HUMAN REPRODUCTION BIOLOGY 269

1. HUMAN REPRODUCTIONBIOLOGY 269

2. Humans: • Reproduce sexually with internal fertilization • The purpose of sex, of course, is to get an egg fertilized by a sperm, combining the chromosomes that each contains. This occurs a few hours after both: a. b. It occurs within the Fallopian tube, about one third of the way from the ovary to the uterus

3. The basis of genetic inheritance: of chromosomes (46 total) All cells in the body except sperm and eggs (and the cells which are forming these) have all 46. Sperm and eggs have only 22 of these pairs = 23rd pair =

4. The basis of genetic inheritance: • Each chromosome consists of a very long molecule called Genes are short segments of this DNA, lined up one after the other

5. Each of your eggs or sperm contains 23 chromosomes • so • During their formation (“oogenesis” or “spermatogenesis”) each receives only half of the original 46 chromosomes More specifically: This is a mixture of chromosomes you got from your mother and chromosomes you got from your father

6. This is different than the type of cell division, called in which cells simply make genetically identical copies of themselves • This reduction in the number of chromosomes, from 46 to 23 in sperm or eggs, requires a specific type of cell division called

7. Key features: • Mitosis: One cell copies its chromosomes and then divides in such a way that each of the two new cells is genetically identical to the original: each contains all 23 pairs = 46 chromosomes Meiosis: One cell copies its chromosomes and then divides twice in succession so that four new cells are formed, each of which contains 23 single chromosomes (no pairs) You’re in luck! For this course, you don’t need to know any more detail than that about mitosis vs meiosis: Mitosis: Meiosis:

8. While both sperm and eggs are formed by meiosis, the processes are not identical: Spermatogenesis forms Very rapid - hundreds of millions of sperm produced each day. Oogenesisforms Much slower - one or two eggs (oocytes) produced each month.

9. Recall: • Fertilization combines sperm (23 chromosomes) and egg (23 chromosomes) to form a zygote (46 chromosomes). This zygote divides repeatedly by mitosis to form the billions of cells which make up the different organs of the body, each of which contains these same 46 chromosomes.

10. While all cells (except sperm and eggs) CONTAIN all of the chromosomes and thus all of the genes • Not all of the cells EXPRESS all of their genes • That is: only some of the genes will be expressed in any particular cell. e.g. skin, hair, and eye cells express genes for color, but liver cells or heart cells do not; cells in your pancreas express the genes to produced insulin, other types of cells do not.

11. Also recall: • Your chromosomes are arranged in pairs (one from each parent), so you have two genes for each “trait”

12. Two genes for the same trait, carried on different chromosomes of a pair, are called • These alleles may be the same (e.g. both are for brown hair) or different (one for brown hair, one for blond hair) You are considered for a trait if both alleles are the same, or if the two alleles are different

13. Sometimes one allele will always • be expressed if it is present • Sometimes an allele will be expressed • only if a dominant allele not present • Sometimes the two different alleles • will both be completely expressed • Sometimes one allele will only be • partially expressed if a recessive • allele is also present

14. What alleles you carry (regardless of which ones are actually expressed) is your • What traits you actually express (regardless of which alleles are actually present) is your

15. Example: • Allele (gene) for hairy ears is dominant “H” • Allele (gene) for hairless ears is recessive “h” • (remember: you have two alleles for this trait: one from your mother and one from your father) If genotype is HH (homozygous), phenotype is hairy ears If genotype is Hh (heterozygous), phenotype is hairy ears If genotype is hh (homozygous), phenotype is hairless ears

16. Example: • Allele (gene) for type A blood is dominant “A” • Allele (gene) for type B blood also dominant “B” • Allele (gene) for type O blood is recessive “o” • (remember: you have only two alleles for this trait: one from your mother and one from your father) If genotype is AA (homozygous), phenotype is type A blood If genotype is Ao (heterozygous), phenotype is type A blood If genotype is BB (homozygous), phenotype is type B blood If genotype is Bo (heterozygous), phenotype is type B blood If genotype is AB (heterozygous), phenotype is type AB blood If genotype is oo (homozygous), phenotype is type O blood

17. Example: • Allele (gene) for producing hormone insulin is dominant “I” • Allele (gene) for not producing insulin is recessive “i” • (remember: you have two alleles for this trait: one from your mother and one from your father) If genotype is II (homozygous), phenotype is producing insulin If genotype is Ii (heterozygous), phenotype is producing insulin If genotype is ii (homozygous), phenotype is no insulin produced

18. If you know the genotypes of both parents, you can calculate the probability of a child having a particular genotype and/or a particular phenotype. A handy tool for doing this is a Punnett square, in which each allele in the sperm or egg is listed, along with all possible combinations upon fertilization Allele Allele Combined Alleles Combined Alleles Allele Combined Alleles Combined Alleles Allele

19. Example: Allele (gene) for hairy ears is dominant “H”Allele (gene) for hairless ears is recessive “h” • Suppose a homozygous recessive man and a heterozygous woman have children. What are the probabilities of the resulting genotypes and phenotypes?

