What is meant by the term genomics?
The study of genome
What are the three subcategories of genomics? What is the goal of each?
1) Structural: the sequence of nucleotides that make up the genome of species
2) Functional : identifies function of a portion of the genomes, like protein and enzymes
3) Comparative: look at similarities and differences in genomes of different species
What type of genomics was used as the first step in deciphering the human genome?
What was the goal of this first step in structural?
Identification of genes and important sequences (determine gene sequences that make up the bases of that genome)
What are the two types of sequencing methods?
Clone by clone (a.k.a. map base cloning) and whole- genome shotgun
Which was sequencing method was developed first?
clone by clone
Which was used to develop the foundation for the human genome?
clone by clone
Which is more simple, more efficient and less time-consuming?
whole genome shotgun
What is a contig?
Contiguous sequences or fragments of DNA that are spliced together to make a long sequences
What type of molecule is used in clone-by-clone sequencing?
What are the components of the molecule?
Components of Fragments of human DNA + cloning vector
What is the order of events in clone-by-clone sequencing?
1) Individual chromosomes are isolated and cut into many pieces using multiple restriction enzymes leading to digestion
2) Fragments from digestion with restriction enzymes are cloned or inserted into YACs or BACs
3) Fragments stored in artificial chromosomes lead to artificial/chromosome library
4) When ready to sequence, use restriction enzyme to cut restriction fragments out of YAC/BAC
5) Fragment cloned or inserted into cosmid-specialized structure that makes copies of the fragments
6) Sections of the fragment CA.4KBLONG inserted into plasmid of sequencing vector leads to sequenced in the lab
7) After the sequences of the 4KB fragments are identified, they are then compared to the sequences of other small fragments from the same chromosomes
8) Look for overlapping sequences at end of fragments. Contigs- contiguous fragments
9) Overlapping sections of contigs then used to align the sequences from different fragments
10) Find enough overlapping sequences and that leads you to determine the sequence of the whole chromosome
What is a chromosome library?
Fragments of DNA stored in artificial chromosomes
Which sequencing method utilizes chromosome libraries?
clone by clone
What steps are similar in clone-by-clone sequencing and shotgun sequencing?
Both start by isolating a single chromosome and end with sequencing restriction fragments then aligning contigs
Which sequencing method uses direct sequencing of restriction fragments?
How are contigs aligned?
Fragments with overlapping identical sequences are aligned
What is bioinformatics?
Computer based approach to organize, share and analyze data
What types of information can be determined using bioinformatics?
Determines gene structure by aligning the contigs.. identifying gene sequence and expression and identifying regulatory regions .. like promoters and terminators ... and analyze protein structure and function to predict amino acid sequene
What is GenBank?
Data base with sequenced data from more than a hundred gazillion species
What is the source of the information in GenBank?
Researchers around the world submit data to the GenBank
What is a homology search?
GenBank search for identifying sequences similar to a newly found sequence
What does the acronym BLAST stand for?
Basic Local Alignment Search Tool
When is BLAST used?
To conduct a homology search in Gen Bank
You have just sequenced part of the genome of a mouse and you perform BLAST. You find that your sequence is 94% similar to the sequence for fur color in rat, 75% similar to the sequence for eye color in rat, 42% similar to the sequence for tail length in vole and 82% similar to the sequence for coat length in hamster. Based on these results, what trait is probably controlled by your sequence in mouse?
If your sequence does not have a good match in GenBank, what can you look for to determine whether your sequence codes for a gene?
Sequences of known regulatory region (look for wat you know)
What was the goal of the Human Genome Project?
to sequence and identify all genes in human genome
How many nucleotides are in the human genome?
What percent of sequences in human genome are protein-coding?
How many genes do these sequences represent?
20-25 thousand genes
How many proteins are produced by these genes?
200, 000 proteins
What percent of the genome is similar in all individuals?
What percent of genes have no known function?
Why do we suspect these are genes even though we don't know what they do?
They have regulatory regions like promoters and terminator associated w/ genes but just don't know what they do
The function of about 60% of human genes has been determined; what three methods were used to identify their function?
1) Homology searches
What is the function of the most common group of genes in the human genome?
Nucleic acid metabolism - 7.5% of all genes with known function
characteristics are common to the genomes of eukaryotes (higher organisms)?
They have a lower gene density versus prokaryote type
How do they differ from prokaryotes?
Have introns and prokaryotes don't and have repeat sequences that account for a large portion of the genome
Is gene density constant within the genome of a species?
No- varies within genome of the species
How does the gene density of human chromosome #22 compare to the gene density of chromosome 13?
Human C22 = 1 gene/64KB (chromosome 22 = 1 gene .... )C13 = 1 gene/155KB
What percent of the human genome is composed of repeated sequences?
How about the corn genome?
Why do higher organisms need large genomes even though a small percent of their genomes are protein-coding?
Low gene density, introns and repeats all need larger genome to accommodate all information needed to live
How does the dog genome compare in size to the human genome?
2.5 billion bases and human have 3
What percent of our genes are shared with dogs?
What genetic disorders are common among dogs and humans?
Turner Kleinfelter (sex chromosome aneuploidy), genetic predisposition to heart disease, cancer and deafness
Is most genetic variation in dogs within breeds or among breeds?
btwn or among breeds
• A SNP for what gene was found to be present in small dog breeds and absent in large breeds?
SNP in IGF1 (insulin-like growth factor gene) - presents in all small breeds and absent in large breeds
What is the function of this gene?
Why is this important in relation to humans?
Same gene in humans ; important role in producing growth hormones responsible for muscle and growing bones during adolescents
Because similar in function in same gene - mutation in IGF1 gene influences growth development in size and dogs and humans- homologous gene, similar in function
What five other fields of -omics did we discuss? What is the goal of each field?
Metabolomic - identify protein or enzyme pathways that play a role in cell metabolism
Proteomics - analysis of all proteins present in cell or all tissue
Transcriptiomics - study of all expressed genes in particular cell or tissue
Methyalomics- examines how methylation regulates gene expression
Metagenomics - study genomes of organisms collected from a particular environment (a.k.a.
What is cancer?
Loss of cell cyle control during mitosis
How do tumors arise?
Genetic change or mutation in single cell leading to uncontrolled cell proliferation leading to clonal tumors
How similar are the cells in a single tumor?
all cells are genetically identical to one another in a single tumor
What is the difference between benign and malignant or cancerous tumors?
Benign tumors don't invade or spread to surrounding tissues; malignant or cancerous invade
What is the difference between sporadic and familial or inherited cancers?
Sporadic from mutation in somatic cells and are not transmitted to offspring
Familial are inherited and can be transmitted to the offspring
What four lines of evidence suggest that cancer is a genetic disease?
Chromosomal abnormalities common in cancer - multiple rearrangements and duplication of entire chromosome
2. Transmitted by traits - some cancers are heritable (some cancers are transmitted like traits, meaning some cancers are heritable)
3. Many carcinogens (substances identified as cancer causing also called mutagens) causing changes in genetic material-Mutagens - cause changes to genetic material
4. Individuals w/ mutations in DNA repair system have increased risk for cancer because they accumulate mutations