Lecture 16 Genome Content

Question 1

Structural genomics:

Answer 1

organization and sequence of genetic information contained within a genome

Question 2

What is a genetic map?

Answer 2

locates genes or markers based on genetic recombination frequencies

Question 3

What is a physical map?

Answer 3

locates genes or markers based on the physical length of DNA sequence

Question 4

What are the limitations to genetic mapping?

Answer 4

Recombination frequencies vary from one region of the chromosome to another so it is approximate.
Also has lower resolution bc recombination is difficult to observe between loci that are very close to each other

Question 5

What map has greater accuracy and resolution?

Answer 5

Physical maps based on DNA sequences or restriction maps, accurate down to a single base pair of DNA sequence

Question 6

What was the 1st step in mapping the human genome?

Answer 6

detailed physical and genetic maps

Question 7

Define contig

Answer 7

A set of overlapping fragments that form a continuous stretch of DNA

Question 8

What are some of the ethical concerns arising out of the information produced by the Human Genome Project?

Answer 8

Privacy of a person’s genetic info and how such info will be used
Info used to discriminate against individuals with polymorphisms
Denied health insurace, limit opportunity for career etc
Genetic Information Nondiscrimination Act

“designer” babies, select embryos with desirable traits

Given that genes interact with each other and environment, and complex interaction lead to incomplete penetrance and expressivity, will ppl receive adequate counseling to properly interpret their genetic profiles?

Question 9

What is a single-nucleotide polymorphism?

Answer 9

SNPs are single base-pair differences in the sequence of a particular region of DNA from one
individual compared to another of the same species or population.

Question 10

How are SNPs used in genomic studies?

Answer 10

SNPs are useful as molecular
markers for mapping and pedigree analysis and may themselves be associated with phenotypic
differences.

Question 11

What is a haplotype?

Answer 11

A haplotype is a particular set of neighboring SNPs or other DNA polymorphisms observed on a single chromosome or chromosome region

Question 12

How do different haplotypes arise?

Answer 12

They tend to be inherited together as a set because of
linkage. Meiotic recombination within the chromosomal region can split the haplotype and create new recombinant haplotypes.

Question 13

What is linkage disequilibrium?

Answer 13

Linkage disequilibrium is the association of certain genetic variants (alleles) with each other via linkage on the same chromosome, so that these allelic combinations occur more frequently in the population than expected based on random assortment.

Question 14

How does it result in haplotypes?

Answer 14

The particular combinations of alleles at different loci within a region of the chromosome are called haplotypes. Distinct haplotypes occur because modern human populations have not undergone enough recombination to thoroughly shuffle the allelic combinations.

Question 15

What is copy-number variations?

Answer 15

The number of copies of DNA sequences varies from person to person
Copy number variation is the occurrence of more or less than the usual diploid copy number for a DNA sequence of longer than 1000 bp.
Most contain multiple genes and potentially affect the phenotype
ex. autism

Question 16

How do copy-number variations arise?

Answer 16

Such copy number variations could arise through deletion or

duplication of a segment of chromosomal DNA.

Question 17

What are expressed-sequence tags?

Answer 17

ESTs
Markers associated with DNA sequences that are expressed as RNA
(reverse transcription to produce a set of cDNA fragments

Question 18

Bioinformatics =

Answer 18

molecular biology + computer science

Question 19

Ab initio approach:

Answer 19

Scans sequence looking for features usually found within a gene

Question 20

Comparative approach:

Answer 20

Looks for similarity between a new sequence and sequences of known genes

Question 21

The ab initio approach finds genes by looking for:

Answer 21

common sequences found in most genes

Question 22

Computer algorithms (and humans) recognize or predict genes within genomic sequences by analysis of the following:

Answer 22

1. the presence of matching cDNA or EST sequences in a database
2. Open reading frames
3. Sequences characteristic of promoters upstream of a start codon of an open reading frame
4. Homology (sequence similarity) to previously characterized genes in the same or other species

Question 23

Metagenomics

Answer 23

Sequencing genomes of entire communities of organisms

Question 24

Synthetic biology

Answer 24

the creation from scratch novel organisms

Question 25

Functional genomics

Answer 25

characterizes what the sequences do - the Encode project

Question 26

Transcriptome:

Answer 26

all the RNA molecules transcribe from a genome

Question 27

Proteome:

Answer 27

All the proteins encoded by the genome

Question 28

Homologous sequences:

Answer 28

Genes that are evolutionarily related, derived from a common ancestor

Question 29

Orthologs:

Answer 29

Homologous genes in different species that evolved from the same gene in a common ancestor

Question 30

Paralogs:

Answer 30

Homologous genes arising by duplication of a single gene in the same organism

Question 31

What is the difference between orthologs and paralogs?

