominant   epistasis 15:1 Complete  dominance  at both  gene  pairs; however, when either gene  is  dominant , it hides the effects of the other  gene Duplicate  dominant   epistasis 13:3 Complete  dominance  at both  gene  pairs; however, when either gene  is  dominant , it hides the effects of the other  gene Dominant  and  recessive   epistasis 9:6:1 Complete  dominance  at both  gene  pairs; however, when either gene  is  dominant , it hides the effects of the other  gene Duplicate  interaction 7:6:3 Complete  dominance  at one  gene  pair and partial  dominance  at the other; when  homozygous   recessive , the first gene is epistatic to the second  gene No name 3:6:3:4 Complete  dominance  at one  gene  pair and partial  dominance  at the other; when  homozygous   recessive , either gene hides the effects of the other  gene ; when both genes are  homozygousrecessive , the second gene hides the effects of the first No name 11:5 Complete  dominance  for both  gene  pairs only if both kinds of dominant  alleles are present; otherwise, the  recessivephenotype  appears No name

53. POLYGENIC INHERITANCE This term is use to refer to inheritance of quantitative traits, traits which are influenced by multiple genes and not just one. Because many traits are spread out across the continuum, rather than being divided into black and white differences, polygenic inheritance helps to explain the way in which these traits are inherited and focused. A related concept is pleiotropy , an instance where one gene influences multiple traits (phenotypes).

54. However, in the 20 th century, people were well aware that most traits are too far complex to be determined by a single gene, and the idea of polygenic inheritance was born.

55. POLYGENIC INHERITANCE ( cont ) One easily understood example of polygenic inheritance is height . People are not just short or tall; they have a variety of heights which run along a spectrum . Furthermore, height is also influenced by environment ; someone born with tall genes could become short due to malnutrition or illness , for example, while someone born with short genes could become tall through genetic therapy.

56. POLYGENIC INHERITANCE ( cont ) Basic genetics obviously wouldn't be enough to explain the wide diversity of human heights, but  polygenic inheritance shows how multiple genes in combination with a person's environment can influence someone's phenotype, or physical appearance.

57. POLYGENIC INHERITANCE ( cont ) Polygenic traits are a result of additive effects of contribution of each genes in loci and therefore they do not follow typical dominance and recessive patterns. The second aspect of polygenic genes are, the traits are determined by environmental variations . It means that an individual can be genetically same, but can differ in their physical appearance.

58. POLYGENIC INHERITANCE ( cont ) P henotypes like high blood pressure (hypertension) are not the result of a single "blood pressure" gene with many alleles (a 120/80 allele, a 100/70 allele, a 170/95 allele, etc.) The phenotype is an interaction between a person's weight (one or more obesity genes), cholesterol level (one or more genes controlling metabolism), kidney function (salt transporter genes), smoking (a tendency to addiction), and probably lots of others too. Each of the contributing genes can also have multiple alleles. 

59. Skin colour is another example of polygenic inheritance, as are many congenital diseases. Because polygenic inheritance is so complex, it can be a very absorbing and frustrating field of study. Researchers may struggle to identify all of the genes which play a role in a particular phenotype, and to identify places where such genes can go wrong. However , once researchers do learn more about the circumstances which lead to the expression of particular traits, it can be a very rewarding experience.

60. DON’T GET CONFUSED! Multiple alleles=more than two forms of the same gene in the population e.g blood type Polygenic traits=more than one gene contributes to the phenotype 

61. POLYGENIC INHERITANCE ( cont ) Examples in Humans Weight Height Eye colour Intelligence Behaviour Skin colour

62. In pleiotropy , on the other hand,  one  gene is responsible for multiple things. Several congenital syndromes are examples of pleiotropy , in which a flaw in one gene causes widespread problems for a person.

63. For example, sickle cell  anemia  is a form of pleiotropy , caused by a distinctive mutation in one gene which leads to a host of symptoms. In addition to causing mutations, pleiotropy also occurs in perfectly normal genes, although researchers tend to use it to track and understand mutations in particular.

64. LINKED GENES The dihybrid cross we previously did assumed the genes were on different pairs of chromosomes. Now , we want to look at an example where the genes involved are on the same chromosome.

