Sex determination and sex linkage

1. Sex determination and sex linkage

2. Chromosomal Theory of Inheritance: simply states that chromosomes are carriers of genetic information (Walter Sutton)

3. Sex determination and sex linkage • Mendel was not the only one to make progress in the field of heredity. • In the early 1900s, Thomas Morgan made key discoveries regarding sex linkage and linked genes • In human cells, all chromosomes occur in structurally identical pairs except for two very important ones; the sex chromosomes, X and Y • Women have two structurally identical chromosomes. • Men have one X and one Y

4. Sex-linked traits • Morgan experimented with a quick breeding fruit fly species • The fruit flies had four pairs of chromosomes; three autosomal pairs and one sex chromosomes pair • An autosomal chromosome is one that is not directly involved in determining gender

5. Sex linked traits • In fruit flies, the more common phenotype for a trait is called the wild-type phenotype (e.g. red eyes) • Traits that are different from the normal are called mutant phenotypes (e.g. white eyes) Wild Type Mutant Type

6. Sex-linked Genes Sex Linked Genes Genes located on the X chromosome are inherited with that X. When doing crosses you must include the sex chromosomes in your cross. Use superscript letters for the allele. Example: In fruit flies, eye color is a sex linked trait. Red is dominant to white.  Females                Males X R X R                   X R  Y X R X r                     X r  Y X r X r FRUIT FLY CHROMOSOMESDrosophila melanogaster

7. Practice • Show the cross between a white eyed male and a red eyed female:  XrY x XRXR • Show the cross between a red eyed male and a white eyed female:

8. Were you correct?

9. Morgan’s crosses • Morgan crossed a white-eyed mail with a red-eyed female. What do you think all of the F1 offspring looked like? • Red-eyed • When he bred the F1 together he obtained what ratio? • 3:1 • But there was a slight difference from what Mendel’s theories would predict- the white trait was restricted to the males

10. Morgan’s conclusion • Morgan’s conclusion was that the gene for eye color is on the X chromosome • This means that the poor male flies get only a single copy, and if it is abnormal- they are abnormal • But the lucky ladies have two copies and are normal even if one copy is not.

11. Morgan’s conclusion • It is this male-female sex chromosomes difference that allows for sex-linked conditions. • If a gene for a recessive disease is present on the X-chromosome, then • a female must have two defective versions of the gene to show the disease • while a male only needs one  sorry boys

12. Morgan’s conclusions • Why? • This is because males have no corresponding gene on the Y chromosome to help counter the negative effect of a recessive allele on the X chromosome • Thus, more males than females show recessive X-linked phenotypes • In a pedigree, a pattern of sex-linked diseases will show the sons of a carrier mother with the disease

13. What role does the father play? • What do you think? • The father plays NO part in the passage of an X-linked gene to the male children of a couple • Fathers pass X-linked alleles to their daughters, but no to their sons • Do you understand why this is so? Can you explain it? • (The father does not give an X-chromosome to the male offspring because he is the one who provides the Y that makes his son a male. A mother can pass a sex-linked allele to both her daughters and sons because she can pass only X chromosomes to her offspring)

14. Common Sex linked disorders • Three common sex-linked disorders are Duchenne’s Muscular Dystrophy, hemophilia, and red-green color blindness • Duchenne’s muscular dystrophy • A sex linked disorder that is caused by the absesnce of an essential muscle protein • Its symptoms include progressive loss of muscle strength and coordination

15. Red-green color blindness • People afflicted are unable to distinguish between red and green colors • This condition is found primarily in males

16. Hemophilia • Hemophilia is caused by the absence of a protein vital to the clotting process. • Individuals with this condition have difficulty clotting blood after even the smallest of wounds • The most severely affected by this disease can bleed to death after the tiniest of injuries • Females with this condition rarely survive (why?)

