Chapters 3 and 7 multiple choice quizzes Due Monday 924 at midnight

1
Assignments

• Chapters 3 and 7 multiple choice quizzes (Due
  Monday 9/24 at midnight)
• Bioinformatics assignment (Handout) details later
  in class (Due Thursday 9/27 IN CLASS)

Notes changes in syllabus, exam time
2
Human Genetics Assignment

• Genetics Home Reference (NIH)

3
Chromosome Reproduction and Inheritance (Part
2)Variation in Chromosome Structure and Number

• Chapter 3
• Chapter 8

4
Gametogenesis

• Required for the formation of gametes
• Gametes are haploid, possessing one half the
  amount of genetic material (1n) as somatic cells
  (2n)
• Gametes are fused during fertilization
• Species in which all gametes are phenotypically
  similar - isogamous (Ex. Fungi, algae)
• 2 morphologically distinct gametes- heterogamous

5
Eukaryotic gametes

• Sperm
• Motile- often flagellated
• Small
• Egg
• Also referred to as ovum
• Usually large and nonmotile

6
Meiosis

• 1 round of replication, followed by 2 rounds of
  cell division
• Key distinction Meiosis 1 centromeres remain
  intact
• Steps
• Early prophase 1 Prophase II
• Late prophase I Metaphase II
• Prometaphase I Anaphase II
• Metaphase I Telophase II and
• Anaphase 1 cytokinesis
• Telophase I and
• cytokinesis

7
Prophase I
8
Prophase I

• Leptotena (leptotene)
• Chromosome condensation
• Visible with the light microscope
• Zygotena
• Homologous chromosomes recognize one another
• Aligned across the length
• Form bivalents (2 pairs of sister chromatids- 4
  chromosomes)
• Process called synapsis

9
Synaptonemal complex

• Aligns homologous chromosomes
• Composed of parallel lateral elements bound to
  DNA
• Central element promotes binding of lateral
  elements to each other by transverse filaments

10
Role of synaptonemal complex

• 3 possibilities
• 1. Help maintain homologous pairing
• 2. May participate in meiotic chromosome
  structure
• 3. Regulated crossing over

11
Cross-over

• Number of crossovers for each chromosome differ
  depending on length of chromosome and species
• Region of a crossover is called a chiasma (pl.
  chiasmata)
• Cross-overs have occurred by the end of pachytena

12
Diplotena/ Diakinesis

• Synaptonemal complex breaks down, non-sister
  chromatids remain closely associated at the
  chiasma
• Bivalent is visible by microscopy
• 4 chromosomes that are associated called a tetrad
• End of Prophase I, nuclear membrane breaks down

13
Metaphase I

• Homologs arrange at a metaphase plate
• Kinetochore microtubules attach to from sister
  chromatids to cellular pole

Metaphase (mitosis)
Metaphase 1 (meiosis)
14
Anaphase I/ Telophase I

• Two pairs of sister chromatids separate, and
  joined pair migrate to either pole
• De condensation occurs (in some species), and
  nuclear membranes re-form

ORD cohesion
Synaptonemal complex
Bickel et al. 2002 (Drosophila)
15
Result of Meiosis I

• 2 cells, each with pairs of sister chromatids
• These cells are still considered haploid, since
  they do not have pairs of homologous chromosomes
• Cells undergo cytokinesis, and are ready for
  meiosis II

16
Meiosis II

• Genetic material is result of meiosis I, pairs of
  sister chromosomes
• Prophase, metaphase, anaphase, and telophase are
  similar to that observed during mitotic division

17
Mitosis vs. Meiosis

• Mitosis
• Homologous chromosomes do not pair
• Sister chromatids attach to opposite poles
• 2 diploid daughter cells
• Cells are genetically identical

• Meiosis
• Homologous chromosomes pair (synapse)
• Homologous chromosomes attach to opposite poles
  during metaphase I
• Anaphase I, no separation of centromeres
• 4 haploid daughter cells
• Not identical cells
• Each cell has one homologous chromosome from each
  pair

