1. Ch. 12 Outline – Chromosomal Inheritance
X-Linked Alleles
Human X-Linked Disorders
Gene Linkage
Crossing-Over
Chromosome Map
Changes in Chromosome Number
Changes in Chromosome Structure
Human Syndromes

2. 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

3. 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
Therefore, the sex of all humans is determined by the sperm donated by their father

4. Genes carried on autosomes are said to be autosomally linked
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

5. 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:
Genotype
Phenotype
XRXR
Homozygous Dominant
Female
Red-eyed
XRXr
Heterozygous
XrXr
Homozygous Recessive
White-eyed
XRY
Monozygous Dominant
Male
XrY
Monozygous Recessive

6. Drosophila Chromosomes

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 (XbY) are colorblind
Only homozygous mutant females (XbXb) are colorblind
Heterozygous females (XBXb) 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 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 VIII
Hemophilia B – due to lack of clotting factor IX 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

15. Gene Linkage

16. When several genes of interest exist on the same chromosome
Gene Linkage
When several genes of interest exist on the same chromosome
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

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
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

19. Crossing Over

20. Complete vs. Incomplete Linkage

21. Chromosome Number: 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
Some estimate 47% of flowering plants are polyploids
Often 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 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
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
Can 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

27. Turner and Klinefelter Syndromes

28. Chromosome Number: Abnormal Sex Chromosome Number
Ploy-X females
XXX simply taller & thinner than usual
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 & reading problems

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

30. Deletion, Translocation, Duplication, and 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 re-insertion
Genes occur in reverse order in inverted segment

32. Inversion Leading to Duplication and 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
Translocations
Alagille syndrome
Some cancers

34. Williams Syndrome

35. Alagille Syndrome