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Biotech / Medical : Targeted Gene Repair

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To: John McCarthy who started this subject9/22/2002 9:08:56 PM
From: John McCarthy   of 22
 
TGR - BUZZ_WORDS.....(subject to errors of understanding)
File Created On:09/22/2002 07:52:52 PM

Some words are presented with more than 1 definition.

This post is generated by a program that reads a database and generates this file. Errors will result from incorrect database material. Updates to the database automatically reflected in this file.

Glossery Links
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PhRMA GENOMICS
http://genomics.phrma.org/lexicon/c.html

Glossery of Gene Words
http://www.genome.gov/glossary.cfm

Functional Genomics
http://www.functionalgenomics.org.uk/sections/help/glossary.htm

FAO RESEARCH AND TECHNOLOGY PAPER
http://www.fao.org/DOCREP/003/X3910E/X3910E00.htm#TopOfPage

MWG - The Genetics Company
http://www.mwg-biotech.com/html/glossary/glossary_overview.shtml

Gene Vectors
http://www-micro.msb.le.ac.uk/335/peel/peel1.html

Basic Gene Words
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Chromosome
Very long DNA molecule which includes many genes. The DNA is linked to a large number of different proteins and is thus protected. All cells of an animal or plant type (except for the germ cells) contain the same C characteristic set of chromosomes. Also, the large DNA molecule of the bacteria is called a C. The human being has 46 chromosomes in 2 chromosome sets

Chromosome
The structure in the cell nucleus that contains all of the cellular DNA together with a number of proteins that compact and package the DNA

Chromosome
One of the physically separate segments that together form the genome, or total genetic material, of a cell. Chromosomes are long strands of genetic material or DNA that have been packaged and compressed by wrapping around proteins. The number and size of chromosomes varies from species to species. In humans, there are 23 pairs of chromosomes (a pair has one chromosome from each parent). One pair are called the sex chromosomes because they contain genes that determine sex. The chromosome carrying the male determining genes is designated Y and the corresponding female one the X chromosome. The remaining pairs are called autosomes. Chromosome 1 is the largest and chromosome 22 the smallest. Each chromosome has two “arms” designated p and q.

Gene
a length of DNA which codes for a particular protein, or in certain cases a functional or structural RNA molecule

Gene
Basic unit of hereditary information. A gene consists of a DNA segment, which includes information for the synthesis of RNA. In some cases this RNA itself is the final product. However, it is mostly used for the transport of genetic information to the ribosomes, where proteins are then assembled

Gene
Classically, a unit of inheritance. In practice, a gene is a segment of DNA on a chromosome that encodes a protein and all the regulatory sequences (promoter) required to control expression of that protein.

Gene
Length of DNA that codes for a protein

Gene
Genes are stored in each of our cells, on long twisted strands called DNA (deoxyribonucleic acid), which are distributed among 23 sets of chromosomes. DNA functions like a database that carries information for making proteins that a cell needs, to allow our bodies to properly function. Each gene in turn contains a particular set of instructions to fabricate those proteins.

Gene Expression
the process by which the information in a gene is used to create proteins.

Gene Expression
The conversion of information from gene to protein via transcription and translation.

DNA
ATCG

Nucleotides
adenine (A),

Nucleotides
thymine (T),

Nucleotides
cytosine (C),

Nucleotides
guanine (G)

DNA
the molecule that encodes genetic information. DNA is a double-stranded helix held together by bonds between pairs of nucleotides. See base, base pair, and double helix.

DNA / DNS
Deoxyribonucleic acid: Carrier of the genetic information; structural plan for proteins; the DNA consists of linearly linked nucleotides, whose sequence forms the hereditary information Illustration 1: The DNA, the deoxyribonucleic acid, consists of two strands of linked nucleotides with one of the four bases adenine (A), thymine (T), guanine (G) and cytosine (C). One oxygen atom is missing in the sugar content of the nucleotide - thus the prefix "deoxy". In the sequence of their nucleotides, and thus their bases, both strands are complementary to each other - in each case an A is opposed by a T and a G by a C; this base pairing holds it together. The strands have 3- (referred to as: Three Dash) and a 5'-end and are arranged counter-rotationally.

RNA
ACGU

Nucleotides
adenine (A),

Nucleotides
cytosine (C),

Nucleotides
guanine (G)

Nucleotides
and uracil (U).

RNA
a molecule similar to DNA, which helps in the process of decoding the genetic information carried by DNA.

