what is a chromosome?
- consists of DNA and protein
- human autosomal cells (somatic cells) - diploid
- gametes - haploid
- 23 different chromosomes
- – somatic cells - 2 copies of 1-22 and XX or XY (diploid)
- – gametes - 1 copy of 1-22 and X or Y (haploid)
the sex chromosomes
male - heterogametic - XY
female - homogametic - XX
genotype vs phenotype
- genotype is the allele configurations in the DNA (D,d)
- phenotype is the characteristics displayed
X inactivation
- one of the copies or the X chromosome in females is inactivated
- occurs in early embryonic life
- silenced by it being highly compacted so that it has heterochromatin
- forms barr bodies
The cell cycle
G1 phase - carries out normal metabolism S phase - DNA replication and chromosome duplication - replication or each chromosome yeilds 2 identical chromatids G2 phase - cell prepares for mitosis M phase - mitosis
stages of mitosis
Prophase
- chromatid fibres more tightly coiled, condensing into a tight chromosome
- formation of mitotic spindle
Prometaphase
- nuclear membrane broken down
- sister chromatids attach to u-tubules
Metaphase
- chromosomes align in the spindle
Anaphase
- sister chromatids separate to the poles
Telophase
- chromatids cluster at poles
- two daughter nuclei form around clusters
- cytokinesis then causes the division of the cytoplasm to for two daughter cells (each with 46 chromatids) (exactly the same as initial cell except chromatids not paired)
stages of meiosis I
Prophase I - homologous paris of chromosomes associate and align - chiasmata form (X shape) - spindles formed - u-tubule attaches to kinetochorse Metaphase I - chromosomes align in the spindle Anaphase I - chromosomes separate towards poles - homologues separated Telophase I - chromosomes cluster at poles - nuclear membrane formed and cytokinesis occurs - 2 haploid cells formed (with 23 chromosomes)
stages of meiosis II
Prophase II - spindle formed Metaphase II - chromosomes align in spindle Anaphase II - chromosomes seperate and into chromatids and move towards poles Telophase II - chromatids cluster at poles - nuclei form and cytokinesis occurs - 2 haploid cells created (with 23 chromatids)
non-disjunction in meiosis
- incorrect separation of chromosomes or chromatids in meiosis I or meiosis II
- leads to aneuploidy
down syndrome
- incorrect separation of chromosome 21
- characteristic phenotype
- – poor muscle tone
- – mental retardation
Klinefelter syndrome
- incorrect separation of XY chromosome
- has both female and male traits
three stages of gene to protein
DNA (gene) --- TXN mRNA --- splicing and processing Mature mRNA --- TLN Protein
Transcriptional-level control of gene expression
Promoters
- additional proteins (TF’s) influence RNA polymerase binding and action (eg. TATA Box)
- TF’s are responsible for physiological change
- can either have a negative or positive effect
Enhancer regions
- sites on the DNA
- loop DNA to bring a specific promoter to the initiation complex
Translational-level control of gene expression
Hairpin
- structures that allow mRNA to twist tightly
- will hinder the ability for a ribosome to attach to mRNA as they are quite large
- can also be a binding sight for an interactive protein that will influence the ribosome
- however these structures will allow mRNA to live longer in the body
- eg: IRE with an IRP
- – attach to a hairpin
- – when enough iron attaches to IRP it leaves
- – the ribosomes can attach
DNA mutations
Processing errors - mistakes by topoisomerase - errors in DNA replication DNA damage - deamination --- removal of amino group --- happens often but is stopped - depurination --- incorrect base can be added to DNA
Types of mutations in the coding region
synonymous - no change - can create a codon that is rarely seen therefore slow for tRNA to produce it (condon bias)
non-synonymous - different amino acid
nonsense - create STOP instruction
frameshift - removing/adding nucleotide
types of mutation in non-coding regions
- promoter and enhancer regions
- 5’ and 3’ untranslated regions
- introns
Autosomal dominance
- mutant allele will causes disease or prevent other allele function
- only one dominant allele required to give disease
Autosomal recessive
- often mutation equates to loss of function
- need to have 2 recessive to show disease
X-linked dominant/recessive
- special consideration as male only have one X chromosome
- if mutant allele, you have to use it
- effected fathers never pass to son as they get the fathers Y and mothers X
SOME CAVEATS (exceptions)
germline mosaicism
- mutation arises during development - germ cells mutant
reduced penetrance
- disease causing genotype but no symptoms
age-dependent penetrance
- symptoms take lengthy time to rise (huntington’s)
