MOUSE GENOME PROJECT BIOINFORMATICS 407

1. MOUSE GENOME PROJECTBIOINFORMATICS 407 PRESENTED BY: Rabia butt bb-307-032 Mehwishjavedbb-307-008 Zill-e-huma bb-307-031 Umm-e-habiba bb-307-035 Anamkamalbb-307-016 Anamshabbirbb-307-041 Nazishabid bb-307-009 presented to: SIR FAIZ UL AMIN

2. “The ability to manipulate the mouse genome coupled with the availability of genome sequence make the mouse a unique research tool” GENOME PROJECT ? 2o Chromosome pairs 2.5 billion base pairs 30,000 genes

3. Comparative Genomics Analysis and comparison of genomes from different species. • Functional Genomics Conducted using model organisms. • Close Relation Of Mouse And Human Musmusculus(mouse) Homo sapien(human) 40 Chromosomes 46 Chromosomes 2.6 billion Base pairs 3.2 billion Base pairs 25,000 Gene numbers 25,000 Gene numbers

4. Knock Out Mouse Transgenic mice. Target specific genes. Determination of gene function. Testing new drugs and devising novel therapies. • History By the 1700s, many varieties of mice domesticated. Mice were used to test the new theories of inheritance. Mating programs established to create inbred strains. • HUMAN MOUSE GENOME HUMOLOGY Mouse and Human shared common ancestor. 99% genes are homologous. Homology between genes at numerous chromosomal positions.

5. Genetic mapping of the mouse: “Graphic representation of the arrangement of genes or DNA sequences on a chromosome” Haldane’s report in 1915led to genetic mapping in mouse. Genetic linkage map of the mouse, consisting entirely of genetic markers. Provide thousands of anchor points that could be used to tie clones or DNA sequences to specific locations in the mouse genome.

6. Background of Mouse as a Model Organism Over the past century: As mammalian model system for genetic research. It has genetic and physiological similarities to humans. If immunodeficient mice. Current researches: Mice prone to different diseases. Immunodeficient mice . Researchers produced a process known as chemical mutagenesis.

7. Recent decades researches Many technologies are produced: Transgenic mice. Knock out genes. Knock in genes. Some reproductive technologiesproduced as follows: Cryopreservation of embryos, In vitrofertilization Ovary transplantation.

8. The Jackson Laboratory It is national repository for mouse . Established in 1929. The famous "Black 6" or C57BL/6J mouse strain was developed in the early 1920s by The Jackson Laboratory. Recent researchers at The Jackson Laboratory Includes cancer, development and aging, immune system and blood disorders, neurological and sensory disorders, and metabolic diseases.

9. Listed below is a sampling of mouse models developed by The Jackson Laboratory: Down Syndrome Cystic Fibrosis Cancer Glaucoma Type 1 Diabetes Epilepsy Heart Disease Muscular Dystrophy Ovarian Tumors

10. Comparison of human & mouse genome The mouse genome has about 2.5 billion base pairs The human genome has about 2.9 billion base pairs

11. Synteny and conserved syntenty between the mouse and human genomes

12. Repeat sequences in mouse and human genome • Repeat sequences are mainly either active or inactive elements are called Transposons or Transposable elements that move around the genome. • Three different mechanisms for transposition: • Conservative transposition • Replicative transposition • Retrotransposition

14. There are two sorts of repeat sequence: Ancestral repeats Lineage specific repeats

15. Comparison of mouse and human coding genes 23,000 predicted genes and 200,000 exons. 22,000 predicted genes and 191,000 exons. Pseudogenes An error can occur during transcription. Unprocessed pseudogenes

16. Comparison of Mouse and Human gene sets 99% of mouse genes have homologues in man. 80% of mouse genes that have a match on the same syntenic region in man are also the best match for that human gene. The less than 1% mouse genes (118) with no homologues in humans do have homologues in other species.

17. Gene families A number of genes in the same families is different between mouse and human About 20% of mouse olfactory receptor homologues are pseudogenes 25 mouse-specific gene clusters were identified where multiple duplications had occurred to the ancestral gene. reproduction. host defense and immunity Two categories of gene family (Ly49 in mouse and KIR in human) are unrelated.

18. Mouse Genome Databases • Mouse Genome Database (MGD) • The Cancer Genome Anatomy Project • Mouse Genome Informatics (MGI) • Gene Expression Database (GXD) Project • Mouse Tumor Biology (MTB) Database Project

19. Transgenic organism • Whose genetic material has been altered. • First transgenic mice was created by Rudolf Jaenisch in 1974. • To study gene function & how and why a specific gene is "turned on" in some tissues and "turned off" in others. Production of Transgenic Animals: Randomly Inserted Transgenes: • microinjection of DNA into the pronucleus of zygotes Targeted Gene Mutations: • injection of embryonic stem cells into blastocysts. • Complete microinjection set-containing of a microscope, micromanipulators, microinjectors and micropipettes.

21. Mario R. Capecchi, Ph.D., of the University of Utah, has won the 2007 Nobel Prize in Physiology or Medicine. work on "knockout mouse" technology, To "knockout" the OhNo gene, replace it with a mutated copy that doesn't work. Here's how:

24. Genome Sequence a Physical Map of the Mouse Genome: A 17-month project culminates in a physical map of the mouse using 300,000 BACs. 305,768 clones present in the physical map, 289,506 of which are contained within the 7,582 contigs. first breaking the genome into 150,000 base pair pieces called BACs, assembling Shotgun sequencing: long stretch of DNA is physically broken into small, approximately 2,000 base-pair. Craig Venter developed the technique in 1996. The NIEHS, National Academy of Sciences Institute of Laboratory Animal Resources (ILAR), and Oak Ridge National Laboratory Human Genome Group have combined efforts to establish a database that catalogs information on transgenic animals.

25. Ethical consideration • The genetic modification or cloning of companion animals. • Experiments intended to reduce the sentience of any species are not allowed. • A presumption against the genetic modification and cloning animals should only be allowed if it will contribute to the relief of serious human sufferings. • the applicant wishing to undertake genetic modification of animals to demonstrate that other approaches could not achieve broadly similar goals.

26. Advantages: • First, it is among the smallest mammals known with adult weights in the range of 25-40 g, 2,000-3,000-fold lighter than the average human adult. • Second, it has a short generation time — on the order of 10 weeks from being born to giving birth. • Third, females breed prolifically in the lab with an average of 5-10 pups per litter. • Fourth, an often forgotten advantage is the fact that fathers do not harm their young, and thus breeding pairs can be maintained together after litters are born. • most laboratory-bred strains are relatively docile and easy to handle

27. Disadvantages: Most significant differences between mice and humans are not in the number of genes but in the structure of genes and the activities of protein products. Single nucleotide differences can alter protein function and causes tissue malfunction. Changes have been linked to hereditary differences in height, brain development, facial structure, pigmentation. Due to changes, hands can develop structures that look like toes instead of fingers, and a mouse's tail can disappear completely.

28. Disorders to detect, model and treat Cystic fibrosis (CF) is the most common severe single gene disorder. Sufferers usually die in their mid twenties. But CF mice generally die perinatally from severe intestinal obstruction . Several transgenic mouse models have been created by insertional mutation and display similar molecular changes to CF patients. But the disease progress is extremely different. Serious lung disease is the cause of death in 95% of human patients but CF mice develop lung disease infrequently and mildly

29. LeschNyhan Syndrome is another single gene disorder, characterized by mental retardation and distressing behavioural abnormalities. Several mouse models were created with the same genetic defect but the mice did not display abnormal behaviour.

30. THANKS