Lecture 5 - Genome Anatomy Flashcards
Where is almost all heritable information written?
DNA sequences (3 x10^9 nt)
Where else can written information be stored in the body?
Epigenetics
Why is genetic information stored in DNA?
When sugar is incorporated into the DNA structure (backbone) it gives it a very supported structure (stable) so it is easily extractable.
Which direction is DNA written in?
DNA sequences are written in a 5´ → 3´ direction
This is the direction in which DNA and RNA are synthesized
Which strand would usually be written/ transcribed?
Sense strand
Why is it harder to copy the other DNA strand?
Because DNA can only be written in a 5’ to 3’ direction therefore the other strand runs in an opposing direction therefore RNA primer has to be involved and Okazaki fragment to be joined after the RNA primer is removed. (Multi step process)
How accurate is human DNA replication?
Every person has 12 new mutations
Where do significant errors of the human body occur in the genome?
Exons
What percentage of the genome do exons occur?
2%
What is achondroplasia?
A type of bone growth disorder. Due to genetic mutations, the cartilage does not convert into a bone during foetal development, resulting in dwarfism
What percent of the time is a condition (Achondroplasia) due to a new mutation rather than inherited?
80%
What happens when you get to the end of the chromosome?
Telomeres - holds chromosome intact so can be copied almost up to end of chromosome
TTAGGG telomeric repeat sequence
Specialized replication machinery
Telomerase, TERT
Inactive in somatic cells
Why would someone older than you have shorter telomeres?
Telomeres shorten with somatic cell division
Finite number of cell divisions to senescence
When would someone older than you having shorter telomeres not be the case?
TERT reactivation in cancer
What is the relationship between DNA and chromesomes?
Packaging relationship (So they can fit into the nucleus of cells)
What is a nucleosome?
Carries around 200 base pairs of DNA wrapped around it with a histone core.
what is a centromere?
Middle of a chromosome holding the two chromatids together
what is a p telomere?
Two short arms
What is a q telomere?
Two long arms
What is a chromosome ideogram?
Idiogram is the diagrammatic representation of karyotype showing all the morphological feature of the chromosomes grouped on the basis of position of centromere and ordered in a series of decreasing size. Chromosome banding and painting technique are used to identify each chromosome.
what are chromosome coordinates?
Sequence that has been ordered and oriented on the chromosome. The locations of these sequences can usually be expressed in chromosome coordinates. A sequence found in an assembly that is associated with a specific chromosome but cannot be ordered or oriented on that chromosome.
What is the issue with chromosome coordinates?
There is no single correct version of the entire genome.
Genetic reports must specify the version of the reference genome being used.
What is the chromosome complement?
The chromosome complement is diploid
n = 23
2n = 46
DNA content (3×109 bp)×2 = 6×109 bp
Two copies of every gene (pat, mat)
what is gene dosage?
Gene dosage is the number of copies of a particular gene present in a genome. Gene dosage is related to the amount of gene product the cell is able to express. However, the amount of gene product produced in a cell is more commonly dependent on regulation of gene expression.
What is Haploinsufficiency?
A situation in which the total level of a gene product (a particular protein) produced by the cell is about half of the normal level and that is not sufficient to permit the cell to function normally.
Always a problem for whole chromosome.
For many individual genes as well.
Which chromosome bigger X or Y?
X (Contains many more important genes).
women have more double of important genes
What is dosage compensation
the genetic mechanism by which the same effect on the phenotype is produced by a pair of identical sex-linked genes in the sex (as the human female) having the two sex chromosomes of the same type as by a single gene in the sex (as the human male) having the two sex chromosomes of different types or having only one sex chromosome (as in the males of some insects)
What is the SRY on the Y chromosome?
Sex determining region - tells embryo to make testis
Do all organisms have the same size genome?
No
How are the chromosomes ordered?
From biggest to smallest
Is most of our DNA coding or non- coding?
Non - coding >90%
How many Mbp dsDNA per hapoid genome?
3000
How many protein coding genes are there?
20000
What is the average gene size?
50-100kb
What is the average mRNA size?
2 kb
what are characteristics of the michocondrial genome?
Circular not linear
Endosymbiotic remnant
16 kb, 37 genes
rRNA, tRNA, ox-phos
Cytoplasmic not nuclear
Maternal (oocyte) inheritance
Own tRNA
What are the different sequence classes of the human genome?
Single-copy sequences (non-repetitive)
(Genes)
Repetitive sequences
(“Satellite” DNA)
(Large blocks of repetitive sequence)
(Heterochromatin)
(Interspersed repeats
e.g. Alu repeats)
What are characteristics of genes?
Functional units of DNA
Genes are expressed
Some place, some of the time
Transcription – copying into RNA
Translation – turning RNA into protein
Not all
Short and long non-coding RNAs inc. miRNAs
Components
Exons
Introns
Regulatory sequences
Promoters, enhancers, locus control regions
What is an exon?
a segment of a DNA or RNA molecule containing information coding for a protein or peptide sequence
What is an intron?
a segment of a DNA or RNA molecule which does not code for proteins and interrupts the sequence of genes
What are the steps of DNA replication?
- Transcription (RNA polymerase)
- Cleavage and polyadenylation
- Splicing
- Transcription
- Posttranslational Modification
What is alternative slicing?
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands.
What are gene families characteristics?
Evolution of genes progresses by duplication and divergence
Most genes belong to a family of structurally related genes
Members of a gene family may be clustered or widely dispersed
Pseudogenes
How are pseudogenes formed?
- ancestral gene
- duplication
- divergence
- Psuedogene
What is a pseudogene?
a section of a chromosome that is an imperfect copy of a functional gene.
What are the divisions of the human genome?
Coding genes: 20,000
Long non-coding genes: 16,000
Other non-coding RNA genes: 4,000
Pseudogenes: 14,000
Coding gene transcripts: 90,000
What are processed genes?
Intronless copies of other genes
Usually remote from parent gene
Reverse transcription and reintegration
cf. retroviruses
Occasionally remain functional
e.g. PGK2 (testis-specific)
Most are non-functional
How do processed genes form?
- ancestral gene
- mRNA
- Reverse transcription
- Reintegration
- Processed gene
- Mutation
- Processed psuedogene
Characteristics of repetitive genes?
“Satellite” DNA
(Large blocks of repetitive DNA sequence)
Interspersed repeats
(Scattered around the genome)
what is satellite DNA?
Large blocks at centromeres and heterochromatic chromosomal regions
Simple tandemly repeated sequences
(Many types e.g. alphoid DNA
Centromere repeat
Chromosome-specific)
Size of blocks may be polymorphic
(1, 9, 16, Y)
What is alphoid DNA?
A type of satellite DNA found at centromeres
171-bp repeat unit
Repeat unit sequence shows chromosome-specific sequence variation
(Probes for individual chromosome identification (FISH))
Alphoid DNA is required for assembly of the centromere
What are interspersed repeats?
Scattered around the genome
Individual copies are present at many locations
(Maybe between or within genes)
Example: Alu repeat (a SINE)
Short interspersed nuclear element
500 000 copies × 300 bp = 5% of genome
Dispersed by retrotransposition
Role in generation of molecular pathology
