This presentation contains basic information about the mouse being used as a model organism, its genome, how the genome of the mouse was sequenced and a comparison between mouse genome and human genome.
Scoring system is a set of values for qualifying the set of one residue being substituted by another in an alignment.
It is also known as substitution matrix.
Scoring matrix of nucleotide is relatively simple.
A positive value or a high score is given for a match & negative value or a low score is given for a mismatch.
Scoring matrices for amino acids are more complicated because scoring has to reflect the physicochemical properties of amino acid residues.
Cell cell hybridization or somatic cell hybridizationSubhradeep sarkar
What is Cell-Cell Hybridization?
History
More about Somatic cell Hybridization
Mapping of genes by somatic cell Hybridization
Hybridoma technology
Other Applications of Somatic Cell Hybridization
DNA SEQUENCING METHODS AND STRATEGIES FOR GENOME SEQUENCINGPuneet Kulyana
This presentation will give you a brief idea about the various DNA sequencing methods and various strategies used for genome sequencing and much more vital information related to gene expression and analysis
Introduction
Definition
History
Why are the transgenic animals being produced
Transgenic mice
Mice: as model organism
Methods of creation of transgenic mice
knock-out mice
Application of transgenic mice
Conclusion
References
A knockout mouse is a mouse in which a specific gene has been inactivated or“knocked out” by replacing it or disrupting it with an artificial piece of DNA.
The loss of gene activity often causes changes in a mouse's phenotype and thus provides valuable information on the function of the gene.
Scoring system is a set of values for qualifying the set of one residue being substituted by another in an alignment.
It is also known as substitution matrix.
Scoring matrix of nucleotide is relatively simple.
A positive value or a high score is given for a match & negative value or a low score is given for a mismatch.
Scoring matrices for amino acids are more complicated because scoring has to reflect the physicochemical properties of amino acid residues.
Cell cell hybridization or somatic cell hybridizationSubhradeep sarkar
What is Cell-Cell Hybridization?
History
More about Somatic cell Hybridization
Mapping of genes by somatic cell Hybridization
Hybridoma technology
Other Applications of Somatic Cell Hybridization
DNA SEQUENCING METHODS AND STRATEGIES FOR GENOME SEQUENCINGPuneet Kulyana
This presentation will give you a brief idea about the various DNA sequencing methods and various strategies used for genome sequencing and much more vital information related to gene expression and analysis
Introduction
Definition
History
Why are the transgenic animals being produced
Transgenic mice
Mice: as model organism
Methods of creation of transgenic mice
knock-out mice
Application of transgenic mice
Conclusion
References
A knockout mouse is a mouse in which a specific gene has been inactivated or“knocked out” by replacing it or disrupting it with an artificial piece of DNA.
The loss of gene activity often causes changes in a mouse's phenotype and thus provides valuable information on the function of the gene.
Introduction
Cre-lox recombination
Cre-lox system- Cre recombinase , loxP site
FLP-FRT recombination
FLP-FRT system- FLP recombinase , FRT site
Mechanism of Cre-lox and FLP-FRT recombination
Binding
Synapsis , cleavage and strand exchange
Three type of arrangement
Inversion
Translocation/ Insersion
Deletion
Application of Cre-lox and FLP-FRT recombination
Disadvantage of FLP-FRT
Advantage and disadvantage of Cre-lox
Conclusion
References
Global and local alignment (bioinformatics)Pritom Chaki
A general global alignment technique is the Needleman–Wunsch algorithm, which is based on dynamic programming. Local alignments are more useful for dissimilar sequences that are suspected to contain regions of similarity or similar sequence motifs within their larger sequence context.
