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What is the primary function of DNA microarrays?
What is the advantage of using DNA microarrays over traditional methods?
What is the purpose of the DNA sequences on a microarray?
How are the DNA fragments on a microarray typically prepared?
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What is the purpose of a single slide on a DNA microarray?
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What is the technology used to make DNA microarrays similar to?
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What is an application of DNA microarrays?
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What is the result of using a DNA microarray as a hybridization tool?
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What is the primary goal of functional genomics in a given species?
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What is the term used to describe the entire collection of proteins that an organism can make?
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What is the primary focus of epigenomics?
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What is the term used to describe the large-scale study of small molecules within cells, biofluids, tissues or organisms?
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What is the primary focus of bioinformatics?
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What is the term used to describe the analysis of the complete set of gene expression?
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What is the term used to describe the sum of constituents within a cell at all levels?
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What is the primary goal of proteomics?
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What is the primary purpose of functional microarrays?
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What is the term for the marriage between genetics and biocomputing?
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What are the three basic components of computer analysis of genetic sequences?
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What is the primary function of a computer program in bioinformatics?
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What is the purpose of generating a computer data file?
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How are genetic sequences typically entered into a computer file?
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What is one of the ways genetic sequences can be analyzed?
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What is the term for the study of the evolutionary relationship between genetic sequences?
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What is the primary goal of gene prediction?
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What strategy do computer programs use to locate genes by searching for specific signals?
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What is the primary difference between search by signal and search by content strategies?
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What is an open reading frame (ORF)?
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Why are there six possible reading frames in a newly discovered sequence?
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What is the significance of homologous genes?
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What is the purpose of translating a genomic DNA sequence in all three reading frames?
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Why are long ORFs contained within chromosomal gene sequences in prokaryotes?
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What is the primary goal of using a tool like BLAST?
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What does a small E-value in BLAST indicate?
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Why is homology among protein sequences easier to identify than is DNA sequence homology?
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What is the purpose of the E-value in BLAST?
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What is the result of using a query sequence in BLAST?
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Why are the results of a BLAST search typically sorted by E-value?
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What is the advantage of using BLAST over other sequence comparison methods?
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What is the primary input for a BLAST search?
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What is the purpose of multiple sequence alignment?
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What is the characteristic of conserved sites in homologs?
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How many paralogs of the globin gene family are functionally expressed in humans?
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What is the composition of hemoglobin protein?
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During what stage of development are the ζ and ε genes expressed?
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What can be inferred from the high degree of sequence similarity between species?
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Who originally proposed the multiple sequence alignment approach?
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What is the result of comparing the sequences of the hemoglobin chains?
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What is the category of the β gene in the globin gene family?
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What is the purpose of multiple sequence alignment in the globin gene family?
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Study Notes
Omics
- In biology, the word "omics" refers to the sum of constituents within a cell at all levels.
- There are several types of omics, including:
- Epigenomics: deals with chemicals that can tell the genome what to do
- Proteomics: studies the entire collection of proteins that an organism can make
- Bioinformatics: analyzes biological information using a mathematical/computational approach
- Transcriptomics: analyzes the complete set of gene expression
- Metabolomics: is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms
Functional Genomics
- The goal of functional genomics is to elucidate the roles of genetic sequences in a given species.
- It aims to understand gene function and the interplay among many different genes.
- Recent genome-sequencing projects have enabled the study of gene function at a more complex level.
- We can now examine groups of many genes simultaneously.
DNA Microarrays
- DNA microarrays (also called gene chips) are a technology that makes it possible to monitor thousands of genes simultaneously.
- A DNA microarray is a small silica, glass, or plastic slide that is dotted with many sequences of DNA.
- Each of these sequences corresponds to a known gene.
- The DNA fragments on a microarray can be either amplified by PCR and then spotted onto the microarray or synthesized directly on the microarray itself.
- A single slide contains tens of thousands of different spots in an area the size of a postage stamp.
- The technology for making DNA microarrays is quite amazing, involving spotting technologies that are quite similar to the way that an inkjet printer works.
Applications of DNA Microarrays
- DNA microarrays can be used to:
- Compare microarray data using cDNAs derived from RNA of different cell types to identify genes that are expressed in a cell-specific manner.
- Identify genes that are expressed in a cell-specific manner.
- Probe the function of proteins.
Bioinformatics
- The computer has become an important tool in genetic studies.
- The marriage between genetics and biocomputing has yielded an important branch of science: bioinformatics.
- Computer analysis of genetic sequences usually relies on three basic components: a computer, a computer program, and some type of data.
- A computer program is a defined series of operations that can analyze data in a desired way.
- A first step in the computer analysis of genetic data is the generation of a computer data file.
- The genetic sequence can be analyzed in many ways, including:
- Does a sequence contain a gene?
- Where are functional sequences, such as promoters and splice sites?
- Does a sequence encode a polypeptide?
- Is a sequence homologous to other sequences?
- What is the evolutionary relationship between two or more genetic sequences?
