GENOMICS I
Genome and genomic variation projects in many organisms have generated a wealth of data analyzable only by computer - based methods.
Genomes and genome projects:
HUMAN
Genomes Guide at NCBI - National Center for Biological Information
Ensembl- NCBI/Sanger
Human, Mouse and Rat Genome Browsers at UC Santa Cruz
NHGRI - National Human Genome Research Institute
Human Genome Project Information at Oak Ridge National Lab
MOUSEMouse Genome Resources at NCBI
NIH Mouse Initiative Web site
Mouse Genome Sequencing Consortium
Celera Genomics
Mouse Genome Informatics (MGI) at the Jackson Laboratory
.RAT
Rat Genome Browser at UC Santa Cruz and at Jackson Labs.
FUGU (Salt water) and TETRAODON (Fresh Water) Pufferfishes
Compact genomes due to near absence of repetitive sequences
Fugu Rubripes - 365 MB genome, many gene clusters conserved with mammals
BLASTable genome at DOE Joint Genome Institute
AMPHIOXUS (Lancelet) and STRONGYLOCENTRUS (Sea Urchin)
Amphioxus, Branchiostoma floridae, a simple cephalochordate vertebrate with a much simplified vertebrate genome (500 MB)
is valuable for studies on gene evolution
e.g. a single HOX gene cluster compared to 4 in mammals
BLASTable genome at Max Planck Institute, Berlin
CIONA (Ascidian, Sea Squirt)
Ciona Intestinalis - a primitive (uro)chordate, genome size 155MB.
Larval stage resembles a tadpole.
Has many genes orthologous to mammals, some to plants.
Also useful for gene evolution and function studies.
Draft genome described in Science 298: 2157 - 2167, 2002
Genome with BLAST capability at DOE Joint Genome Institute
D. MELANOGASTERBDGP - Berkeley Drosophila Genome Project
NCBI - Genome Biology Site
C. ELEGANSThe C. Elegans Genome Project at the Sanger Center, UK
MICROBIAL GENOMESTIGR - The Institute for Genome Research
ORGANELLE GENOMES
Mitochondrial and plastid genomes derived from eubacteria via symbiosis.
Endosymbionts have lost the bulk of their genomes and acquired many host - derived properties.
Recent review in Ancient Invasions: from endosymbionts to organelles. Science (2004) 304:253 - 7
GENERAL AND COMPENDIAThe Genome Atlas at the Denmark Technical University
Related Genome Databases at U.Oregon
Genomics - a Global Resource at PHRMA
NCGR - National Center for Genome Resources
Genome Mapping Links at Roslin Institute, Edinburgh, Scotland
GENOME MINING GUIDE:
Current Topics in Genome Analysis 2003 and 2005 Webvideo courses at NHGRI
PROBLEMS:1. For the Mus musculus cadherin 11 (Cdh11) gene, RefSeq accession number NM_009866.3:
a. What is the genomic location on the genetic and physical mouse chromosome maps and orientation of the gene? What are some neighboring genes? Is there a cluster of related genes?
b. What is the size of the genomic sequence ?
c. How many exons are there in the gene?
d. What kind of exon is exon 1? What characterisitic verifies it as a genuine exon?
e. What are the principal repeat elements?
f. Using the answer to part (a) and the Human-Mouse Homology Map find the chromosomal location of the human Cdh11 gene
g. How much homology is there between the mouse and human genes and proteins?
h. What are suggested functions of the Cdh11 gene product (e.g. at OMIM)
i. Is there significant homology between the 5' UTRs of the human, mouse and rat transcripts?
Genetic variation databases:
1. SNP databases:
dbSNP at NCBI
The mouse SNP database at Roche
PROBLEM 1:
What nonsynonymous SNPs have been recorded for the human Cdh11 gene?
(Hint: use EntrezSNP, LocusLink, Molecular Variation Database option (VAR) )
PROBLEM 2:
Identify the SNP in the coding sequence of the Nramp gene between the C57Bl/6 and A/J mouse strains.
Does the SNP result in a change in aminoacid sequence? In what part of the protein?
Do you predict that the change will cause a change in protein function?
2. Haplotype
The pattern of SNPs in a genomic region of an individual or animal strain.
Genomes appear to consist of long sequences of low interindividual variability (Haploblocks) separated by recombination hotspots.
Haplotype analysis is more powerful than single SNP analysis in identifying disease & susceptibility traits.
example: Haplotype Mapping and Sequence Analysis of the Mouse Nramp Gene predict Susceptibility to Infection with Intracellular Parasites. Genomics (1994) 23, 51-61
HapMap now under construction
RESOURCES:
"Studying Genetic Variation I and II" lectures in Current Topics in Genome Analysis 2003 and 2005 Webvideo courses at NHGRI
The international HapMap Consortium. A haplotype map of the human genome. Nature vol 437, pp1299-1320, 2005.