The direct microinjection of DNA into the cytoplasm or nuclei of cultured cells is sometimes used as a transfection method. It is highly efficient at the level of individual cells. The most significant use of this technique is introduction of DNA into the oocytes, eggs and embryos of animals, either for transient expression analysis (e.g. in fish or Xenopus) or to generate transgenic animals (e.g. mice, Drosophilathis). The procedure is time consuming and only a small number of cells can be treated. Originally, this technique was used for the transformation of cells that were resistant to any other method of transfection. Stable transfection efficiencies are extremely high, in the order of 20%, and very small quantities of DNA are sufficient.
This technique provides direct nuclear delivery of DNA avoiding the endogenous pathway and also ensures that the DNA is delivered intact. Microinjection is suitable for the introduction of large vectors such as YACs into the pronuclei of fertilized mouse eggs. DNA delivered in this manner must be very pure so it needs a lot of preparation as it is necessary to avoid fragmentation. Shearing can also occur in the delivery needle, and large DNA fragments are often protected by suspension in a high salt buffer and/or mixing with polyamines and other protective agents. Now transfection of cultured cells is automated with computer-controlled micromanipulation and microinjection processes as well as the automated production of injection capillaries and the standardization of cell preparation procedure.
To modifying the structure of a specific gene.
Gene targeting vector introduced into the cell.
Vector modifies the normal chromosomal gene through homologous recombination.
Useful in treating some human genetic disorders – Hemophilia, Duchenne Muscular Dystrophy.
Treating human diseases by genetic approaches – Gene Therapy.
Gene Therapy – Replacing the defective gene by normal copy of the gene.
Expressed sequence tag/EST is a short partial sequence, typically 200-400 bp long, of a complimentary DNA/Cdna.
EST is a short sub-sequence of a cDNA sequence.
Used to identify gene transcripts, and are instrumental in gene discovery and in gene-sequence determination.
Approximately 74.2 million ESTs are available in public databases.
EST results from one-short sequencing of a cloned cDNA.
Low-quality fragments.
Length is approximately 500 to 800 nucleotides.
Introduction
Cre-lox recombination
Cre-lox system- Cre recombinase , loxP site
FLP-FRT recombination
FLP-FRT system- FLP recombinase , FRT site
Mechanism of Cre-lox and FLP-FRT recombination
Binding
Synapsis , cleavage and strand exchange
Three type of arrangement
Inversion
Translocation/ Insersion
Deletion
Application of Cre-lox and FLP-FRT recombination
Disadvantage of FLP-FRT
Advantage and disadvantage of Cre-lox
Conclusion
References
Global and local alignment (bioinformatics)Pritom Chaki
A general global alignment technique is the Needleman–Wunsch algorithm, which is based on dynamic programming. Local alignments are more useful for dissimilar sequences that are suspected to contain regions of similarity or similar sequence motifs within their larger sequence context.
The direct microinjection of DNA into the cytoplasm or nuclei of cultured cells is sometimes used as a transfection method. It is highly efficient at the level of individual cells. The most significant use of this technique is introduction of DNA into the oocytes, eggs and embryos of animals, either for transient expression analysis (e.g. in fish or Xenopus) or to generate transgenic animals (e.g. mice, Drosophilathis). The procedure is time consuming and only a small number of cells can be treated. Originally, this technique was used for the transformation of cells that were resistant to any other method of transfection. Stable transfection efficiencies are extremely high, in the order of 20%, and very small quantities of DNA are sufficient.
This technique provides direct nuclear delivery of DNA avoiding the endogenous pathway and also ensures that the DNA is delivered intact. Microinjection is suitable for the introduction of large vectors such as YACs into the pronuclei of fertilized mouse eggs. DNA delivered in this manner must be very pure so it needs a lot of preparation as it is necessary to avoid fragmentation. Shearing can also occur in the delivery needle, and large DNA fragments are often protected by suspension in a high salt buffer and/or mixing with polyamines and other protective agents. Now transfection of cultured cells is automated with computer-controlled micromanipulation and microinjection processes as well as the automated production of injection capillaries and the standardization of cell preparation procedure.
To modifying the structure of a specific gene.
Gene targeting vector introduced into the cell.
