Ch.12 Chromosomal Basis of Inheritance

1. Ch.12 Chromosomal Basis of Inheritance

2. Essential knowledge 3.A.3 • The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring. • a. Rules of probability can be applied to analyze passage of single gene traits from parent to offspring. • b. Segregation and independent assortment of chromosomes result in genetic variation. • c. Certain human genetic disorders can be attributed to the inheritance of single gene traits or specific chromosomal changes, such as nondisjunction. • d. Many ethical, social and medical issues surround human genetic disorders.

3. Essential knowledge 3.B.2: • A variety of intercellular and intracellular signal transmissions mediate gene expression. • a. Signal transmission within and between cells mediates gene expression. • b. Signal transmission within and between cells mediates cell function.

4. Essential knowledge 3.A.1: • DNA, and in some cases RNA, is the primary source of heritable information. • a. Genetic information is transmitted from one generation to the next through DNA or RNA. • b. DNA and RNA molecules have structural similarities and differences that define function. • c. Genetic information flows from a sequence of nucleotides in a gene to a sequence of amino acids in a protein. • d. Phenotypes are determined through protein activities. • e. Genetic engineering techniques can manipulate the heritable information of DNA and, in special cases, RNA.

5. Essential knowledge 3.C.1: • Changes in genotype can result in changes in phenotype. • a. Alterations in a DNA sequence can lead to changes in the type or amount of the protein produced and the consequent phenotype. • b. Errors in DNA replication or DNA repair mechanisms, and external factors, including radiation and reactive chemicals, can cause random changes, e.g., mutations in the DNA. • c. Errors in mitosis or meiosis can result in changes in phenotype. • d. Changes in genotype may affect phenotypes that are subject to natural selection. Genetic changes that enhance survival and reproduction can be selected by environmental conditions.

6. Mendelian inheritance has its physical basis in the behavior of chromosomes • The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

7. The chromosome theory of inheritance states that • Mendelian genes have specific loci on chromosomes

8. Chromosomal Inheritance • Humans are diploid (2 chromosomes of each type) • Humans have 23 different kinds of chromosomes • Arranged in 23 pairs of homologous chromosomes • Total of 46 chromosomes (23 pairs) per cell • One of the chromosome pairs determines the sex of an individual (The sex chromosomes) • The other 22 pairs of chromosomes are autosomes • Autosomal chromosomes are numbered from largest (#1) to smallest (#22)

9. The Chromosomal Basis of Sex • An organism’s sex • Is an inherited phenotypic character determined by the presence or absence of certain chromosomes

10. Sex Determination in Humans • Sex is determined in humans by allocation of chromosomes at fertilization • Both sperm and egg carry one of each of the 22 autosomes • The egg always carries the X chromosome as number 23 • The sperm may carry either and X or Y • If the sperm donates an X in fertilization, the zygote will be female • If the sperm donates a Y in fertilization, the zygote will be male

11. In humans and other mammals • There are two varieties of sex chromosomes, X and Y

12. Different systems of sex determination • Are found in other organisms

13. Inheritance of Sex-Linked Genes • A gene located on either sex chromosome is called a sex-linked gene • Sex chromosomes also have genes for many characters unrelated to maleness and femaleness, these genes are usually found on the X-chromosome, since males and females have at least one X chromosome

14. Sex-linked genes • Follow specific patterns of inheritance

15. Sex-linked recessive disorders affect mostly males, because males need to inherit only one recessive allele to show the trait, while females need to inherit two recessive alleles

16. Male consequently have only one copy of these genes XRY or XrY, so they express what ever single allele they possess • Females have two X chromosomes and can be: XRXR or XRXr or XrXr they would need two recessive alleles to show the recessive phenotype

17. X-Linked Alleles • Genes carried on the female sex chromosome (X) are said to be X-linked (or sex-linked) • X-linked genes have a different pattern of inheritance than autosomal genes have • The Y chromosome is blank for these genes • Recessive alleles on X chromosome: • Follow familiar dominant/recessive rules in females (XX) • Are always expressed in males (XY), whether dominant or recessive • Males said to be monozygous for X-linked genes

18. Sex linked recessive disorders • Some recessive alleles found on the X chromosome in humans cause certain types of disorders • Color blindness • Duchenne muscular dystrophy • Hemophilia

19. Eye Color in Fruit Flies • Fruit flies (Drosophila melanogaster) are common subjects for genetics research • They normally (wild-type) have red eyes • A mutant recessive allele of a gene on the X chromosome can cause white eyes • Possible combinations of genotype and phenotype:

20. Human X-Linked Disorders: Muscular Dystrophy • Muscle cells operate by release and rapid sequestering of calcium • Protein dystrophin required to keep calcium sequestered • Dystrophin production depends on X-linked gene • A defective allele (when unopposed) causes absence of dystrophin • Allows calcium to leak into muscle cells • Causes muscular dystrophy • All sufferers male • Defective gene always unopposed in males

21. Human X-Linked Disorders: Hemophilia • “Bleeder’s Disease” • Blood of affected person either refuses to clot or clots too slowly • Hemophilia A – due to lack of clotting factor IX • Hemophilia B – due to lack of clotting factor VIII • Most victims male, receiving the defective allele from carrier mother • Bleed to death from simple bruises, etc.

