Chromosomal Abnormalities II Flashcards
What are the two translocations?
β Reciprocal
β Robertsonian
What are the 7 structural abnormalities?
β Translocation β Inversion β Deletion β Duplication β RIngs β Isochromosomes β microdeletions/microduplication
How do the structural abnormalities occur?
β Double strand DNA breaks
β occur throughout the cell cycle
β misrepair leads to structural abnormalities
How are double strand breaks usually repaired?
β DNA repair pathways
What is translocation?
β two double strand breaks each on a different chromosome
How do balanced translocations arise?
β DNA repair mechanisms stitch the chromosome in incorrect pairs
β there is no net loss or gain of genetic material it is just in a different place
What does der mean?
β Derivative
What is a balanced translocation?
β The right amount of each chromosome just in the wrong place
What is an unbalanced translocation?
β too much or too little of a particular chromosome
What is a Philadelphia chromosome?
β abnormal chromosome 22
What does the Philadelphia chromosome lead to?
β Chronic myeloid leukaemia
What is a BCR?
β Break point cluster region (function of normal protein is unknown)
What tends to happen in the BCR region?
β Tendency to have double stranded breaks
What is an ABL?
β a proto oncogene
What does fusion of genes in the Philadelphia chromosome lead to?
β An activated oncogene ABL
What is a reciprocal translation?
β exchange of two segments between non-homologous chromosomes
When does a deleterious phenotype occur?
β when the breakpoint affects the regulation of a gene
What is a carrier of a balanced translocation at risk of?
β producing unbalanced offspring
What are unbalanced individuals at significant risk of?
β Chromosomal disorder
Describe how an unbalanced individual with partial trisomy for chromosome 11 and partial monosomy for chromosome 22 arises?
β In the cell you have one copy of normal 11 and normal 22 and the two derivative chromosomes ( 22 with a piece of 11 and 11 with a piece of 22)
β In the gametes you want one chromosome 11 and one 22
β you can get the normal intact copies or the derivative copies
β if you inherit the normal copy of 11 (from both parents so you have 2 copies of 11) and the derivative copy of 22 with a piece of 11 on it during fertilisation
β there is an extra piece of chromosome 11 on the end of one of the 22 chromosome
β partially trisomic for chromosome 11
When do homologous chromosomes align?
β in metaphase 1
How do derivative chromosomes align with their homologs?
β They form a quadrivalent structure
β chromosomes are trying to find their partners so the pieces align with each other
β pulling apart can occur in 4 orientation
What can an unbalanced reciprocal translocation lead to?
β Miscarriage
β learning difficulties, physical disabilities
What should you do if thereβs a woman who has a high number of unexplained miscarriages?
β Screened for a balanced translocation