RNA / RNS
Ribonucleic Acid: Form of genetic information, involved in the translation process from DNA into proteins

RNA (1 OF 2)
A category of nucleic acids which along with DNA forms the genetic material of a cell. While DNA stores the genetic information in the nucleus of every cell, RNA is a “carrier” of this information from DNA to other parts of the cell where the message is converted to protein. Structurally, RNA is a single-stranded structure. The component sugar that forms the backbone of RNA is ribose (as opposed to deoxyribose in DNA) and the four bases in RNA are Uracil, Guanine, Adenine and Cytosine (DNA contains Thymidine instead of Uracil). There are three types of RNA, all of which play an intermediary role in converting DNA information into protein: messenger RNA (mRNA) is a copy of the DNA in the nucleus and carries it to the cytoplasm where the cellular machinery for decoding that information lies; transfer RNA (tRNA) allows the code to be read three bases (one codon) at a time and transfers the information from RNA to protein (each tRNA carries one particular amino acid); and ribosomal RNA (rRNA) has a structural rol

RNA (2 OF 2)
e forming part of the ribosome--the machinery that converts RNA into protein

messenger RNA
the DNA of a gene is transcribed (see transcription) into mRNA molecules, which then serve as a template for the synthesis of proteins.

transcription
the process during which the information in a length of DNA is used to construct an mRNA molecule. Compare translation

Ribosome
the cell structures within which protein synthesis occurs

Ribosomes
Cell components, location where the translation (translation of the genetic information into proteins) takes place

Ribosomes
Small cellular components composed of specialized ribosomal RNA and protein; site of protein synthesis

Knockout mice (gene targeting)
Mice which have been engineered to lack a chosen gene. The gene is inactivated in so called embryonic stem cells using the technique of homologous recombination. These cells are then introduced into a early stage embryo (blastocyst) and this is then transplanted into a recipient mouse. The subsequent progeny lack the targeted gene in some cells. This technique is used to determine the function of the chosen gene.

Enzyme
A protein that acts as a catalyst, speeding the rate at which a biochemical reaction proceeds but not altering the direction or nature of the reaction

Targeted Gene Repair Argot
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Gene Targeting
replacement of native (bad) copy of gene with a corrected copy

Targeted Gene Repair
oligos used to force repair mechanisms to change DNA sequences

Chimeraplasty
Targeted gene correction

Chimeraplasty
The targeted repair or modification of DNA in an organism without the use of viral or other conventional gene delivery vectors. This process is site-specific, i.e. a desirable sequence of DNA is combined with RNA, forming what is known as a chimeraplast. These molecules can be administered intravenously and bind selectively to the portion of the target DNA to be modified. Once bound, the chimeraplast activates a naturally occurring gene-correcting mechanism, which modifies the DNA at the target site precisely. Chimeraplasty is referred to as "precise genetic surgery,'' because DNA is repaired without affecting non-targeted portions of the gene(s). This process is still experimental.

Chimeraplast
The prototypic structure of the chimeraplast was a contiguous stretch of 68 nucleotides containing both RNA and DNA residues. One strand of the heteroduplex structure consisted of a central pentameric block of DNA bases flanked on either side by ten 29-O-methylated RNA residues providing increased resistance to RNaseH enzymatic activity. The complementary strand consisted of all DNA bases. Polythymidine hairpins were placed at both ends to provide stability for secondary structure and a 39 GC clamp to increase nuclease resistance. The 39 and 59 ends were juxtaposed but not joined to allow unwinding of the chimeraplast and greater flexibility to interact with its target sequence and repair proteins.

Chimeric
reflect the fact the molecule consists of different kinds of genetic material

Chimeric RNA/DNA oligonucleotide
See Chimeraplast

Chimeric oligonucleotides
See Chimeraplast

Oligonucleotide
A nucleic acid molecule (DNA or RNA) consisting of a relatively small number of subunits (A,T,G and C for DNA oligonucleotides).

Oligonucleotide
Sequence of a few to many hundreds of nucleotides, linked with each other. An oligonucleotide thus corresponds to a (very) short DNA single strand

Oligonucleotide
A short molecule consisting of several linked nucleotides (typically between 10 and 60) covalently attached by phosphodiester bonds

Oligo
synthetic paperclip-shaped oligonucleotide

Antisense oligonucleotides
Single stranded oligodeoxynucleotides directed against a particular gene or mRNA which block transcription or translation through sequence-specific hybridisation with targeted gene sequences.

