1. Chromosomal Arrangement

2. Variations in Chromosome Number and Arrangement
Chromosomal mutations or aberrations
Abnormal chromosomal number
Gene deletion or duplication
Chromosome rearrangements
Aberrant (different from the norm) chromosomes are passed on in a Mendelian fashion (Independent assortment during Meiosis)

3. Terminology
Euploid (Eu=True) – chromosomes present in complete haploid units
Diploid
Triploid
Tetraploid
Aneuploid – loss or gain of one or more chromosomes (2n+x, 2n-x)
Alloploid – multiples of different genomes

5. Aneuploidy Commonly results from nondisjunction during meiosis
Monosomy 2n-1
Trisomy 2n+1
Tetrasomy 2n+2, Pentasomy 2n+3…..
Klinefelter (XXY) and Turner syndromes (X) are examples of Aneuploidy involving human sex chromosomes

6. Kleinfelter Syndrome Anatomical Characteristics

7. Turner Syndrome Characteristics

8. Nondisjunction

10. Aneuploidy - Monosomy 2n – 1 condition
Monosomy involving autosomes may have severe phenotypic effects in animal species (but generally not plants)
Monosomy for Drosophila chromosome 4 (only 5% of genome) gives live fly but small and with low viability
Monosomy for chromosomes 2 and 3 lethal

11. Cri-du-Chat Syndrome
Autosomal monosomy in humans not usually reported beyond birth (die quickly)
Partial autosomal monosomy may survive
Segmental deletions of chromosomes
“Cry of cat” syndrome
Loss of part of 5p arm (46, -5p)
1/50,000 births

12. Cri-du-Chat

13. Aneuploidy - Trisomy Trisomy (2n + 1) Meiotic issues
Somewhat/slightly less severe than monosomy when involves autosome
Large autosomes usually lethal in both Drosophila and humans
Generally viable in plants
Meiotic issues
Anaphase has one going to one cell, two to the other

14. Trisomy Meiosis

15. Down Syndrome (Trisomy 21)
Discovered in 1866 by John Langdon Down
Now known to result from trisomy 21 (47 +21)
Occurs at 21st position in karyotype
Occurs one per 800 live births
75% due to nondisjunction in meiosis I
Ovum is source of extra 21 in 95% of cases
Maternal age
Ova can be stalled in meiosis I for 20 or more years…
Familial Down syndrome is the result of a translocation of a portion of chromosome 21

17. Down Syndrome – Trisomy 21

18. Maternal Age and Down Syndrome
1/1000 births when maternal age is 30
1/100 at age 40
1/50 at age 50

19. Aneuploidy - Patau Syndrome
Trisomy 13 (47 +13)
occurs at 13th position in karyotype
1/19,000 births
Many problems; death commonly by 3 months
Some parental age correlation but average age of parent is somewhat higher than for normal children
No evidence yet for maternal or paternal probabilities as source of extra chromosome

20. Patau Syndrome

21. Warning, the next slide is graphic

22.                                                                                                                                                 
A 37 2/7 week gestational age male infant with Patau syndrome demonstrating alobar holoprosencephaly with cyclopia. A) Facial features included sloping forehead with a proboscis superior to a single central palpebral fissure. B) Close-up of the fused eyelids and proboscis showing a single nostril. C) Polydactyly showing six digits. D) Posterior view of the brain showing indistinct gyri, fusion of the hemispheres, and occipital encephalocele.E) Transposition of the aorta (A), and hypoplastic pulmonary trunk (P). F) Trisomy 13 [47, XY, +13] (karyotype by Giemsa-banding).
Chan et al. Diagnostic Pathology :48   doi: /

23. Aneuploidy - Edwards Syndrome
Trisomy 18 (47 +18)
Occurs at 18th position in karyotype
Many problems, survival less than 4 months
Occurs 1/8000 live births
80% female (in study of 143 cases)
Average maternal age is high (nearly 35)

24. Edwards Syndrome

25. Viability in Human Aneuploidy (ex: 2n+x, 2n-x)
Reduced viability (survival) of persons born with monosomic or trisomic autosomal conditions
Significant percentage of spontaneously aborted fetuses are trisomic for an autosome (Carr study, 1971)
Virtually all possibilities found
Few monosomic autosomes found
Most are usually terminated much earlier in development
Some polyploid examples found

26. More From the Carr Study
15-20% of all pregnancies terminate by spontaneous abortion
About 30% of these have chromosome abnormalities
0.20 x 0.30 = 0.06 so up to 6% of all pregnancies originate with an abnormal number of chromosomes in the zygote
New data sets this rate as high as 1—30%

27. More Still… Highest percentage are aneuploid (2n +1, 2n-1)
Most common is 45,X
(would be Turner syndrome)
70% of these have maternal X
Most involve failure during spermatogenesis

28. Turner Syndrome Monosomy X

29. Triplo X (XXX) Result of Nondisjunction taller than average
typically causes no unusual physical features associated with an increased risk of learning disabilities
delayed development of speech and language skills
Seizures or kidney abnormalities occur in about 10 percent of affected females

31. XYY extra copy of the Y chromosome in each of a male's cells
Result of non-disjunction
This condition occurs in about 1 in 1,000 newborn boys
taller than average
typically causes no unusual physical features
increased risk of learning disabilities and delayed development of speech and language skills.
Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), hand tremors or other involuntary movements (motor tics), and behavioral and emotional difficulties are also possible