Vector modifies the normal chromosomal gene through homologous recombination.
Useful in treating some human genetic disorders – Hemophilia, Duchenne Muscular Dystrophy.
Treating human diseases by genetic approaches – Gene Therapy.
Gene Therapy – Replacing the defective gene by normal copy of the gene.
Expressed sequence tag/EST is a short partial sequence, typically 200-400 bp long, of a complimentary DNA/Cdna.
EST is a short sub-sequence of a cDNA sequence.
Used to identify gene transcripts, and are instrumental in gene discovery and in gene-sequence determination.
Approximately 74.2 million ESTs are available in public databases.
EST results from one-short sequencing of a cloned cDNA.
Low-quality fragments.
Length is approximately 500 to 800 nucleotides.
Genome: The entire chromosomal genetic material of an organism.
Sequencing a genome: Determining the identity and order of nucleotides in the genetic material – usually DNA, sometimes RNA, of an organism.
Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional
this is done by me and my team mates of Wayamba University Sri Lanka for our project.From now we decided to allow download this file.I would be greatful if you could send your comments..
And I'm willing to help you in similar works.I'm in final year of my degree(.BSc Biotechnology)..
pubudu_gokarella@yahoo.com
A complete set of chromosomes/genes inherited as a unit from one parent called genome. The entire genetic complement of a living organism.
The total amount of genetic information in the chromosomes of an organism, including its genes and DNA sequences. The genome of eukaryotes is made up of a single, haploid set of chromosomes that is contained in the nucleus of every cell and exists in two copies in the chromosomes of all cells except reproductive and red blood cells. The human genome is made up of about 35,000 genes.
Using Supercomputers and Supernetworks to Explore the Ocean of LifeLarry Smarr
07.06.07
Director's Colloquium
Los Alamos National Laboratory
Title: Using Supercomputers and Supernetworks to Explore the Ocean of Life
Los Alamos, NM
Metagenomics as a tool for biodiversity and healthAlberto Dávila
A talk on the applications of metagenomics for the study of biodiversity and health, presented during the inaugural symposium of the Peruvian Society of Biochemistry and Molecular Biology. Lima, March 2018
Adsorption is a reversible process which is shown by solids like activated charcoal, zeolite, silica clay, alumina etc.The solute present in the feed continuously interacts with the absorbent and gets adsorbed
Copyright infringement is the use of works protected by copyright law without permission, infringing certain exclusive rights granted to the copyright holder, such as the right to reproduce, distribute, display or perform the protected work, or to make derivative works.
Biorestoration deals with restoring or bringing back to an original or near original state using living micro-organisms. Nature has a built in check and balance system in everything it does. If there is too much or too little of something nature will use various life forms to try to re-establish a balance
Values of Modern society vs Traditional societyJasleen Rajpal
Man is a social animal and has been living in groups since the pre-historic times. With time, these groups have evolved to become organized and civilized societies and have adopted different norms, cultures and trends that distinguish them from the other societies. But the process of evolution did not stop and continues till date, leading to the formation of the modern society by putting the traditional society behind the scene.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
2. 1. They have similarity with humans in terms of anatomy, physiology
and genetics.
2. They are cost effective, because they are cheap and easy to look
after.
3. Adult mice multiply quickly. They can reproduce as often as three
weeks.
4. The time between a mouse being born and giving birth (generation
time) is short, usually around 10 weeks. This means several
generations can be observed at once.
5. The mouse has a short lifespan (one mouse year equals about 30
human years) which means scientists can easily measure the effects
of ageing.
3. Mus Musculus
Figure: Scientific classification Figure: Two day old pupFigure: One day old pups
FACTS:
1. Breeding onset occurs at 50 days of age for both males and females.
2. The average gestation period is 20 days.
3. The average little size is 10-12 during optimum production.
4. The young are called pups and weigh 0.5 to 1.5 grams at birth.
(https://en.wikipedia.org/wiki/House_mouse)
4. STRAINS:
There are over 3000 genetically defined strains, including:-
Inbred Mice:
Results from 20 consecutive generations of brother and sister mating.
eg: C57BL/6, BALB/c, C3H, FVB, 129, DBA, CBA etc.
