Lecture – Introduction
Genetics – Single Genes
Genomics – All (/many different) genes at once
Fundamental Aspects of Genomic Technologies; (Epi)Genetic bases of diseases; Technologies for the clinic, and
scientific or forensic research.
Lecture-1: Chromosomal Translocations
TKIs, Translocations, Rearrangements, Chromosome Structure, Giemsa, C
Lecture-2:
Lecture-3:
Lecture-4:
Lecture-5:
Lecture-6:
Lecture-7:
Lecture-8:
Lecture-9:
Lecture-10:
,Lecture – Translocation/Gene Rearrangements
Philadelphia Chromosome: Recombination of Chromosome (q)9 and (q)22
Chromosomal Translocations: Rearrangement of chromosomal segments that may cause alteration in gene
expressions, either because of promotors or gene-fusions
Cleavac: Kinase Inhibitor that prevents phosphorylation of the Philadelphia Gene fusion product
Philadelphia Chromosome: Gene Fusion that leads to hyperactivation of BCE-ABL because of phosphorylation
CML: Chronic Myeloid Leukaemia
Eight Histones and a 147bp oligonucleotide stretch form nucleosomes to form Beads-on-a-String, and may be
further coiled by Histone-H1 to form a 30nm-Fibre, etc.
,200bp Oligonucleotides for linker-DNA (~53) + Nucleosome wounded DNA (147)
Histone Modifications: Acetylation, phosphorylation, methylation, ubiquitination, etc.
Mitosis Phase for Karyotyping; Giemsa
Staining to characterise chromosomes
into pairs
KARYOTYPING IN METAPHASE
, Reciprocal (Balanced) and Robertsonian Translocations:
➔ P(etit)- and Q-Arms
➔ Reciprocal: Balanced Translocation of similar (Q or P) arms among different chromosomes; Robertsonian
Translocation: The Q-arm of one chromosome with the P-arm of another chromosome is translocated,
possibly leading to the loss of an a two-p-arm chromosome
➔ Balanced Rearrangement: Same amount of DNA/Genes before and after the arrangement
Unbalanced Rearrangement: Deletions may cause extensive loss of genetic material
PRIMARY OR SECONDARY EVENTS??
Conventional Karyotyping: G-Banding:
Advantages:
- Global Genetic Information
- Variants Uncovered (undetectable by FISH and RT-PCR)
- Provides directions for further molecular studies
Disadvantages:
- Requires fresh tissue
- 1-10 day cell culturing
- Complex karyotypes
Genes might gain novel CREs (promotors/enhancers) due to translocations, or gene fusion might occur that forms
novel proteins that are suddenly more active
Genetics – Single Genes
Genomics – All (/many different) genes at once
Fundamental Aspects of Genomic Technologies; (Epi)Genetic bases of diseases; Technologies for the clinic, and
scientific or forensic research.
Lecture-1: Chromosomal Translocations
TKIs, Translocations, Rearrangements, Chromosome Structure, Giemsa, C
Lecture-2:
Lecture-3:
Lecture-4:
Lecture-5:
Lecture-6:
Lecture-7:
Lecture-8:
Lecture-9:
Lecture-10:
,Lecture – Translocation/Gene Rearrangements
Philadelphia Chromosome: Recombination of Chromosome (q)9 and (q)22
Chromosomal Translocations: Rearrangement of chromosomal segments that may cause alteration in gene
expressions, either because of promotors or gene-fusions
Cleavac: Kinase Inhibitor that prevents phosphorylation of the Philadelphia Gene fusion product
Philadelphia Chromosome: Gene Fusion that leads to hyperactivation of BCE-ABL because of phosphorylation
CML: Chronic Myeloid Leukaemia
Eight Histones and a 147bp oligonucleotide stretch form nucleosomes to form Beads-on-a-String, and may be
further coiled by Histone-H1 to form a 30nm-Fibre, etc.
,200bp Oligonucleotides for linker-DNA (~53) + Nucleosome wounded DNA (147)
Histone Modifications: Acetylation, phosphorylation, methylation, ubiquitination, etc.
Mitosis Phase for Karyotyping; Giemsa
Staining to characterise chromosomes
into pairs
KARYOTYPING IN METAPHASE
, Reciprocal (Balanced) and Robertsonian Translocations:
➔ P(etit)- and Q-Arms
➔ Reciprocal: Balanced Translocation of similar (Q or P) arms among different chromosomes; Robertsonian
Translocation: The Q-arm of one chromosome with the P-arm of another chromosome is translocated,
possibly leading to the loss of an a two-p-arm chromosome
➔ Balanced Rearrangement: Same amount of DNA/Genes before and after the arrangement
Unbalanced Rearrangement: Deletions may cause extensive loss of genetic material
PRIMARY OR SECONDARY EVENTS??
Conventional Karyotyping: G-Banding:
Advantages:
- Global Genetic Information
- Variants Uncovered (undetectable by FISH and RT-PCR)
- Provides directions for further molecular studies
Disadvantages:
- Requires fresh tissue
- 1-10 day cell culturing
- Complex karyotypes
Genes might gain novel CREs (promotors/enhancers) due to translocations, or gene fusion might occur that forms
novel proteins that are suddenly more active
