Genetics Flashcards
Normal human karyotype
46 chromosomes - 2n (22 pairs of autosomes and a pair of sex chromosomes)
Chromosome structure
Each chromosome consists of a short (p) and long (q) arm joined at the centromere
Telomere
Telomere - seal ends of chromosomes and maintain structural integrity (repetitive sequence of thymine)
Telomerase replaces 5’ end of long strand during DNA replication making strand shorter until it can no longer divide
Chromosome classification
• centrally = metacentric
• terminal = acrocentric (13,14,15,21,22 - Robertsonian chromosomes)
• intermediate position = submetacentric
Mitosis
process by which chromatically separate and divide in to two separate cells
Usually lasts 1 to 2 hours
5 distinct stages: prophase, prometaphase, metaphase, anaphase and telophase
Prophase
chromosomes condense, mitotic spindle begins to form, two centrioles begin to form and move to opposite poles (microtubules begin to form from alpha/ beta tubulin)
Prometaphase
nuclear membrane disintergrates and chromosomes attach to microtubules by centromeres
Metaphase
chromosomes line along equatorial plate of cell to form mature spindle- chromosomes maximally contracted so visible X shape
Anaphase
centromere of each chromosome divides longitudinally and 2 daughter chromatids separate to opposite poles of cell
Telophase
2 groups of chromatids become surrounded by nuclear membrane
Cytokinesis
cell cytoplasm divides to form two new diploid daughter cells
Interphase
G1 - chromosomes become thin and extended (variable in length so accounts for change in generation time. Cells that have stopped dividing, e.g. Neurones, arrest in this phase = G0)
S - DNA replication occurs and the chromatin of each chromosome is replicated (homologous pairs replicate in synchrony but 1 of X chromosomes is always late as is inactive X chromosome that forms the sex chromatin which viewed in interphase of female somatic cell)
G2 - chromosomes begin to condense
Importance of mitosis
• producing 2 genetically identical daughter cells to parent cell
• growth
• replace dead cells
Clinical relevance of mitosis
• detecting chromosomal abnormalities
• categorising tumours as benign or malignant
• grading malignant tumours
Meiosis
the process of nuclear division that occurs in final stages of gamete formation
Prophase I
chromosomes are already split longitudinally into 2 chromatids joined at centromere. Homologous chromosomes pair (with exception of X and Y in males where pairing only occurs at tip of shorter arms called pseudoautosomal region) and crossing over may occur, exchange of non-sister chromatid alleles.
Metaphase I
the nuclear membrane disappears and chromosomes become aligned on the equatorial plane of cell- attached to spindle
Anaphase I
chromosomes separate to opposite poles as spindle contracts (independent assortment)
Telophase I
each set of haploid chromosomes separated so cleaves to form 2 new daughter gametes (secondary spermatocytes or oocytes)
Meiosis II
same as mitotic division to form 4 haploid (n) new daughter gametes (spermatids or ova)- genetically different
Preventing mutations during cell replication/division
• genetic material protected in stem cells as rapid cell division occurs in daughter cells not stem cells
• 3 checkpoints: at end of G1 restriction point, needs external growth factor for cell division to continue; in G2 checkpoint looks for damage and unreplicated DNA, can stop cell cycle and kill cell to prevent replication of mutated DNA controlled by P53 but gene for P53 is often mutated in cancer cells leading to uncontrolled cell division; S phase checkpoint by RPA protein itstabilises the replication fork and coordinates repair
3 Main differences between mitosis and meiosis
- Mitosis = diploid cells, meiosis = haploid cells
- Mitosis occurs in somatic cells and early stages of gamete formation, meiosis occurs only at final stage of gametic maturation
- Mitosis = one cell division, meiosis = 2 cell divisions
3 cell populations
• permanent cells- cells that never divide G0 eg neurones
• Labile cells- cells that constantly divide eg epidermis
• stable cells- spend most of time in G0 but can be induced to re-enter cell cycle eg liver cells
Stopping mitosis
Mitotic spindle - taxol or vinca alkaloids (vinblastine, vincristine)
Spindle poles- ispinesib
Anaphase - colchicine-like drugs- form ring structures