1. Chromosomal Inheritance Chapter 12

2. Drosophila Chromosomes

3. 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 smallest (#1) to largest (#22)  The sex chromosomes are numbered as the 23rd pair  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 smallest (#1) to largest (#22)  The sex chromosomes are numbered as the 23rd pair

4. 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 chromosomes 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.  Therefore, the sex of all humans is determined by the sperm donated by their father.  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 chromosomes 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.  Therefore, the sex of all humans is determined by the sperm donated by their father.

5. X-linked Alleles  Genes carried on autosomes are said to be autosomally linked  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  Genes carried on autosomes are said to be autosomally linked  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

6. 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 genotypes and phenotypes  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 genotypes and phenotypes GenotypePhenotype XRXRXRXR Homozygous DominantFemaleRed-eyed XRXrXRXr HeterozygousFemaleRed-eyed XrXrXrXr Homozygous RecessiveFemaleWhite-eyed XRYXRYMonozygous DominantMaleRed-eyed XrYXrYMonozygous RecessiveMaleWhite-eyed

7. X-linked Inheritance

8. 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 gene for blue-sensitive is autosomal  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 (X b Y) are colorblind  Only homozygous mutant females (X b X b ) are colorblind  Heterozygous females (X B X b ) are asymptomatic carriers  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 gene for blue-sensitive is autosomal  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 (X b Y) are colorblind  Only homozygous mutant females (X b X b ) are colorblind  Heterozygous females (X B X b ) are asymptomatic carriers

9. Red-Green Colorblindness Chart

10. X-linked Recessive Pedigree

11. 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 are male  Defective gene always unopposed in males  Males die before fathering potentially homozygous recessive daughters  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 are male  Defective gene always unopposed in males  Males die before fathering potentially homozygous recessive daughters

12. 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 X  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.  Factor VIII now available via biotechnology  “Bleeder’s Disease”  Blood of affected person either refuses to clot or clots too slowly  Hemophilia A -due to lack of clotting factor X  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.  Factor VIII now available via biotechnology

13. Hemophilia Pedigree

14. 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  Inheritance pattern is complex and unpredictable  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  Inheritance pattern is complex and unpredictable

15. Gene Linkage

16.  When several genes of interest exist on the same chromosome  Such genes form a linkage group  Tend to be inherited 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  When several genes of interest exist on the same chromosome  Such genes form a linkage group  Tend to be inherited 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

17. Linkage Groups

18. 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  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  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  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

19. Crossing-Over

20. Complete vs. Incomplete Linkage

21. 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 in tetraploid species that is self-fertile but isolated from both “parent” species  Ofen lethal in higher animals  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 in tetraploid species that is self-fertile but isolated from both “parent” species  Ofen lethal in higher animals

22. Chromosome Number: Aneuploidy  Monosomy (2n-1)  Diploid individual has only one of a particular chromosome  Caused by failure of synapsed chromosome to separate at Anaphase (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 nonsomic daughter cell and one trisomic daughter cell in meiosis I  Down syndrome is trisomy 21  Monosomy (2n-1)  Diploid individual has only one of a particular chromosome  Caused by failure of synapsed chromosome to separate at Anaphase (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 nonsomic daughter cell and one trisomic daughter cell in meiosis I  Down syndrome is trisomy 21

23. Nondisjunction

24. Trisomy 21

25. Chromosome Number: Abnormal Sex Chromosome Number  Result of inheriting too many or too few X or Y chromosomes  Caused by nondisjunction during oogenesis or spermatogenesis  Turner Syndrome (XO)  Female with single X chromosome  Short, with broad chest and widely spaced nipples  Cam be of normal intelligence and function with hormone therapy  Result of inheriting too many or too few X or Y chromosomes  Caused by nondisjunction during oogenesis or spermatogenesis  Turner Syndrome (XO)  Female with single X chromosome  Short, with broad chest and widely spaced nipples  Cam be of normal intelligence and function with hormone therapy

26. Chromosome Number: Abnormal Sex Chromosome Number  Klinefelter Syndrome (XXY)  Male with underdeveloped testes and prostate; some breast overdevelopment  Long arms and legs; large hands  Near normal intelligence unless XXXY, XXXXY, etc.  No matter how many X chromosomes, presence of Y renders individual male  Klinefelter Syndrome (XXY)  Male with underdeveloped testes and prostate; some breast overdevelopment  Long arms and legs; large hands  Near normal intelligence unless XXXY, XXXXY, etc.  No matter how many X chromosomes, presence of Y renders individual male

27. Turner & Klinefelter Syndromes

28. Chromosome Number: Abnormal Sex Chromosome Number  Ploy-X females  XXX simply taller and thinner than normal  Some learning difficulties  Many menstruate regularly and are fertile  More than 3 Xs renders severe mental retardation  Jacob’s syndrome (XYY)  Tall, persistent acne, speech and reading problems  Ploy-X females  XXX simply taller and thinner than normal  Some learning difficulties  Many menstruate regularly and are fertile  More than 3 Xs renders severe mental retardation  Jacob’s syndrome (XYY)  Tall, persistent acne, speech and reading problems

29. Abnormal Chromosome Structure  Deletion  Missing segment of chromosme  Lost during breakage  Translocation  A segment from one chromosome moves to a non-homologous chromosome  Follows breakage of two homologous chromosomes and improper re-assembly  Deletion  Missing segment of chromosme  Lost during breakage  Translocation  A segment from one chromosome moves to a non-homologous chromosome  Follows breakage of two homologous chromosomes and improper re-assembly

30. Deletion, Translocation, Duplication, & Inversion

31. Abnormal Chromosome Structure  Duplication  A segment of a chromosome is repeated in the same chromosome  Inversion  Occurs as a result of two breaks in a chromosome  The internal segment is reversed before reinsertion  Genes occur in reverse order in inverted segment  Duplication  A segment of a chromosome is repeated in the same chromosome  Inversion  Occurs as a result of two breaks in a chromosome  The internal segment is reversed before reinsertion  Genes occur in reverse order in inverted segment

32. Inversion Leading to Duplication & Deletion

33. Abnormal Chromosome Structure  Deletion Syndromes  Williams Syndrome -- loss of segment of chromosome 7  Cri du chat syndrome (cat’s cry) -- loss of segment of chromosome 5  Translocation  Alagille syndrome  Some cancers  Deletion Syndromes  Williams Syndrome -- loss of segment of chromosome 7  Cri du chat syndrome (cat’s cry) -- loss of segment of chromosome 5  Translocation  Alagille syndrome  Some cancers

34. Williams Syndrome

35. Alagille Syndrome