17. X inactivation • Here’s an important question for you to think about… Are cells in a female identical? • The answer to this question is NO! Females undergo a process called X-inactivation. • During the development of female embryo, one of the two X chromosomes in each cell remains coiled as a Barr Body whose genes are not expressed

18. X inactivation • A cell expresses the alleles only of the active X chromosome • X inactivation occurs separately in each cell and involves random inactivation of one of a females X chromosomes • But not all cells inactivate the same X • As a result, different cells will have different active X chromosomes

19. X inactivation • Why don’t females always express X-linked diseases when this X inactivation occurs? • Sometimes they do, but usually they have enough cells with a “good” copy of the allele to compensate for the presence of the recessive allele

20. Holandric traits • The last sex related inheritance pattern is holandric traits, which are traits inherited via the Y chromosome • An example of a holandric trait in humans in ear hair distribution

21. Question time • Which of the following disorders is X-linked? • A. Tay-sachs disease • B. Cystic Fibrosis • C. Hemophilia • D. Albinism • E. Huntington Disease

22. Linkage and gene mapping

23. Linked genes • Each chromosome has hundreds of genes that tend to be inherited together because the chromosome is passed along as a unit • These are called linked genes • They lie on the same chromosome and do not follow Mendel’s law of independent assortment

24. Linked gene examples • Morgan performed an experiment in which he looked at the body color and wing size on his beloved fruit flies • The dominant alleles were G (gray) and V (normal wings); the recessive alleles were g (black) and v (vestigial wings). • GgVv females were crossed with ggvv males. What should the expected phenotypes be? • That’s not what Morgan found…

25. Linked genes results • Because the genes are linked, the gray/normal flies produce only GV or gv gametes • Thus, Morgan expected the ratio of offspring to be 1:1 half GgVv and half ggvv • What he found was that there were more wild type and double-mutant flies than independent assortment would predict • Surprisingly some Gv and gV were also produced

26. Crossing over • How did those other combinations result from the cross if the genes are linked? • Crossing over- a form of genetic combination that occurs during the prophase I of meiosis • The less often this recombination occurs, the closer genes must be on the chromosome. • The farther apart two genes are on a chromosome, the more often crossing over will occur. • Recombination frequency can be used to determine how close two genes are on a chromosome through the creation of linkage maps

27. Linkage maps • A linkage map is a genetic map put together using crossover frequencies • Another unit of measurement, the map unit (also known as centigram), is used to geographically relate the genes on the basis of these frequencies • One map unit = 1% crossover frequency • A linkage map does not provide the exact location of genes it gives only the relative position Less likely More likely

28. Linkage map practice • Try this problem: Imagine that you want to determine the relative locations of four genes: A, B, C, and D. • You know that A crosses over with C 20% of the time, B crosses over with C 15% of the time, A crosses over with D 10% of the time, and D crosses over with B 5% of the time. • Place these four genes in the correct order

29. Linkage map practice answer • From the information you can determine this sequence • Gene A must be 20 units from gene C • Gene B must be 15 units from C • But B could be 5 or 35 units from A • But because you also know that A is 10 units from D and D is 5 units from B, you can determine that B must be 5 units from A as well as if A is also to be 10 units from D • This gives you the sequence of genes as ABDC • A-----B-----D----------C

30. Journal • The following crossover frequencies were noted during experimentation for a set of five genes on a single chromosome: • A and B  35% • B and C  15% • A and C 20% • A and D  10% • D and B  25% • A and E  5% • B and E  40% • Create the linkage map for this example

31. Pedigrees • Pedigrees are family trees used to describe the genetic relationships within a family • Comprehension of the probability concept is important for a full understanding of pedigree analysis • What is the rule of multiplication? • What is the rule of addition?