Antisense oligonucleotides
A short string of nucleotides that can bond to messenger RNA (mRNA) and block the process of gene expression

RDO
RNA/DNA D31

TGR Focus Words
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Exon
The protein-coding DNA sequence of a gene

Intron
A length of DNA which is interspersed among the protein-coding sequences (exons) in a gene. Introns are transcribed (see transcription) into mRNA but are then cut out of the mRNA sequence before protein synthesis occurs

Codon
A sequence of three adjacent nucleotides that designates a specific amino acid or start/stop site for transcription

Frameshift
A deletion, substitution, or duplication of one or more bases that causes the reading-frame of a structural gene to shift from the normal series of triplets

Hairpin
A double-helical region in a single DNA or RNA strand formed by the hydrogen-bonding between adjacent inverse complementary sequences to form a hairpin shaped structure

In vivo
Pertaining to a biological process or reaction taking place in a living cell or organism. Compare to ex vivo and in vitro

In vivo gene therapy
Gene repair or alteration performed within an individual organism. Examples include the insertion of genes into lung cells of patients suffering from cystic fibrosis

Ex vivo
[latin] Pertaining to a biological process or reaction taking place outside of a living cell or organism

In vitro
Pertaining to a biochemical process or reaction taking place in a test-tube (or more broadly, in a lab) as opposed to taking place in a living cell or organism. Compare to in vivo.

In situ hybridization
Use of a DNA or RNA probe to detect the presence of the complementary DNA sequence in cloned bacterial or cultured eukaryotic cells.

Recessive allele
An allele which will only result in a specific phenotype when its counterpart allele is also recessive, or when no counterpart allele exists. "Autosomal recessive disorders" develop in individuals who inherit two mutant copies of a gene which is located on one of the autosomes. When a recessive gene associated with disease occurs on certain parts of the X chromosome, the disease (hemophilia is an example) is known as an "X-linked recessive disorder." X-linked recessive disorders may occur more often in men than in women, because men inherit only one copy of the gene (since they have only one X chromosome). Compare dominant allele.

Stem cell
Undifferentiated, primitive cells in the bone marrow that have the ability both to multiply and to differentiate into specific blood cells (See also Embryonic stem cells)

Wild type
The form of an organism that occurs most frequently in nature

Eukaryote
Cell or organism with membrane-bound, structurally discrete nucleus and other well-developed subcellular compartments. Eukaryotes include all organisms except viruses, bacteria, and bluegreen algae.

Vector
1] An organism which serves to transfer a disease causing organism (pathogen) from one organism to another. [2] a mechanism whereby foreign gene(s) are moved into an organism and inserted into that organism's genome. Retroviruses such as HIV serve as vectors by inserting genetic information (DNA ) into the genome of human cells. Bacteria can serve as vectors in plant populations.

Electroporation
A process using high-voltage current to make cell membranes permeable to allow the introduction of new DNA; commonly used in recombinant DNA technology.

Southern blotting
Transfer by absorption of DNA fragments separated in electrophoretic gels to membrane filters for detection of specific base sequences by radio-labeled complementary probes

E. coli (Escherichia coli)
Common bacterium that has been studied intensively by geneticists because of its small genome size, normal lack of pathogenicity, and ease of growth in the laboratory.

GENE VECTORS
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Adenoviruses
no integration / transient

Adeno-associated virus (AAV)
are non-pathogenic human parvoviruses, dependant on a helper virus, usually adenovirus, to proliferate. They are capable of infecting both dividing & non dividing cells, & in the absence of a helper virus integrate into a specific point of the host genome (19q 13-qter) at a high frequency (Kotin et al, 1990).

Retroviruses
disarmed or "gutted" / no control over

Lipofection - liposomes
tiny membrane-bound spheres loaded with DNA

Antisense and RNAi technology
can inhibit expression of genes very selectively

Overexpress mutant gene
insert somewhere and crank out good protein

Electroporation
Zap them just like E. coli

DISEASE
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Sickle cell anemia
a single letter misspelled, in the gene encoding the b-globin strand of hemoglobin

Cystic fibrosis
Over 70 percent of the cases of cystic fibrosis are attributable to the deletion of three nucleotides in the CFTR gene

Muscular dystrophy
Lack of a protein called dystrophin

Crigler-Najjar syndrome
crucial enzyme UGT is either missing or is decreased in quantity or activity

Generalised Atrophic Benign Epidermolysis Bullosa (GABEB)
genetic disorders causing blistering and shearing of the skin from even the gentlest friction, often from everyday activities

Single-gene disorder
Hereditary disorder caused by a mutant allele of a single gene (e.g., Duchenne muscular dystrophy, retinoblastoma, sickle cell disease).

Hereditary
Hereditary mutations are mistakes that are present in the DNA of virtually all body cells and are transmitted from generation to generation

Acquired
Acquired mutations on the other hand are changes in DNA that happen throughout a lifetime and are usually only present in the DNA of an individual cell. These mutations usually happen during cell division or can also be the aftermath of environmental stresses. Mutations usually rectify on their own, but the repair mechanism can sometimes fail causing permanent damage.

Disease Number
More than 5,000 human diseases are linked to a single gene being abnormal

PRODUCTS
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Reagents
Reaction solutions and enzymes, used to carry out chemical or enzymatic reaction sequences

OFF TOPIC
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Wonderful Story
http://www.the-scientist.com/yr2001/mar/research_010305.html
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