A hashing algorithm developed by Jim Kent to allow rapid searching of large amounts of genome sequence. A hashing algorithm divides the database into words of a prescribed size (often 12-14 bases). The locations of these words are stored in memory. The query sequence is scanned for exact matches to words stored in memory. These types of algorithms tend to be very fast and effective for closely related sequences, but fail as sequences diverge.
In addition to nucleotide BLAT, translated BLAT allows for comparison of protein sequences.
This sequence aligner also allows for accurate alignment of transcribed sequences by looking at splice site information.
reference:
Kent WJ. BLAT- the BLAST like alignment tool. Genome Res 2002; 12(4):656-64.

Coding sequence. This is the portion of an mRNA or genomic sequence that encodes for a protein sequence.

These are events that are mediated by double-strand breaks and subsequent repair occurring in the genome. When these breaks are repaired the location of landmarks in the genome have often changed or have been removed completely. There are many different types of rearrangements:

• deletion: the removal of a DNA sequence.
• insertion: the addition of a DNA sequence
• translocation: fusing one part of a chromosome to another
• inversion: this is an intra-chromosomal event in which two breaks occur on the chromosome, the piece in the middle is flipped and the ends are then repaired.

These events may have no phenotypic consequences, depending upon the amount of DNA involved and the location of the breakpoints. However, there are many well-characterized human syndromes that are associated with these events.
Read more about chromosomal rearrangements.
Learn more about rearrangements associated with cancer.
reference:
Inoue K, Lupski JR. Molecular mechanisms for genomic disorders.Annu Rev Genomics Hum Genet 2002; 3:199-242.

This is short for contiguous sequence. When two sequences overlap at their ends (known as a "dove-tail" overlap). The sequences can be collapsed into a single, non-redundant sequence.
Read more about contigs
references:
Jang W et al (1999) Making effective use of human genomic sequence data. Trends Genet. 15(7): 284-6.
Kent WJ and Haussler D (2001) Assembly of the working draft of the human genome with GigAssembler. Genome Res 11(9): 1541-8.
Agarwala R et al (Manuscript in preparation).

Cloning vector that typically contains insert sizes of 60-120kb. These vectors are hybrids of lambda phages and plasmids and can be propagated as plasmids or packaged like phage. The name comes from the fact that these vectors retain the phage cos sites that are used for lambda head stuffing. These are generally maintained in multiple copies in E. coli.
Read more about cosmids
references:
Evans GA et al. High efficiency vectors for cosmid microcloning and genomic analysis. Gene 1989; 79(1):9-20.
Coulsan A et al. The physical map of the Caenorhabditis elegans genome. Methods Cell Biol 1995; 48:533-50.

This term has had several definitions, but generally refers to sequence that is not yet finished but is of generally high quality. In terms of clone based project, Draft sequence refers to a project in which greater than 90% of the bases are of high quality. This means that a clone project will have several fragments connected by Ns. Often, the order and orientation of these fragments is unknown. However, these sequences, in conjunction with other data are a useful substrate for genome assembly and annotation.
See HTGS for additional information.
references:
Collins FS et al. New goals for the U.S. Human Genome Project: 1998-2003. Science 1998; 282(5389):682-9.
The Human Genome Sequence Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822):860-921.

Expressed sequence tag. These are single-pass sequences of cDNA clones. Databases of EST sequences are highly redundant but quite useful for gene identification. There are many efforts to cluster EST sequences to remove the redundancy and low-quality sequences.
EST clusters in UniGene
Gene indexes at TIGR
EST clusters at Allgenes
references:
Adams MD et al. Complementary DNA sequencing: expressed sequence tags and human genome project. Science 1991; 252(5013):1651-6.
Marra M et al. An encyclopedia of mouse genes. Nat Genet 1999; 21(2):191-4.

A technique that utilizes Whole Genome Shotgun (WGS) reads from the pufferfish, Tetraodan nigroviridis, to identify potential coding sequences in mammalian genomes based on homology. This technique was first used to annotate the Human Genome.
Read more about exoFISH
reference:
Roest Crollius et al. Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence. Nat Genet 2000; 25(2):235-8.

A clone insert has been sequenced with an error rate of <0.01%. These sequence records generally have no gaps.
references:
Collins FS et al. New goals for the US Human Genome Project: 1998-2003. Science 1998; 282(5389):682-9.
The Human Genome Sequence Consortium Initial sequencing and analysis of the human genome. Nature 2001; 409(6822):860-921.

Fluorescent in situ hybridization. Genomic clones are fluorescently labeled and hybridized to chromosome spreads. In this way a clone can be mapped to a discrete cytogenetic band. If the clone has sequence associated with it, this information can be used to integrate sequence with cytogenetic information.
Read more about FISH
FISH methodology
reference:
Dyer SA and Green EK. Fluorescent in situ hybridization. Methods Mol Biol 2002; 187:73-86.

This is a specific type of transgenesis that targets a particular gene. If a mutated copy of a gene is electroporated into a cell, the inserted DNA will find the endogenous copy of itself and recombination will occur with some frequency (1-25%). If this event occurs in embryonic stem cells, cells carrying the new copy of the gene can be used to generate embryos that can be assessed for the phenotypic consequences of the mutation. This technique is used frequently in mice to study
loss-of -function mutations.
Read more about gene targeting
references:
Thomas et al. High frequency targeting of genes to specific sites in the mammalian genome. Cell 1986; 44(3):419-28.
van der Weyden L, et al. Tools for targeted manipulation of the mouse genome. Physiol Genomics 2002; 11(3):133-64.