32. Pedigree Key • Squares represent males • Circles are used for females • A horizontal line from male to female represents mates that have produced offspring • The offspring are listed below their parents from oldest to youngest • A fully shaded individual posses the trait being studied • If the condition being studied is a monogenic recessive condition (rr), then those shaded gray have the genotype rr • If the condition being studied is dominant condition (Rr or RR), then those that are unshaded have the genotype rr • A line through a symbol indicated that the person is deceased

33. Pedigree uses • Pedigree can be used in many ways • One use is to determine the risk of parents passing certain conditions to their offspring

34. Pedigree Practice Identify all of the carriers

35. Common disorders • There are many simple recessive disorders in which a person must be homozygous recessive for the gene in question to have the disease • The following diseases are commonly used as examples on the AP Bio exam and could also aid you in constructing a well-supported essay to answer a question about heredity and inhere tied disorders

36. Tay-sachs disease • A fatal genetic disorder that renders the body unable to break down a particular type of lipid that accumulates in the brain and eventually causes blindness and brain damage • Individuals typically do not survive more than a few years • Carriers of the disease do not show any of the effects of the disease and thus the allele is preserved in the population because carriers usually live to reproduce and potentially pass on the recessive copy of the allele. • This disease is found in a higher than normal percentage of people of eastern European Jewish descent

37. Tay-sachs disease

38. Cystic fibrosis (cf) • A recessive disorder • The most common fatal genetic disease in this country • The gene is located on chromosome 7 • The normal allele for the gene is involved in cellular chrloride ion transport • A defective version of the gene results in the excessive secretion of a thick mucus, which accumulates in the lungs and digestive tract. • Left untreated, children with CF die at a very young age • Statistically, one in 25 Caucasians is a carrier for this disease

39. Cystic fibrosis (CF)

40. Sickle cell anemia • A common recessive disorder that occurs as a result of an improper amino acid substitution during translation of an important red blood cell protein called hemoglobin • It results in the formation of a hemoglobin protein that is less efficient at carrying oxygen • It also causes hemoglobin to deform to a sickle shape when the oxygen content of the blood is low, causing pain, muscle weakness, and fatigue • It affects 1 out of every 400 African Americans and 1 out of every 10 African Americans is a carrier

41. Sickle cell anemia • The recessive trait is so prevalent because carriers (who are said to have the sickle cell “trait”) have increased resistance to malaria • In tropical regions, where malaria occurs, the sickle trait actually increases an individuals probability of survival, and thus the traits presence in the population increases (heterozygote advantage)

42. Sickle cell anemia

43. Phenylketonuria (PKU) • Autosomal recessive disease caused by a single gene defect • Children with PKU are unable to successfully digest phenylalanine (an amino acid). • This leads to the accumulation of a by-product in the blood that can cause mental retardation • If the disease is caught early, retardation can be prevented by avoiding phenylalanine in the diet

44. Huntington disease • Autosomal dominant (less common) • A fatal disease that causes the breakdown of the nervous system • Does not show itself until a person is in their 30s or 40s and individuals afflicted with this condition have a 50% chance of passing it to their offspring

45. Huntington disease

46. Lethal dominant vs lethal recessive • Why are lethal dominant alleles less common than lethal recessive alleles? • Think about how recessive alleles often are passed on from generation to generation. • An individual can be a carrier of a recessive condition and pass it along without even knowing it. • On the other hand, it is impossible to be an unaffected carrier of a dominant condition, and many lethal conditions have unfortunately killed the individual before reproductive maturity has been achieved • This makes it more difficult for the dominant gene to be passed along • To remain prevalent in the population, a dominant disorder must not kill the individual until reproduction has occured

47. Question Time Use the pedigree of an autosomal recessive condition to answer the questions • 1. What is the genotype of person A? • A. Bb B. BB C. bb D. Cant be determined • 2. What is the most likely genotype of person B? • A. Bb B. BB C. bb D. Cant be determined • 3. What is the probability that persons C and D would have a child with the condition? • A. ½ B. ¼ C. 1/6 D. 1/8 E. 1/10 A D C B

48. Journal(Draw and answer) • This pedigree most likely a pedigree of a condition of which type of inheritance? • A. autosomal dominant • B. Autosomal recessive • C. Sex-linked dominant • D. Sex-linked recessive • E. A gene present only on the Y chromosome (holandric)

49. Chromosomal Complications

50. Chromosomal complications • We have spent a lot of time talking about how genes are inherited and passed from generation to generation • It is also important to discuss the situations in which something goes wrong with the chromosomes themselves that affects the inheritance of genes by the offspring.