Approaches to Identify Genes
- Gene prediction refers to the process of identifying regions of genomic DNA that encode genes.
- Computer programs can employ different strategies to locate genes, including:
- Search by signal: looking for an organization of known sequence elements that are normally found within a gene.
- Search by content: looking for sequences that differ significantly from a random distribution due to codon bias within protein-encoding genes.
Open Reading Frames
- Another way to locate coding regions within a DNA sequence is to examine reading frames.
- In a DNA sequence, the reading of codons could begin with the first, second, or third nucleotide.
- These are called reading frame 1, 2, and 3, respectively.
- An open reading frame (ORF) is a nucleotide sequence that does not contain any stop codons.
- In prokaryotes, long ORFs are contained within the chromosomal gene sequences.
- In eukaryotes, however, the chromosomal coding sequences may be interrupted by introns.
Homologous Genes
- When comparing genetic sequences, researchers sometimes find two or more similar sequences.
- Homology between genetic sequences can be identified by computer programs and databases.
- A strong correlation is typically found between homology and function.
- Homologous genes are derived from the same ancestral gene.
BLAST
- BLAST (Basic Local Alignment Search Tool) is a program that starts with a genetic sequence and then locates homologous sequences in a large database.
- Homology among protein sequences is easier to identify than is DNA sequence homology.
- The relationship between the query sequence and each matching sequence is given an E-value (Expect value).
- The E-value represents the number of times that the match or a better one would be expected to occur purely by random chance in the entire database.
Proteomics
- Proteomics is the study of the functional roles of proteins in a species.
- The entire collection of proteins in a species is known as the proteome.
- Genomic data can provide insights into the proteome, but may not accurately measure protein abundance.
The Proteome is Larger than the Genome
- The proteome is larger than the genome due to cellular processes such as:
- Alternative splicing
- RNA editing
- Post-translational covalent modification
Alterations that Affect the Proteome
- Alternative splicing:
- Occurs in eukaryotes
- A single pre-mRNA is spliced into multiple versions
- Splicing is often cell-specific or related to environmental conditions
- RNA editing:
- Less common than alternative splicing
- Leads to changes in the coding sequence of mRNA after it is made
DNA Microarrays
- A DNA microarray is a technology that allows for the simultaneous monitoring of thousands of genes.
- It consists of a small silica, glass, or plastic slide dotted with many DNA sequences, each corresponding to a known gene.
- The DNA fragments on the microarray can be:
- Amplified by PCR and then spotted onto the microarray
- Synthesized directly on the microarray
- A single slide can contain tens of thousands of different spots, with the relative location of each spot known.
Applications of DNA Microarrays
- Cell-specific gene expression: Comparing microarray data using cDNAs derived from RNA of different cell types can identify genes that are expressed in a cell-specific manner.
- Functional microarrays: Consist of many different cellular proteins, used to probe the function of proteins.
Bioinformatics
- The computer has become an important tool in genetic studies, combining genetics and biocomputing to form the field of bioinformatics.
- Computer analysis of genetic sequences relies on three basic components:
- A computer
- A computer program
- Some type of data
Sequence Files and Computer Programs
- A computer program is a defined series of operations that can analyze data in a desired way.
- A computer data file is a collection of information in a form suitable for storage and manipulation by a computer.
- Entering data into a computer file can be done manually or by instruments that read data directly from a sequencing ladder.
Analyzing Genetic Sequences
- Computer analysis of genetic sequences can answer questions such as:
- Does a sequence contain a gene?
- Where are functional sequences, such as promoters and splice sites?
- Does a sequence encode a polypeptide?
- Is a sequence homologous to other sequences?
- What is the evolutionary relationship between two or more genetic sequences?
Homologous Genes
- Homologous genes are genes that have evolved from a common ancestral gene.
- Orthologs: Homologous genes found in different species.
- Paralogs: Homologous genes found in a single organism.
- A gene family consists of two or more copies of homologous genes within the genome of a single organism.
Computer Databases
- Computer databases store large amounts of genetic information generated by researchers.
- Databases contain annotations, including the genetic sequence and a concise description of it, as well as other features of significance.
- Examples of major computer databases include GenBank, EMBL, and DDBJ.
Multiple Sequence Alignment
- This approach compares homologous genes to identify conserved sites and understand their structure and function.
- It was originally proposed by Saul Needleman and Christian Wunsch in 1970.
- The globin gene family in humans is an example of multiple sequence alignment.
Globin Gene Family
- The globin gene family consists of 9 paralogs that are functionally expressed in humans.
- The 9 paralogs fall into two categories: α-chains and β-chains.
- The composition of hemoglobin changes during development, with different genes expressed during early embryonic development and in the adult.
- Comparing the sequences of the hemoglobin chains can give insight into their structure and function.
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Description
Test your understanding of functional genomics, proteomics, and bioinformatics with this quiz. Covers key concepts from Chapter 23 of Genetics: Analysis & Principles by Robert J. Brooker.