CHAPTER 15 Genomics and Proteomics

Structural genomics

the study of the organization and sequence of the genetic information contained within a genome, providing the basic DNA sequence information that is used in functional and evolutionary studies

Genomics

the field of genetics that attempts to understand the content, organization, function, and evolution of the genetic information contained in whole genomes

Genetic Maps (aka linkage maps)

provide a rough approximation of the locations of genes relative to the locations of other known genes. These maps are based on the genetic process of recombination (hence the name genetic map).

Physical Maps

based on the direct analysis of DNA, and they place genes in relation to distances measured in number of base pairs, kilobases, or megabases

• Physical maps generally have higher resolution and are more accurate than genetic maps.

The main obstacle to sequencing a whole genome is

the immense size of most genomes.

• sequencing cannot begin at one end of a chromosome and continue straight through to the other end; only small fragments of DNA— typically 500 to 700 nucleotides—are usually sequenced at one time. Therefore, determining the sequence for an entire genome requires that the DNA be broken into thousands or millions of small overlapping fragments that can then be sequenced.

Map-Based Sequencing

short sequenced fragments are assembled into a whole-genome sequence by first creating detailed genetic and physical maps of the genome, which provide known locations of genetic markers (restriction sites, genes, or known DNA sequences) at regularly spaced intervals along each chromosome. These markers are later used to help align the short, sequenced fragments in their correct order.

Whole-Genome Shotgun Sequencing

Method of sequencing a genome in which sequenced fragments are assembled into the correct sequence in contigs by using the overlaps in sequence.

The requirement for overlap in Whole-Genome Shotgun Sequencing means

most of the genome must be sequenced many times

sequencing coverage

The average number of times a nucleotide in the genome is sequenced

Single-Nucleotide Polymorphisms

A site in the genome where individual members of a species differ in a single base pair.

To be considered an SNP, a variant must

reach a frequency of at least 1% in a population; thus, very rare variations are not usually considered SNPs

Haplotype

A specific set of linked genetic variants or alleles on a single chromosome or on part of a chromosome.

Single-nucleotide polymorphisms within a haplotype are physically linked and therefore

tend to be inherited together.

New haplotypes can arise through

mutation or crossing over, which wbreaks up the particular set of SNPs in a haplotype.

Genome-Wide Association Studies

Looks for nonrandom associations between the presence of a trait and alleles at many different loci scattered across a genome—that is, for associations between traits and particular suites of alleles in a population.

Bioinformatics

Interdisciplinary field that combines molecular biology and computer science; develops databases, computer-search algorithms, gene-prediction so ware, and other analytical tools that are used to make sense of DNA-, RNA-, and protein-sequence data.

Results and Implications of the Human Genome Project

The human genome sequence was declared completed in the spring of 2003, although some gaps still remain. For most chromosomes, the finished sequence is 99.999% accurate, with less than one base-pair error per 100,000 bp, an accuracy rate 10 times that of the initial goal.

Metagenomics

A field of genetics in which the genome sequences of an entire group of organisms that inhabit a common environment are sampled and determined.

Microbiome

Complete set of all bacteria found in a particular environment; for example, the human microbiome consists of all bacteria found in and on the human body.

Synthetic Biology

A field that seeks to design organisms that might provide functions useful to humanity.

functional genomics

Area of genomics that studies the functions of the genetic information contained within genomes.

Transcriptome

Set of all RNA molecules transcribed from a genome.

Proteome

Set of all proteins found in a cell.

homologous genes

Evolutionarily related genes descended from a gene in a common ancestor

Microarray

Ordered array of known DNA fragments, fixed to a solid support in an orderly pattern, which serve as probes to detect the presence of complementary sequences; often used to assess the expression of genes in various tissues and under different conditions.

• can be used to examine gene expression associated with disease progression

To visualize the results, the scan of microarrays is often converted to a

heat map

Heat map

A visual (color) representation of a continuous variable, like the expression of a gene.

RNA Sequencing

determines the presence of RNA molecules in a cell by sequencing cDNAs copied from cellular RNA molecules providing detailed information about gene expression, including the types and number of RNA molecules produced by transcription and the presence of alternatively processed RNA.

• carried out by isolation of RNA molecules from cells, conversion of the RNA to complementary DNA (cDNA), and sequencing of the cDNAs.

proteome

the complete set of proteins found in a given cell.

Proteomics:

The study of the proteome

Human Proteome Project

Plans underway to identify and characterize all proteins in the human body

mass spectrometry

a method for precisely determining the molecular mass of a molecule

• a molecule is ionized and its migration rate in an electrical field is determined. Because small molecules migrate more rapidly than do larger molecules, the migration rate can accurately determine the mass of the molecule.