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Summary Genomic Architecture

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Summary of the Genomic Architecture course.

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16s rRNA – the RNA of the small subunit of a ribosome. This sequence is very
useful for prokaryote species identification. The reason for that is that this
sequence (including universal primers) is present in all known organisms
and is highly conserved in all specific species. There are differences in this
sequence between species, but almost no differences between individuals of a
species.
Ancient DNA – can be used to gain information about the origin, distribution,
evolution and more, of species. Disadvantages are that the aDNA is often
degraded, for example due to heath, and can be contaminated. Useful bones
are petrous bones (inside of the skull, dense bone, but no pathogen DNA), teeth
(enamel protects the teeth, root contains DNA and pathogens) and thick
bones with a large cortex. There are usually more mitochondrial DNA copies
(contain a high ratio of A-T) present than nuclear DNA copies, so, this is easier to
extract and analyse.
Backcrossing – the mating of a hybrid organism with one of its parents or with
an organism that is genetically similar to the parent. By repeating this
process, a certain characteristic or mutation can be isolated. Every backcross
you get rid of 50% of the non-relevant mutation.
Bacterial defence systems – ways in which bacteria protect themselves from
viral infection. Restriction modification means that endonucleases cut up
foreign DNA at specific recognition sites, while the own DNA is protected by
methyl groups to the sites. They can also use CRISPR-Cas to cut the viral DNA.
Finally, bacteria can also shed their cell wall in the presence of phages. Then
there will be no receptor proteins for the viruses to attach to.
Bacteriophages – a virus that infects and replicates within bacteria and
archaea. This includes two cycles. During the lytic cycle the viral DNA is
injected into the cytoplasm, replicated and new phages are formed. In the
lysogenic cycle the viral DNA is integrated in the host chromosome,
this is called a prophage, and replicated in that way. In this cycle there are no
viral proteins produced. There are three types of phages. Virulent phages
only have a lytic cycle. Temperate phages have a lytic and lysogeny cycle.
Cryptic phages only have the prophage phase. There is a trade-off between
lysis time and burst size.
Balanced lethal system – a situation where two different forms of a
chromosome hold unique, recessive, lethal alleles with functioning gene
copies on the alternate chromosome. Only heterozygotes are viable, leading to
a survival rate of 50%. This problem cannot be fixed by evolution, since
recombination is supressed. Recombination relies on homology between
chromosomes and in this case, there is no homology. Non-recombining
regions act as one single giant gene, called a supergene, and are often lethal
when homozygous.
Black queen hypothesis – describes the evolutionary strategy to lose costly
functions in favour of improving growth efficiency. This results in mutants
(cheaters) becoming obligately dependent upon a provider to produce a
necessary resource. This explains how natural selection can drive gene loss
(besides the reduction in energetic costs).
Chromosome conformation capture – a method that is used to analyse the
interactions and organization of chromatin in a cell. Can be useful for genome
assembly, since it also says something about the spatial organization of
chromosomes. Also called 3C. This, combined with next generation
sequencing is used to detect genome-wide chromatin interactions (it is called
Hi-C). It can also help investigate the organization of the genome and its role in
gene regulation, DNA replication and disease.

, Complementation group – mutations that occur in the same gene and thus
control the phenotype, from a complementation group. Each mutation in a
given complementation group is a mutant allele of the gene.
Conserved sequence – a base sequence in DNA (or an amino acid sequence in
a protein) that has remained essentially unchanged throughout evolution.
These sequences are usually required for basic cellular stability, function and
reproduction. In general prokaryotes have very little conserved sequences.
Eukaryotes on the other hand have a lot of conserved DNA (for example
intron positions).The gene order can also be conserved on chromosomes, this
is called synteny. Synteny offers a strong phylogenetic signal. So, it can
be used for comparative genomics and phylogenomics to study the evolutionary
histories of organisms based on whole genomes.
De novo – means that there is no reference. For example, de novo genome
assembly means that the obtained sequences are assembled without the
help of a reference sequence.
DNA – the genetic material that is present in organisms. Consists of sugar
(deoxyribose), a phosphate group and nitrogenous bases. There are
pyrimidines (C, T and U) and purines (A and G). The connection between A
and T has two hydrogen bonds, instead of three. Sugar, phosphate and the
nitrogenous base together is called a nucleotide. DNA can be coiled in
different ways. DNA can attach to a histone; eight histones can come
together and form a nucleosome. If the DNA is coiled very tightly it is
called heterochromatin and it cannot be transcribed. If it is less tightly
wound it is active and called euchromatin.
DNA replication – starts with topoisopolymerase which relaxes supercoiled
DNA, then helicase unwinds the DNA. DNA polymerase III can replicate
the DNA from 5’ to 3’ on the leading strand. On the lagging strand primase is
needed to make short primers and DNA polymerase III replicates small
pieces, DNA polymerase I fills the gaps that are left and ligase pastes
everything together.
Eukaryotes – organisms that have a cell nucleus and membrane-bound
organelles. They probably evolved from endosymbiosis (the cell engulfed a
bacterial cell which became an organelle). These organelles, mitochondria and
chloroplasts, have their own DNA. The eukaryotic genome is between 10 million
and 100.000 million bp. In eukaryotes one gene can lead to different
proteins, since mRNA can be altered in multiple ways through alternative
splicing. Exons (in humans about 1,5%) have the important information.
Repetitive elements in the DNA contribute to large introns. Introns of
developmental genes are usually shorter than those of non-developmental
genes.
Functional genomics – a field of study that aims to understand how genes lead
to phenotypes. It focusses on cellular information processing mechanisms. A
part of this study is transcriptomics, which focusses on gene expression
(splicing, etc). Another one is epigenetics, which revolves around the
regulation of gene expression. Epigenetics looks at how non-hereditary
changes to the genome regulate its activity. This includes methylation, DNA
folding but also environmental factors such as stress and diet. Three important
protocols for functional genomics are: ChIP-seq (chromatin
immunoprecipitation), ATAC- seq (assay for transposase-accessible chromatin)
and RNA-seq (transcriptome mRNA, for expression levels). RNA sequencing
gives the average gene expression from all cells. By doing a single-cell RNA-
seq it is possible to see the expression level of a specific cell and thus see
the variation between cell types.
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