65. LINKED GENES ( cont ) One such example is the flower colour and pollen shape experiment done by  Bateson  and  Punnett . In the plants that they studied, the genes for pollen shape and flower colour are located on the same chromosome (pair) as each other, thus are inherited together .

66. Dihybrid cross Linked genes cross

67. If the parents are  PPLL  ×  ppll , the first parent will only make gametes with  PL  and the second with  pl , which doesn't seem too different so far. From these parents, the F 1  generation would all be  PpLl .

68. However, when calculating what the F 2  generation will be, since the genes are located on the same pair of chromosomes, then theoretically, the only possible gametes are  PL  and  pl  (not  Pl  or  pL ). The phenotype ratio for this cross is 3:1 , not 9:3:3:1 as would be expected for a “normal” dihybrid cross. Because these genes are on the same chromosome pair, they are called  linked genes . PL pl PL PPLL PpLl pl PpLl ppll

69. SEX LINKED GENES This is  sex-linked genes , genes located on  one  of the sex chromosomes (X or Y) but not the other. Since , typically the X chromosome is longer, it bears a lot of genes not found on the Y chromosome, thus most sex-linked genes are  X-linked genes .

70. One example of a sex-linked gene is fruit fly eye colour . An X chromosome carrying a normal, dominant, red-eyed allele would be symbolized by a plain  X , while the recessive, mutant, white-eyed allele would be symbolized by  X'  or  X w . A fly with genotype XX' would normally be a female with red eyes, yet be a  carrier  for the white-eyed allele. Because a male typically only has one X chromosome, he would normally be either XY and have normal, red eyes, or X'Y and have white eyes. The only way a female with two X chromosomes could have white eyes is if she would get an X' allele from both parents making her X'X' genotype. The cross between a female carrier and a red-eyed male would look like this: X Y X XX XY X’ XX’ X’Y

71. SEX LINKED GENES ( cont ) Typically, X-linked traits show up more in males than females because typical XY males only have one X chromosome, so if they get the allele on their X chromosome, they show the trait. If a typical XX female is a carrier, 50% of her sons will get that X chromosome and show the trait. In order for an XX female to exhibit one of these X-linked traits, most of which are recessive mutations , she would have to have two copies of the allele (X'X'), which would mean that her mother would have to be a carrier and her father have the trait so she could get one allele from each of them.

72. The Punnett square would predict that ½ of their sons (¼ of their children) would be hemophiliacs and ½ of their daughters (¼ of their children) would be carriers. Their children married other royalty, and spread the gene throughout the royal families of Europe.

73. SEX LINKED GENES ( cont ) SEX LIMITED TRAIT Affects a structure or function of the body that is present in only male or only female E.g. Growth of beard or breast SEX INFLUENCED TRAIT An allele that is dominant in one sex and recessive in the other E.g. Baldness Heterozygous male is bald, heterozygous female is not

74. CROSSING OVER Even though the a lleles for different genes may be linked along the same chromosome, the linkage can be altered during meiosis. In diploid eukaryotic species, homologous chromosomes can exchange pieces with each other, a phenomenon called crossing over . This event occurs during prophase of meiosis I.

75. Combination alleles = genetic recombinant

76. Chiasma is the point where chromatids become criss-crossed and the chromosome exchange segements . New combinantion arise from crossing over resulting in recombination and passed during the gamete formation. When meiosis is over 2 chromosome separated to become individual chromatids and produce 4 genetically different chromosome.

77. GENE MAPPING Also known as chromosome mapping, to determine linear order and distance of separation among genes that are linked to each other along the same chromosome.

78. GENE MAPPING ( cont ) Why it is useful? Allow geneticist to understand overall complexity and genetic organization of a particular species. The genetic map of a species portrays underlying basis for the inherited traits that an organism display. Help in cloning process too

79. GENE MAPPING ( cont ) Genetic map benefits: Locate human gene that causing diseases, this information can be used to diagnose and someday treat inherited human diseases. Predict likelihood that a couple will produce children with certain inherited diseases. Also important in agriculture – help in improving crops/animal through selective breeding.

80. The End