Hybrid Mice:
These are F1 crosses between two different inbred strains.
Recombinant inbred Mice:
Results from 20 generations of brother and sister mating starting from F2.
Coisogenic strains:
They differ from each other only at one genes
Transgenic mice:
Carry foreign DNA.
Knockout Mice:
5. Mice have 19 autosomes (compared to 22 in humans), and
have the centromere at the end, rather than the middle of the
chromosome (acrocentric).
The order and arrangement of genes on the chromosomes is
not the same as in humans, although there is often local
conservation between the species
7. Origins of mouse genomics
The Human Genome Project (HGP) was launched in 1990, it
included the mouse as one of its five central model organisms, and
targeted the creation of genetic, physical and eventually sequence
maps of the mouse genome.
By 1996, a dense genetic map with nearly 6,600 highly
polymorphic SSLP markers ordered in a common cross had been
developed providing the standard tool for mouse genetics.
Physical maps of the mouse genome also proceeded apace,
using sequence-tagged sites (STS) together with radiation-hybrid
panelsand yeast artificial chromosome (YAC) libraries to construct
dense landmark maps.
In 2003 MGSC reported a draft sequence of mouse.
8. Mouse Genome Sequencing Consortium
The International Mouse Genome Sequencing Consortium
sequenced and analyzed more than 95 percent of the genetic
code of Mus musculus, which contains about 2.5 billion DNA
base pairs compared to 2.9 billion in the human genome.
The MGSC originally consisted of three large sequencing centres
• The Whitehead/Massachusetts Institute of Technology (MIT)
Center for Genome Research
• The Washington University Genome Sequencing Centre
• The Wellcome Trust Sanger Institute—together with an
international database, Ensembl, a joint project between the
European Bioinformatics Institute and the Sanger Institute.
9. Sequencing strategy
The ultimate aim was to produce a finished, richly annotated
sequence of the mouse genome to serve as a permanent
reference for mammalian biology.
The strategy has four components:
(1) production of a BAC-based physical map of the mouse genome
by fingerprinting and sequencing the ends of clones of a BAC
library;
(2) WGS (whole genome shotgun) sequencing to approximately
sevenfold coverage and assembly to generate an initial draft
genome sequence;
(3) Hierarchical shotgun sequencing of BAC clones covering the
mouse genome combined with the WGS data to create a hybrid
WGS-BAC assembly; and
(4) Production of a finished sequence by using the BAC clones as a
template for directed finishing.
10. Sequencing and Assembly
Female mice of the C57BL/6J strain was used for sequencing.
The genome assembly was based on a total of 41.4 million
sequence reads derived from both ends of inserts (paired-end
reads) of various clone types prepared from B6 female DNA.
The inserts ranged in size from 2 to 200 kb.
A total of 33.6 million reads passed extensive checks for quality
and source, of which 29.7 million were paired; that is, derived from
opposite ends of the same clone.
The assembled reads represent approximately 7.7-fold sequence
coverage of the euchromatic mouse genome.
11. Together, the clone inserts provide roughly 47-fold physical
coverage of the genome.
The assembly contains 224,713 sequence contigs, which are
connected by at least two read-pair links into supercontigs (or
scaffolds).
supercontigs (scaffolds) were aligned to possible chromosomal
locations in the proper order and orientation.
Supercontigs were localized largely by sequence alignments
with the extensively validated mouse genetic map with some
additional localization provided by the mouse radiation-hybrid
mapand the BAC map
15. Similarities and differences between the human and
mouse genomes.
The mouse genome is about 14% smaller than the human
genome (2.5 Gb compared with 2.9 Gb). The difference probably
reflects a higher rate of deletion in the mouse lineage.