20. Change things a bit: Allele (gene) for hairy ears is dominant “H”Allele (gene) for hairless ears is recessive “h” • Suppose both parents are heterozygous. What are the probabilities of the resulting genotypes and phenotypes?

21. Example: Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o” • Suppose the father is homozygous for type A blood and the mother is heterozygous for type B blood. What are the probabilities of the resulting genotypes and phenotypes?

22. Change the parents’ blood types: Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o” • Suppose the father is heterozygous for type A blood and the mother is heterozygous for type B blood. What are the probabilities of the resulting genotypes and phenotypes?

23. Let’s try it from a different perspective: Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o” • Could a father who has type A blood (you don’t know if he is homozygous or heterozygous) and a mother who has type AB blood have a child with type O blood?

24. Here’s another one: Allele (gene) for brown eyes is dominant to other colors “B”Allele (gene) for green eyes is dominant over blue “g”Allele (gene) for blue eyes is recessive to all other colors “b” • Suppose the father is heterozygous with alleles for brown eyes and for green eyes, and the mother is heterozygous with alleles for green eyes and blue eyes. What are the probabilities of the resulting genotypes and phenotypes?

25. Example: The allele (gene) for straight hair “S” is incompletely dominant over the allele for curly hair “s”; the heterozygous genotype produces an intermediate form, wavy hair. • Suppose the father is heterozygous, and the mother is homozygous for curly hair. What are the probabilities of the resulting genotypes and phenotypes?

26. Let’s change the parents genetics: The allele (gene) for straight hair “S” is incompletely dominant over the allele for curly hair “s”; the heterozygous genotype produces an intermediate form, wavy hair. • Suppose the both parents are heterozygous. What are the probabilities of the resulting genotypes and phenotypes?

27. Disclaimer:Genetics is not really as simple as I have presented: Many alleles considered “dominant” are really incompletely dominant, with the recessive allele being only slightly expressed (e.g. individuals who are homozygous for brown eyes have darker brown eyes than individuals who are heterozygous) Many traits are controlled by more than one pair of alleles, with many different genes determining the final phenotype (e.g. skin color varies from very light to very dark, depending on how many pairs of alleles contain one for producing the pigment melanin)

28. Disclaimer:Genetics is not really as simple as I have presented: The expression of an otherwise dominant allele can be blocked by a different pair of alleles (e.g. an individual with an allele for brown eyes may not express it if another gene turns off its expression, thus having green or blue eyes). This can vary among different cells in the same tissue (e.g. many individuals have regions of different colors in the same eye)

29. Many genes (alleles) produce physical / physiological abnormalities or disease • All of the genetic “rules” just discussed can apply to these as well: • - Dominance and recessiveness • - Codominance and incomplete dominance • - Multiple pairs of alleles • - Blockage • - Different expression in different cells

30. Example: The allele which produces the disease neurofibromatosis (“N”) is dominant to the normal allele (“n”) • What is the probability of a child getting this disease if one parent is normal but the other carries an allele for the disease?

31. Neurofibromatosis: Autosomal dominant

32. Change the parents’ genetics: The allele which produces the disease neurofibromatosis (“N”) is dominant to the normal allele (“n”) • What if both parents are heterozygous for the disease-producing allele?

33. Example: The allele which produces the disease achondroplasia (“a”) is recessive to the normal allele (“A”) • What is the probability of a child getting this disease if one parent is normal but the other carries one allele for the disease?

34. Change the parents’ genetics: The allele which produces the disease achondroplasia (“a”) is recessive to the normal allele (“A”) • What if both parents are heterozygous for the disease-producing allele?