Answer 31

Orthologs are in different organisms; paralongs are in the same organism

Question 32

Describe how homology and sequence similarity is used to infer the function of a gene

Answer 32

For protein-coding genes, the DNA sequence is translated
conceptually into the amino acid sequence of the protein. The amino acid sequence of the protein then may yield clues to its function if it is similar to another protein of known function. For example, it is quite easy to recognize histones because their amino acid sequences are highly conserved among
eukaryotes. Even if the whole protein is not similar, it may have regions, or domains, that are similar to other domains with known functions or properties. Finally, the amino acid sequence may contain
small motifs or signatures that are characteristic of proteins with certain enzymatic activities or properties or subcellular localizations.

Question 33

Describe how phylogentic profile is used to infer the function of a gene

Answer 33

The coordinated absence or presence of clusters of genes in various species
implies that the genes in the cluster have related functions. For example, genes required for nitrogen fixation would all be present in nitrogen-fixing species but absent in other species.

Question 34

Describe how gene fusions are used to infer the function of a gene

Answer 34

In some species, genes of related function have undergone a fusion event to form a single multifunctional polyprotein. Then similar but separate component genes in other species can be presumed to have similar functions.

Question 35

Describe how gene clusters or operons are used to infer the function of a gene

Answer 35

In bacteria, genes in metabolic or functional pathways are often clustered together into an operon. Therefore, all the genes that are co-transcribed into a single polycistronic mRNA should have related functions.

Question 36

What is microarray?

Answer 36

A microarray consists of thousands of DNA fragments spotted onto glass slides in an ordered grid
(gene chips) or even proteins or peptides arrayed onto glass slides (protein chips). The identity of the
DNA or peptide at each location is known.

Question 37

How is microarray used to obtain info about gene function?

Answer 37

Gene chips are typically used in hybridization
experiments with labeled mRNAs or cDNAs to survey the levels of transcript accumulation for
thousands of genes, or even whole genomes, at one time. Peptide or protein chips can be used to identify protein-protein interactions or enzymatic activities or other properties of proteins.

Question 38

Reporter sequences:

Answer 38

Encoding an easily observed product used to track the expression of a gene of interest

Used with colored product, or antibody, or the reporter itself may be fluorescent

Question 39

How is mutagenesis screen carried out?

Answer 39

After random mutagenesis with chemicals or transposons, the mutant progeny are screened for phenotypes of interest. The mutant gene can be identified by cosegregation with molecular markers
or by sequencing the position of transposon insertion. To verify that the mutation identified is truly responsible for the phenotype, the same mutation can be introduced into a wild-type copy of the gene
via site-directed mutagenesis and the phenotype observed in the offspring.

Question 40

DNA content varies considerably among different multicellular organisms. Is this variation
closely related to the number of genes and the complexity of the organism? If not, what accounts for
some of these differences?

Answer 40

The “complexity” of an organism is not well-defined and thus difficult to quantify. DNA content can vary widely among related species, so there appears to be little relation between the “complexity” of an organism, the number of genes, and the DNA content. Large differences in DNA content may arise from differences in the frequency and size of introns, the abundance of DNA derived from transposable elements, and duplication of the whole or substantial parts of the genome in the evolutionary history of the species.

Question 41

Colinearity:

Answer 41

Presence of many genes in the same order in related genomes due to evolution for an common ancestral genome

Question 42

Segmental duplication:

Answer 42

A duplication involving a relatively large (greater than 1000 bp) stretch of chromosomal DNA
sequence.

Question 43

The human genome does not encode substantially more protein domains than do invertebrate
genomes, yet it encodes many more proteins. How are more proteins encoded when the number of
domains does not differ substantially?

Answer 43

The human genome contains proteins with many more combinations of domains, often featuring
multiple domains on a single protein.

Question 44

What is comparative genomics?

Answer 44

Comparative genomics analyzes the similarities and differences among genomes to achieve insights into genomic or organismal evolution or relationships between groups of genes and physiological
functions.

Question 45

How does proteomics differ from genomics?

Answer 45

Whereas genomics is the analysis of whole genome DNA sequences and their organization,
expression, and function, proteomics focuses on the complete set of proteins made by an organism

proteome varies within a species from cell
type to cell type, with stage of development, and with time in response to signals and other environmental stimuli. Proteins also undergo numerous modifications that affect protein localization
and function.