22. Analyzing pedigrees • Is recessive trait autosomal or sex-linked? • Sex-linked traits occur more often in males (almost always); if a female has the trait, the father will show and mother must show or be a carrier

23. Human X-Linked Disorders: Red-Green Color Blindness • Color vision In humans: • Depends three different classes of cone cells in the retina • Only one type of pigment is present in each class of cone cell • The red-sensitive and green-sensitive genes are on the X chromosome • Mutations in X-linked genes cause RG color blindness: • All males with mutation (XbY) are colorblind • Only homozygous mutant females (XbXb) are colorblind • Heterozygous females (XBXb) are asymptomatic carriers

24. Human X-Linked Disorders: Fragile X Syndrome • Due to base-triplet repeats in a gene on the X chromosome • CGG repeated many times • 6-50 repeats – asymptomatic • 230-2,000 repeats – growth distortions and mental retardation

25. One gene on the Y chromosome (SRY gene) triggers testes development – the lack of this gene causes development of ovaries instead of testes • Y chromosome contains a gene that produces a protein which binds to the DNA of an autosome and turns on genes that produce male characteristics

26. X inactivation in Female Mammals • In mammalian females • One of the two X chromosomes in each cell is randomly inactivated during embryonic development to become a barr body

27. If a female is heterozygous for a particular gene located on the X chromosome • She will be a mosaic for that character

28. Sex-Influenced Traits • Some traits such as growth and development of penis, vagina, uterus, oviducts, body hair, breast size, voice pitch are controlled by autosomes. • The sex chromosome determines which hormone is produced, and ultimately affects how the secondary sex characteristics are developed

29. Linked Genes • Linked genes tend to be inherited together because they are located near each other on the same chromosome

30. Gene Linkage • Such genes form a linkage group • Tend to be inherited as a block • If all genes on same chromosome: • Gametes of parent likely to have exact allele combination as gamete of either grandparent • Independent assortment does not apply • If all genes on separate chromosomes: • Allele combinations of grandparent gametes will be shuffled in parental gametes • Independent assortment working

31. P-purple, p-red; L-long, l-round • If P/L and p/l are not linked, they assort independently to produce gametes: PL, Pl, pL, pl • The dihybrid cross: PpLl x PpLl produces offspring occurring in a 9:3:3:1 ratio 9 purple,long: 3 purple,round: 3 red,long: 1red,round • If PL and pl are linked, they do not assort independently and produce only the gametes: PL, pl • The dihybrid cross: PL/pl x PL/pl produces offspring occurring in a 3:1 ratio 3 purple,long: 1red,round

32. How Linkage Affects Inheritance: Scientific Inquiry • Morgan did other experiments with fruit flies • To see how linkage affects the inheritance of two different characters

33. Morgan determined that • Genes that are close together on the same chromosome are linked and do not assort independently • Unlinked genes are either on separate chromosomes or are far apart on the same chromosome and assort independently

34. When Mendel followed the inheritance of two characters • He observed that some offspring have combinations of traits that do not match either parent in the P generation

35. If YR and yr were linked, a cross between parents that were YyRr x yyrr would produce only YyRr (yellow, round) and yyrr (green, wrinkled)

36. Recombinant offspring • Are those that show new combinations of the parental traits • When 50% of all offspring are recombinants

37. Recombination of Linked Genes: Crossing Over • Morgan discovered that genes can be linked • But due to the appearance of recombinant phenotypes, the linkage appeared incomplete

38. Morgan proposed that • Some process must occasionally break the physical connection between genes on the same chromosome

39. Linked genes • Exhibit recombination frequencies less than 50%

40. Ratio for Unlinked Expected Ratio for linked Expected Actual These phenotypes/genotypes (25, 25) must have occurred as a result of crossing over

41. The recombination frequency is equal to: # of recombinants resulting from crossing over total # of offspring recombination = 50 = .13 or 13% frequency 400 This is sometimes expressed as map units

42. Genes farther apart would have a higher frequency of crossing over and would be more map units apart • Those closely linked would have smaller chance of crossing over-this would translate to less map units

43. Linkage Mapping: Using Recombination Data: Scientific Inquiry • A genetic map • Is an ordered list of the genetic loci along a particular chromosome

44. A linkage map • Is the actual map of a chromosome based on recombination frequencies

45. The farther apart genes are on a chromosome • The more likely they are to be separated during crossing over

46. Many fruit fly genes • Were mapped initially using recombination frequencies

47. Constructing a Chromosome Map • Crossing-over can disrupt a blocked allele pattern on a chromosome • Affected by distance between genetic loci • Consider three genes on one chromosome: • If one at one end, a second at the other and the third in the middle • Crossing over very likely to occur between loci • Allelic patterns of grandparents will likely to be disrupted in parental gametes with all allelic combinations possible • If the three genetic loci occur in close sequence on the chromosome • Crossing over very UNlikely to occur between loci • Allelic patterns of grandparents will likely to be preserved in parental gametes • Rate at which allelic patterns are disrupted by crossing over: • Indicates distance between loci • Can be used to develop linkage map or genetic map of chromosome

48. Chromosome Number: Polyploidy • Polyploidy • Occurs when eukaryotes have more than 2n chromosomes • Named according to number of complete sets of chromosomes • Major method of speciation in plants • Diploid egg of one species joins with diploid pollen of another species • Result is new tetraploid species that is self-fertile but isolated from both “parent” species • Often lethal in higher animals

49. Chromosome Number: Aneuploidy • Monosomy (2n - 1) • Diploid individual has only one of a particular chromosome • Caused by failure of synapsed chromosomes to separate at Anaphase I (nondisjunction) • Trisomy (2n + 1) occurs when an individual has three of a particular type of chromosome • Diploid individual has three of a particular chromosome • Also caused by nondisjunction • This usually produces one monosomic daughter cell and one trisomic daughter cell in meiosis I

50. Changes in chromosome number can result from accidents like non-disjunction • Non-disjunction occurs when members of a chromosome pair fail to separate • Also can occur during meiosis II when chromatids fail to separate • Results in cells (gametes) having too few or too many chromosomes