35. “Special case” when an allele is located on the X-chromosome Women (genotype = XX) will have two alleles for that trait, just as we have been discussing Men (genotype = XY) will have only one allele for that trait since they have only one X-chromosome, and that allele will always be expressed (the Y chromosome carries completely different alleles than the X chromosome) If that allele is disease-producing:

36. Example: Duchenne muscular dystrophy is produced by an X-linked recessive allele “Xd” • Suppose the father is normal (XDY) but the mother is heterozygous for the disease (XD Xd)

37. Chromosomes are formed by long strands of a molecule called deoxyribonucleic acid, or DNA. This molecule can best be thought of by analogy to the written English language, in which letters make up words, which make up sentences, which make up paragraphs. In DNA: There are four possible “letters”, which we will call ; All “words” are exactly three letters long; “Sentences” are typically thousands of words long. Each “sentence” would be one gene; The entire “paragraph” would be one chromosome

38. Let’s rephrase that: • Chromosomes are formed by very long molecules called DNA, which consist of genes lined up one-after-the-other. • Each of these genes consists of many three-letter groupings of A, C, G, and T, lined up one-after-the-other For example, a very short gene might consist of A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C-G-T-C

39. Things often go wrong during mitosis or meiosis: • Recall: • Chromosomes are formed by very long molecules called DNA, which consist of genes lined up one-after-the-other. • Each of these genes consists of many three-letter groupings of A, C, G, and T, lined up one-after-the-other • So that a very short gene might consist of • A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C-G-T-C

40. Minor changes, or mutations, may occur in a gene • 1) A piece of it may be deleted, for example • If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C • becomes A-C-T-G-A-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C • (three letters deleted) • Or A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C • becomes A-C-T-G-A-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C • (one letter deleted)

41. (Minor changes, or mutations, may occur in a gene) • 2) A piece of it may be added, for example • If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A • becomes A-C-T-G-A-C-T-G-C-G-A-C-T-G-C T-T-A-A-C-C-T-C-A • (. . six letters added. .) • One or more of the “letters” may substituted, for example • If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C becomes A-C-T-G-T-C-T-G-C-T-G-A-A-C-C-C-C-A-G-A-C-C-C-T

42. While seemingly minor at the letter level, mutations will in fact have very serious effects on the ability of that gene to produce its normal trait, just as it would in the English language: For example • If: The old cat and the big dog ate all the ham • became The olc ata ndt heb igd oga tea llt heh am (deletion) If: The old cat and the big dog ate all the ham became The odd cat and the big log ate all the hat (substitution)

43. Just as with the language examples given, the vast majority of mutations cause the gene to become “nonsense”: the trait is no longer produced. Many cases: expression of the trait is necessary for life, so mutation kills whatever cell it occurs in. Far fewer cases: Cell will still be able to survive, but will be missing something – for example, if the cell normally produced the brown pigment melanin and this gene mutates, the cell could still be alive but will no longer be brown. Extremely few circumstances (once out of many millions of mutations): absence of a trait improves the function of the cell – for example, if it could now produce even more energy than it did before.

44. Another genetic change which occurs during mitosis or meiosis is, in which normal chromosomes may get distributed abnormally into the daughter cells

45. As with mutations, the vast majority of cells in which nondisjunction occurs will die, but a few may live and develop abnormal functions.

46. If a cell dies during mitosis or meiosis, it usually has very little effect on the organ which contains that cell, since it can easily be replaced by mitosis of another, healthy cell. However, if a genetically abnormal cell survives from mitosis, it can have a serious effect because of its abnormal function: • It may produce something which is toxic to other cells; • It may produce things which make other cells function abnormally; • It may lose its ability to regulate its growth and division = Cancer;

47. If a genetically abnormal cell (sperm or egg) survives meiosis and is then involved in fertilization, the changes can be passed on to the children In most cases, genetically abnormal embryos die before birth. In a few cases, however, they survive. In fact the vast majority of birth defects are caused by genetic abnormalities.

48. Down syndrome: Trisomy 21

49. One of the more common birth defects involves nondisjunction of the X and Y sex chromosomes • Recall: Each egg normally carries one X chromosome and no Y • Each sperm normally carries either one X chromosome or • one Y chromosome • Therefore, cells in a normal zygote and embryo will have either two X chromosomes or one X and one Y chromosome X Y X X XX XX XY XY

50. As a result of nondisjunction, a sperm or egg may either - Be missing the sex chromosome, or - Have an extra sex chromosome • If this sperm or egg is involved in fertilization, the zygote and all subsequent cells will either • - Be missing one sex chromosome, or • - Have an extra sex chromosome