33. Polyploidy in Plants Multiples of a genome 3n, 4n, 5n, etc.
Relatively infrequent in animals
Mostly in lizards, amphibians and fish
Even numbers of sets generally more stable and therefore more common
Types
Autopolyploidy – multiples of the same genome
Allopolyploidy - multiples of different genome

34. Autopolyploidy
Each additional set of chromosomes is identical to the parent species
Mole Salamander, Wheat, human liver, apples and bananas
Origin
Complete failure to segregate during meiosis (first or second division nondisjunction)
Multiple sperm fertilize an egg
Triploids created by crossing diploid with tetraploid
Experimentally produced by cold or heat shock during meiosis

35. Mole Salamander

36. Experimentally Produced Tetraploids
Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison

37. Allopolyploidy Multiples of different genomes
Can occur through hybridization of two “closely” related species
Allotetraploid an interspecific hybrid having a complete diploid chromosome set from each parent form —Also called Amphidiploid
Cabbages and mustard

39. Allotetraploid Formation
Gametes fuse
DNA replication with subsequent cell division to form nonsterile hybrid
Normal mitosis and meiosis

40. Endopolyploidy
Only certain cells of an otherwise diploid organism are polyploid
Some human liver cells are 4n, 8n or 16n
Some apical region tissues of plant
Gut lining of mosquitoes can be 16n
Some tissues of insects in genus Gerris (water strider)
Up to 2048 copies of genome (2n = 22 so some cells have 40,000+ chromosomes)

41. Chromosome Rearrangements
Types
Deletions
Duplications
Translocations
Reciprocal
Nonreciprocal
Most involve one or more breaks in the DNA/chromosome
Broken ends lack telomeres and can be “sticky”
Can rejoin with other ends

42. `

43. Consequences of Rearrangements
Are heritable to daughter cells
And if in germ line to subsequent generations
Balanced translocations may not impact individual greatly
But gamete production will create defective cells/zygotes with predictable frequency
Gene dosage
Pairing problems during meiosis

44. Deletions Deletions Terminal deletions remove end of chromosome
Often a result of DNA damage involving strand breakage
Intercalary deletions delete an interior portion
Only portion retaining centromere will be maintained in daughter cells
Synapsing with normal chromosome creates a deletion loop or compensation loop visible during meiosis
Crossover between direct repeats can result in an internal deletion

46. Compensation Loop in a Polytene Chromosome
Creates a partially hemizygous condition and results in a phenomenon called pseudodomince

47. Duplications
Section of chromosome occurs more than once in a haploid equivalent (genome)
Commonly arise from unequal crossing over
Important evolutionary process
1970 Susomo Ohno – “Evolution by Gene Duplication”
Gene duplication produces a reservoir of genes from which to evolve new ones
Why reinvent the wheel from scratch?

48. Unequal Crossing Over

49. Position Effects
Bar-eye phenotype in Drosophila

50. Gene Duplication and Evolution
Yeast genome has about 5000 genes with about 55 duplicated regions that encode 376 pairs of duplicated genes
Humans have 1077 duplicated blocks of genes, with 781 having 5 or more copies of the duplicated segment
Make up nearly half of chromosomes 18 and 20

51. Chromosomal Inversions
No loss of genetic information (nucleotides)
Crossover between inverted repeats
Segment is inverted 180 degrees in chromosome

52. Chromosomal Inversions
Paracentric inversion does not involve centromere
Pericentric inversion involves centromeric region

53. Inversions and Gametogenesis
One member of homologous pair has inversion
Normal pairing during meiosis not possible
Inversion loop forms
When no recombination (process by which genetic information is broken and rejoined) occurs, 50% of gametes have inversion
But recombination can occur…

54. Inversions and Gametogenesis
Can break genes
May cause position effects
Especially if transported to position near heterochromatin (white eye in Drosophila moved to near centromere)
Major problems with recombination
Meiosis/mitosis
Acentric chromosomes – no centromere
Dicentric chromosomes – two centromeres
On the plus side…
Inversions can stabilize a good combination of alleles by blocking crossovers that would separate them

55. Inversions and Recombination
Many defective gametes can be produced

56. Translocations
Reciprocal translocations result from crossover events between nonhomologous chromosomes
Balanced translocation condition may result
Semisterility (50%)

57. Familial Down Syndrome
Robertsonian translocation or centric fusion
Fusion of the Q arms of two
acrocentric chromosomes
(13,14, 15, 21 and 22)
P arms lost (no centromeres)

58. Familial Down Syndrome
Most of Q arm from chromosome 21 translocated to 14 (14/21 translocation)
Fusion occurs at two rDNA regions on the chromosomes
About 20% rDNA copies lost
Carrier still normal

59. Fragile Sites
There are some mutant/fragile sites on chromosomes where chromatin fails to become properly compacted
Areas often subject to breakage
Can be associated with mental retardation and cancer

60. Fragile X Syndrome 1/4000 males, 1/8000 females
Dominant, not fully penetrant
Folate-sensitive (water-soluble B vitamin that occurs naturally in food ) site on X chromosome
Breakage more likely when cells grown under folate deficiency conditions
FMR1 (fragile X mental retardation gene)
many CGG tandem repeats
6-54 is normal, is a carrier (and unstable– genetic anticipation), above 200 expresses syndrome
Male offspring more likely to receive expanded locus than female offspring

61. Fragile X Chromosomes