18
Mitosis vs. Meiosis

• Mitosis

• Meiosis

2n
2n
2n
1n
19
Spermatogenesis vs. Oogenesis

• Spermatogenesis
• Spermatagonial cell divides to produce primary
  spermatocyte
• Spermatocyte undergoes meiosis I and meiosis II
• Result is 4 spermatids (haploid)

• Oogenesis
• Primary oocytes are produced before birth
• Oocytes are arrested at prophase I until sexual
  maturation
• Meiosis produces only one egg cell and 3 polar
  bodies

20
Spermatogenesis vs. Oogenesis
21
Meiosis segregation of homologs
22
Random bivalent alignment independent assortment
23
Sex determination

• Humans have X - Y sex determination
• Male is heterogametic sex (2 types of gametes-
  one carrying X, one carrying Y)
• Female is homogametic (all eggs carry X)
• Presence of the Y chromosome causes maleness
• XXY- male

24
Other sex determination mechanisms

• Drosophila and other insects X-0
• Female XX, Male X0
• Ratio between X chromosomes and autosomes that
  determines sex (2n to 1 X 0.5 male)
• Birds and Fish Z-W
• Males ZZ
• Females ZW
• Bees haplo-diploid
• Male bees are produced from unfertilized haploid
  eggs
• Female bees are produced from fertilized eggs,
  are diploid

25
Sex chromosomal inheritance (3A)

• Thomas Hunt Morgan- raised flies in the dark-
  will the eyes atrophy?
• After many rounds of breeding and mutation with
  X-rays and radium, obtained a white-eyed male
• Bred the white eyed male to a red eyed female,
  result all red eyes (F1)
• Interbreed F1 to obtain F2, and performed a test
  cross

26
Inheritance pattern of X linked trait
XwY , XwXw
XwY , XwXw
Xw Y, XwY , XwXw , XwXw
XwY , XwXw
TESTCROSS
XwY , XwY, XwXw, XwXw
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Inheritance pattern of X linked trait
XwY , XwXw
XwY , XwXw
Xw Y, XwY , XwXw , XwXw
1011 782 2459
DATA
XwY , XwXw
TESTCROSS
XwY , XwY, XwXw, XwXw
132 86 129 88
DATA
28
X-linked reciprocal crosses

• Transmission pattern of traits may depend on the
  sex of the parent

Male Xw Y (red eyed) Female XwXw (white eyed)
Male Xw Y (white eyed) Female XwXw (red eyed)
Xw
Y
Xw
Y
Xw
Xw
Xw
Xw
29
Transmission of genes on sex chromosome

• X- linked
• Hemizygous genes on only X, not Y (male, single
  copy)
• Y- linked
• Holandric genes genes only located on Y
  chromosome (ex. Sry in humans)
• Pseudoautosomal
• Genes located on homologous region of X and Y

30
Transmission of genes on sex chromosome
31
Chromosome structure

• Physical features
• Number
• Size
• Location of centromere
• G banding pattern

32
Chromosome number

• Vary by species

Human 23 pair Drosophila 4 pair Corn 10 pair
33
Chromosome nomenclature

• Convention is to number chromosomes by size
  largest 1 . . .

34
Chromosome nomenclature

• Divided into P and Q sections
• P above the centromere
• Q below the centromere
• Sections are further numbered (give genes an
  address)

35
G banding patterns

• Treat with Gimesa stain
• Observe banding pattern (light and dark bands)
• Banding pattern differs depending on cell phase
• Mid-metaphase vs. prophase

36
How banding patterns are used

• Tell chromosomes apart (hu. Ch. 8 and 9)
• Detect changes in chromosomal structure
• Observe rearrangements or changes in total number
  of chromosomal material

37
Changes in chromosome structure

• Deficiency
• Segment of chromosome is missing (aka deletion)
• Duplication
• Section of chromosome is repeated