Over 90% of the mouse and human genomes can be
partitioned into corresponding regions of conserved synteny,
reflecting segments in which the gene order in the most recent
common ancestor has been conserved in both species.
At the nucleotide level, approximately 40% of the human
genome can be aligned to the mouse genome. These sequences
seem to represent most of the orthologous sequences that
remain in both lineages from the common ancestor, with the rest
likely to have been deleted in one or both genomes.
16. The mouse and human genomes each seem to contain about
30,000 protein-coding genes. The proportion of mouse genes with
a single identifiable orthologue in the human genome seems to be
approximately 80%.
Mouse–human sequence comparisons allow an estimate of the
rate of protein evolution in mammals. Certain classes of secreted
proteins implicated in reproduction, host defence and immune
response seem to be under positive selection, which drives rapid
evolution.
Despite marked differences in the activity of transposable
elements between mouse and human, similar types of repeat
sequences have accumulated in the corresponding genomic
regions in both species. The correlation is stronger than can be
explained simply by local (G+C) content and points to additional
factors influencing how the genome is moulded by transposons..
17. By additional sequencing in other mouse strains, about 80,000
single nucleotide polymorphisms (SNPs) have been identified. The
distribution of SNPs reveals that genetic variation among mouse
strains occurs in large blocks.
Conservation of synteny between human and mouse
A typical 510-kb segment of mouse chromosome 12 that shares common
ancestry with a 600-kb section of human chromosome 14 is shown.
18. Segments and blocks >300 kb in size with conserved synteny in
human are superimposed on the mouse genome.
19. Dot plots of conserved syntenic segments in three human and three mouse
chromosomes.
20. (G+C) content
The overall distribution of local (G+C) content is significantly
different between the mouse and human genomes. Such
differences have been noted in biochemical studies
Mouse has a higher mean (G+C) content
than human (42% compared with 41%).
Mouse genome
Human genome
21. CpG islands
Computer program can be used that attempts to recognize CpG
islands on the basis of (G+C) and CpG content of arbitrary lengths
of sequence to the non-repetitive portions of human and mouse
genome sequences.
The mouse genome contains fewer CpG islands than the human
genome (about 15,500 compared with 27,000).
Repeats
The single most prevalent feature of mammalian genomes is
their repetitive sequences.
All mammals have four classes of transposable elements:
(1) The autonomous long interspersed nucleotide element (LINE)
(2) Short RNA-derived short interspersed nucleotide elements
(SINEs);
(3) Retrotransposons
(4) DNA transposons.
23. Evolution of the Mouse Genome – SNP Deserts and
Gene Deserts
The availability of a draft sequence of the mouse genome
immediately initiated a comprehensive genome-wide study of
sequence variation between mouse inbred strains.
The common lab inbred strains were derived from a limited
number of ancestral progeny.
These strains have been of enormous utility in analysing and
mapping the genetic loci determining a whole range of biological
and disease phenotypes.
The search for sequence variants (SNPs) between the inbred
strains has two potential applications.
1) Allows us to look back in time at the relationship between the
various inbred strains and assess their origins and divergence.
2) It enables us to identify regions of the genome that may
underlie the common phenotypic characteristics of groups of
inbred strains.
24. What am I
doing with
my life?
What are you
doing with my
life?
Editor's Notes
Mice are extremely useful for studying complex diseases, such as atherosclerosis and hypertension, as many of the genes responsible for these diseases are shared between mice and humans. Research in mice provides insights into the genetic risk factors for these diseases in the human population.
It is relatively easy to manipulate the mouse genome, for example, adding or removing a gene to better understand its role in the body. This provides a powerful tool for modelling specific diseases when a mutated gene is known to play a role in the disease.
Immunodeficient mice can also be used as hosts to grow both normal and diseased human tissue. This has been a useful tool in cancer and AIDS research.
