Ames test Strains inactive for BER and prone

Ames test Strains inactive for BER and prone for entry if molecules TA 100 - sensitive for reversion by base pair substitution TA 1535/8 frameshift

מוטגנים Mutagens חומרים כימיים Chemical Agents קרינה Radiation ניידים DNA אלמנטים Mobile Genetic Elements

Barbara Mc. Clintock

Ds (Dissociation) Ac (Activator)

Insertion elements: insertion elements as mutagens gal- , due to insertion OR “disruption” REVERTANT: gal+ revertant, due to excision of IS 1

Simple transposon (Ampicillin resistance)

Composite transposon IS 10 (tetracycline resistance) IS 10

Conservative Replicative

Animation 13_Replicative transposition

Inexact excission of IS 1 can also create gal-

(Ampicillin resistance) -There are several different types of transposable elements including insertion elements (S 1, IS 2. . ) and transposons (Tn 1 Tn 2…) -Many transposable elements transfer a resistance for antibiotic -Most of the transposable elements have inverted repeats (IR) at the end which can be observed under the microscope -Transposable elements are found on chromosome and plasmids -After insertion into new site the elements generates a short repeats- Replecative vs. conservative -

• Transposons are much more common in eukaryotes. • Some eukaryote transposable elements transpose as in prokaryote but most use similar mechanism as the RNA viruses.

LTR- long terminal repeat

מוטגנים Mutagens חומרים כימיים Chemical Agents קרינה Radiation אולטראסגול Ultraviolet (UV) מייננת Ionizing ניידים DNA אלמנטים Mobile Genetic Elements

Rearrangements

Rearrangements

Human Karyotype Lyse Cell and its Nucleus Karyotype- The entire chromosomes complement of an individual Organism or cell, as seen during mitotic metaphase

Banding

SKY-Spectral karyotype

Chromocenter

D C E F B A F E A B

Since b+ and c+ are “missing”, the phenotype of b and c are “pseudo-dominant” or “display pseudodominance”: The genes ‘across from’ the deletion “display pseudodominance”.

Inversions: Animation 17. 1 a

Paracentric inversion does not span the • centromere Pericentric inversion does includes the • centromere

היפוכים Inversions

paracentric inversion

The trouble with paracentric inversion: Animation 17. 1 b

pericentric inversion

היפוכים Inversions x c. M y c. M No offspring are ‘counted’ when a crossover occurs in interval y- they all die map units look like x-y c. M SO – with a heterozygote for an inversion: The apparent genetic distance between genes outside the inversion seems to be reduced by y

Rearrangements

Duplications

Rearrangements

Human hemoglobin gene family: The result of a series of gene duplications, followed by gene divergence.

Thalassemias Thalassemia

Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia (CML). It is due translocation designated as t(9; 22)(q 34; q 11), The fused bcr-abl protein interacts with the interleukin 3 beta(c) receptor subunit. The bcr-abl transcript is constitutively active, i. e. it does not require activation by other cellular messaging proteins. In turn, bcr-abl activates a number of cell cyclecontrolling proteins and enzymes, speeding up cell division. Moreover, it inhibits DNA repair, causing and potentially causing the feared blast crisis in CML.

Trinucleotide repeats

Slippage during replication

Rearrangements

Reciprocal translocation chromosomes during meiosis: Animation 17. 2 b

Animation 17. 2 c Second genetic consequence of translocations: Pseudo-linkage

Human Karyotype – Trisomy 21 Lyse Cell and its Nucleus

Non-disjunction in Meiosis I: Animation 18. 1 a

Non-disjunction in Meiosis II: Animation 18. 1 b

Trisomy of 13 or 18 show severe physical and mental abnormalities Between few weeks and 130 days Patau Edwards Down

מונחים *Polyploids-individual with more than two • chromosomes sets. i. e. Triploids-3 n, tetraploid 4 n, pentaploid-5 n, hexa…. *Monoploid- one chromosome set (not a haploid) • *Autopolyploid (chromosomes within species) vs. • allopolyploids (chromosomes from closely related species) *Aneuploidy- chromosomes number is abnormal, i. e. • trisomic; 2 n+1, monososmic; 2 n-1 and nullsomic; 2 n-2. In haploid n+1 is disomic

Monosomy: Karyotype minus 1 chromosome homolog חסר עותק )הומולוג( אחד של כרומוזום Nullisomy: Karyotype minus both chromosome’s homologs שני העותקים )הומולוגים( של כרומוזום אחד חסרים

An example: In males X+Y X Y X+X X Y Y Y

An example: In females X 1+X 2 X 1+ X 2 X 1 + X 1 X 2 X 2

XXY - Kleinfeldter

XO - Turner

Animation 17. 2 c Second genetic consequence of translocations: Pseudo-linkage

X: A=1 X: A=0. 5 Sxlisis. On off Sxl Splicing of dsx Male specific genes

Y?

O/o O-Orange o-Black. The white phenotype is due to other gene

Sex-linked anhidrotic ectodermal dysplasia (absence of sweat glands in blue areas)

XXX, XXYY

מונחים *Polyploids-individual with more than two • chromosomes sets. i. e. Triploids-3 n, tetraploid 4 n, pentaploid-5 n, hexa…. *Monoploid- one chromosome set (not a haploid) • *Autopolyploid (chromosomes within species) vs. • allopolyploids (chromosomes from closely related species) *Homeologous- Partially homologous (common • ancestor) *Aneuploidy- chromosomes number is abnormal, i. e. • trisomic; 2 n+1, monososmic; 2 n-1 and nullsomic; 2 n-2. In haploid n+1 is disomic

Diploid

Polyploid Tetraploid

Octoploid

Generation of monoploid Cold treatment Embrioyoid-a small dividing mass of monoploid cells

Breeder – search for special phenotype of a/a b/b A/a B/b recombination ab Cold treatment monoploid colchicine Diploid

2 n 4 n

Aneuploid and gene balance Usually aneuploids are not viable or • severely affected due to changes in gene balance. In a euploid the ration between genes is 1: 1 whereas in aneuploid this balance is variable