38
Changes in chromosome structure

• Inversion
• Change in direction of genetic material on
  chromosome
• Simple translocation
• One segment of chromosome becomes attached to
  another chromosome
• Reciprocal translocation
• Two types of chromosomes exchange pieces

39
Chromosomal deficiency

• Terminal deficiency (end breaks off- degraded)
• Interstitial deficiency (break in two locations,
  outer fragments re-attach to each other)

40
Detect deficiency

• Microscopically (aka cytogenetically)
  large chromosomal deletions
• In situ hybridizations
• Genetic analysis

41
Duplications

• Chromosome carries extra genetic material
• The larger the duplication, the more likely there
  will be phenotypic consequences
• Charcot-Marie-Tooth disease (type 1A) - causes
  numbness in extremities
• Due to duplication on chromosome 17

42
Mechanism of duplication

• Due to abnormal recombination- misalignments
• Can result in one chromatid harboring a
  duplication, while the other chromatid has a
  deletion (the details of crossing over, etc. will
  be covered later)

43
Discovery of gene duplications Exp. 8A

• Drosophila studies revealed eyes with a reduced
  number of facets
• Called bar eyes
• X linked trait
• Incomplete dominance (females homozygous for
  ultrabar allele has fewer facets than a female
  that is heterozygous for ultrabar and WT)
• What causes the bar alleles?

44
Examination of chromosomes

• Difficult to see differences in one allele by
  microscopy
• Utilize polytene chromosomes
• Example of polyploidy (changes in number of
  chromosomal sets)
• Example of alterations in chromosome number

45
Changes in single chromosomes

• Anuploidy- change in one chromosome of a pair
• Trisomy (2n 1) - three of a chromosome
• Monosomy (2n -1)- only one chromosome

46
Consequences to anuploidy

• Often abnormal phenotype due to change in
  expression level (50 or 150 of gene expression)
• Example of visible trisomic phenotypes in the
  Jimson weed

47
Human anuploidy

• Syndromes result from trisomy of chromosomes 21,
  18, 13, or alterations of sex chromosome number

Smaller chromosomes
Why are variations in number of X chromosomes
often non-lethal? Then why are there phenotypes?
48
Possible cause of human anuploidy

• Anuploid occurrence rates increase in older
  parents
• Down syndrome (Trisomy 21) is often a result of
  non-disjunction during meiosis 1
• Primary oocytes, arrested in prophase I, may age,
  and cause improper segregation
• Only 5 of Down syndrome cases are due to extra
  paternal chromosome 21

49
Changes in numbers of chromosome pairs

• Euploidy chromosome number is an exact multiple
  of a chromosome set
• Diploid (2x) 2 sets of chromosomes (ex.
  Drosophila typically has 2 sets of 4 chromosomes)
• Triploid (3x)(ex. Drosophila can have 3 sets of 4
  chromosomes) still euploid
• Polyploid- other multiples (often observed in
  plants)

50
Plant euploidy

• Ferns and flowering plants are 30-35 euploid
• Can confer increased size and robustness to a
  plant
• Odd numbered -ploids are often sterile due to
  unequal anaphase I
• This sterility can result in seedless fruit

51
Endopolyploidy

• When tissues of organism have cells with variable
  number of chromosome sets
• Observed in the human liver
• Can be tri, tetra, even octapolid
• Reason for this unclear (need to produce more
  proteins in specific tissue)
• Cells of the Drosophila salivary glands have 512
  chromosomes, due to 9 rounds of doubling without
  division

52
Polytene chromosome

• Following the 9 rounds of replication,
  chromosomes bundle, lying in parallel

53
Polytene chromosome

• In Drosophila, there are 4 pairs of chromosomes
  that form 4 polytene arms surrounding
  chromocenter
• Attach to chromocenter by centromere (remember
  telocentric vs. metacentric)
• Polytene chromosomes have characteristic banding
  patterns
• Used to study chromosomal alterations (visually)