Inbred strains are well-characterized, genetically
uniform mouse models that can be used for a wide
variety of human biological and disease research.
The haploid genome is about 3 billion base pairs long. (2818.97 Mb size)
Mice have 20 chromosomes in their haploid genome.
The current count of primary coding genes in lab mouse is 24,500.
They have a GC % of about 41.95%
N50 is defined as the sequence length of the shortest contig at 50% of the total genome length. For example, consider 9 contigs with the lengths 2,3,4,5,6,7,8,9,and 10; their sum is 54, half of the sum is 27, and the size of the genome also happens to be 54. 50% of this assembly would be 10 + 9 + 8 = 27 (half the length of the sequence). Thus the N50=8, which is the size of the contig which, along with the larger contigs, contain half of sequence of a particular genome. Note: When comparing N50 values from different assemblies, the assembly sizes must be the same size in order for N50 to be meaningful
A contig is the assembly of overlapping clones without a gap, i.e. the unbroken series of clones assembled using overlapping sequences.
The N50 is defined as the minimum contig length needed to cover 50% of the genome.
Example For an assembly fragmented into 4 contigs with lengths: 1, 2, 4, and 5 kb (total size = 12 kb), half of the genome length is covered by the two largest contigs, and hence N50=4kb is the minimum contig length required to cover 50 percent of the assembled genome sequence.
N10 is the minimum contig length to cover 10 percent of the genome.
N90 is the minimum contig length to cover 90 percent of the genome.
In fact, only about 300 genes are unique to either organism, which further supports the use of the mouse models for studying various diseases as well as testing novel treatments. The key differences lie in those areas of the genome governing immunity, detoxification, smell and sex, which makes sense considering where rodents usually live, how they find food and the number of offspring they can produce.
the Broad Institute has been generating a map of single-nucleotide polymorphisms (SNPs) among mouse strains. The initial set contains ~340,000 SNPs and has been used to characterize the haplotype structure of the laboratory mouse. The current goal is a dense haplotype map (20 kb resolution) of 48 mouse strains, as well as an in-depth characterization of variation within 15 mouse strains.
This mixed strategy was designed to exploit the simpler organizational aspects of WGS assemblies in the initial phase, while still culminating in the complete high-quality sequence afforded by clone-based maps.
the mouse and human genomes have each been shuffled by chromosomal rearrangements. The rate of these changes, however, is low enough that local gene order remains largely intact. It is thus possible to recognize syntenic (literally ‘same thread’) regions in the two species that have descended relatively intact from the common ancestor.
Human chromosome 20 corresponds entirely to a portion of mouse chromosome 2, with nearly perfect conservation of order along almost the entire length, disrupted only by a small central segment (Fig. 4a, d). Human chromosome 17 corresponds entirely to a portion of mouse chromosome 11, but extensive rearrangements have divided it into at least 16 segments (Fig. 4b, e). Other chromosomes, however, show evidence of much more extensive interchromosomal rearrangement than these cases
L1 seems to have remained highly active in mouse, whereas it has declined in the human lineage.
only a single SINE (Alu) was active in the human lineage, the mouse lineage has been exposed to four distinct SINEs (B1, B2, ID, B4). Each is thought to rely on L1 for retroposition, although none share sequence similarity, as is the rule for other LINE–SINE pairs
Only four lineage-specific DNA transposon families could be identified in mouse (the mariner element MMAR1, and the hAT elements URR1, RMER30 and RChar1), compared with 14 in the primate lineage.
Comparisons of sequence from inbred strains demonstrate that the level of sequence differences between any two inbred strains varies enormously between different regions of the genome [24–26]. In some regions, the frequency of SNPs is as high as 1 in 250 bp. Other regions are relatively devoid of sequence variants and the SNP frequency is as low as 1 in 20 kb – the so-called SNP deserts. It is assumed that these deserts represent ancestral regions shared by the founder mice that were used to estab-lish most inbred strains.