54
Back to bar eye phenotype

• Various phenotypes and genotypes of bar allele

Examination of true breeding bar flies revealed
both revertants and as well as ultrabar
phenotypes - in equal numbers
55
Experiment

• Examine bar, revertants and ultrabar polytene
  chromosomes in salivary glands
• View banding patterns of polytene chromosome
  (known to be on region 16A)

56
Result

• Formation of bar allele is due to a cross over
  misalignment
• In true breeding bar strain, misalignment can
  occur an additional time during oogenesis,
  causing ultra bar and WT reversion

57
Duplications can lead to homologous gene families

• Small changes in chromosomes can lead to
  gathering of multiple mutations over generations
• Homologs are derived from single ancestral gene
• Gene family within a species paralogues
• Ex. Globin family of genes

58
Evolution of the globin gene family

• Proteins involved in oxygen binding
• Duplication and rearrangements resulted in 14
  globin genes on 3 chromosomes
• Family members are specialized for various jobs
  (working in muscle or blood)

59
Consequence of inversions

• Types of inversions
• Pericentric inversion
• Paracentric inversion
• Do not always cause phenotypic changes (same
  amount of genetic material
• Heterozygotes with one copy of an inverted
  chromosome are likely to produce haploid cells
  with major chromosomal abnormalities

60
Formation of inversion loops
Will be degraded
Will break at the dicentric bridge
61
How translocations occur

• Following chromosomal breakage, DNA can repair
  chromosomes incorrectly, attaching mismatched
  chromosomes
• Abnormal crossover between non-homologous
  chromosomes

62
Balanced/unbalanced translocation

• Balanced translocation result of non-homologous
  crossover/ reciprocal translocation
• Unbalanced translocation can result from
  inheritance of chromosomes that have been
  mis-repaired
• Familial Down syndrome
• 2 normal copies of chromosome 21
• Almost 1 full copy of chromosome 21 attached to
  chromosome 14
• Example of Robersonian translocation

63
Robertsonian translocation

• Breaks at extreme ends of non-homologous
  chromosomes (acrocentric)
• Acentromeric segments lost, centromeric fractions
  fuse at centromeric regions (becoming
  metacentric/ submetacentric)

64
Abnormal gametes due to balanced translocations

• Reciprocal translocations may not have
  phenotypes, but gametes may be formed incorrectly
• Pairing of homologous regions during meiosis
  cause 4 pairs of sister chromatids to form
  translocation cross
• Segregation of the cross during anaphase one can
  occur in three ways
• Alternate segregation
• Adjacent-1 segregation
• Adjacent-2 segregation (both copies of centromere
  1 goes to the same daugher cell)

65
Translocation cross
66
Meiosis products of reciprocal translocations

• Result of Adjacent 1 and Adjacent 2 is 4
  unbalanced gametes
• Many are not viable, and cause a lowered
  fertility (known as semisterility)
• Often observed in plants (due to self
  fertilization)
• corn ears with missing kernels

67
Nondisjunction

• Meiotic nondisjunction lack of proper
  chromosomal segregation during anaphase
• Caused by either
• Improper separation of homologous pairs
• Failure of centromeres to disconnect during
  meiosis II or mitosis
• Result gametes with too many or too few
  chromosomes (polyploidy or anuploidy)

68
Meiotic nondisjunction
69
Mitotic nondisjunction

• Occurs in somatic cells
• Can also have chromosomal loss (no attachment to
  spindle)
• Results in chimeric tissue with variable
  chromosomal content (and sometimes expression)
• Ex. Drosophila in which one X chromosome is lost
  during the first mitotic division 1/2 male 1/2
  female
• Bilateral gynandromorph

female
male
70
Alloploid

• Alloploid- result of mixing species
• Allodiploid- one set of chromosomes from 2
  species
• Allotetraploid- 2 complete sets of chromosomes
  from 2 species
• Interbreeding more successful with organisms
  having same number of chromosomes, similar size