This strategy uses transgenesis to introduce DNA carrying a reporter gene (lacZ or GFP) flanked by various genomic signals (splice donor or acceptor sites, promoters, etc.). Expression of the reporter gene indicates that the DNA has integrated into a region of the genome containing a gene. The gene that has been trapped can be recovered using the DNA sequences associated with the reporter construct. Often, the introduction of the gene trapping vector inactivates the gene into which it was introduced.
Go to the Gene Trap web page
references:
Gossler et al. Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. Science 1989; 244(4903):463-5.
Stanford et al. Gene-trap mutagenesis: past, present and beyond. Nat Rev Genet 2001; 2(10):756-68.

A sequence variation that deviates from the reference, or "wild type", sequence. This variation can be a SNP, an insertion of sequence, or a deletion of sequence. There can be a great deal of sequence variation between individuals in a population. For example, different humans may have as many as 1 basepair difference every 1000 bp. In practice, mutations are distinguished from variation because they have phenotypic consequences. Mutations in the Pax6 gene that lead to a loss of the function of that gene lead to the eyeless mutation in flies, the Small eye mutation in mice, and aniridia in humans.
Read more about mutations and mutant analysis
reference:
Gehring WJ. The master control gene for morphogenesis and evolution of the eye. Genes Cells 1996; 1(1):11-5.

An observable characteristic displayed by an organism. These characteristics can be controlled by genes, by the environment, or a combination of both. The characteristic can be directly observable, such as having brown eyes. In some cases, the phenotype will be measurable, such as having high blood pressure.
OMIM is an on-line catalog of human phenotypes

Identification of a gene based on its physical location in the genome. Often, an individual has a phenotype, but the gene underlying this phenotype is unknown. Using linkage mapping, the phenotype can be assigned a position in the genome. Once a phenotype has been localized, overlapping sets of clones (for example, BACs) that cover the region are identified. Genes within the region are identified and compared to DNA from individuals that display the phenotype until the underlying mutation is identified.
Read more about positional cloning
references:
Kerem B, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 8;245(4922):1073-80.

Reference Sequence. The goal of the RefSeq project is to produce a reference sequence for all naturally occurring molecules from the central dogma (DNA, RNA, Protein).
reference:
Pruitt KD, Maglott DR. RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res 2001; 29(1):137-140.

Restriction fragment length polymorphism. A type of polymorphism detectable in a genome by the size differences in DNA fragments generated by restriction enzyme analysis.
Read more about RFLPs
references:
Botstein D, et al. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 1980; 32(3):314-31.
Donis-Keller H, et al. A genetic linkage map of the human genome. Cell 1987; 51(2):319-37.

Radiation Hybrid mapping. A physical mapping method that estimates linkage and distance relative to radiation-induced chromosome breaks. This is analogous to genetic mapping.
More on RH mapping
references:
Goss SJ, Harris H. New method for mapping genes in human chromosomes. Nature 1975; 255(5511):680-4.
Cox et al. Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 1990; 250(4978):245-50.
Hudson TJ, et al. A radiation hybrid map of mouse genes. Nat Genet 2001; 29(2):201-5.

Simple sequence length polymorphisms. Common examples of these in mammalian genomes include runs of dinucleotide or trinucleotide repeats (CACACACACACACACACA).
Read more about SSLPs
reference:
Weissenbach J, et al. A second-generation linkage map of the human genome. Nature 1992; 29:359(6398):777-8.

Most cells of the adult body are terminally differentiated, that is, they are no longer able to replace themselves or to become another cell type. Stem cells are undifferentiated cells that are able to both proliferate and differentiate into numerous cell types. For example, embryonic stem cells are able to differentiate into any cell type found within the embryo, where as hematopoietic stem cells can differentiate into any blood cell.
Read more about stem cells
reference:
Rossant J. Stem cells from the Mammalian blastocyst. Stem Cells 2001; 19(6):477-82

Sequence Tag Site. In general, short sequences (200-500 bp) are produced throughout a genome. Oligonucleotide primers are generated such that this sequence can be amplified using PCR to produce a discrete band when analyzed by electrophoresis. STS markers can be polymorphic or monomorphic. They are critical to integrating non-sequence based maps (such as genetic or RH) with sequence based maps.
Read more about STSs
references:
Green ED, Green P. Sequence-tagged site (STS) content mapping of human chromosomes: theoretical considerations and early experiences. PCR Methods Appl 1991; 1(2):77-90.
Hudson TJ et al. An STS-based map of the human genome. Science 1995; 270(5244):1919-20.

A supercontig is formed when an association can be made between two contigs that have no sequence overlap. This commonly occurs using information obtained from paired plasmid ends. For example, both ends of a BAC clone are sequenced. It can be inferred that these two sequences are approximately 150-200 Kb apart (based on the average size of a BAC). If the sequence from one end is found in a particular sequence contig, and the sequence from the other end is found in a different sequence contig, the two sequence contigs are said to be linked. In general, it is useful to have end sequences from more than one clone to provide evidence for linkage.

Whole Genome Shotgun. A sequencing method by which an entire genome is cut into chunks of discrete sizes (usually 2,10, 50 and 150 Kb) and cloned into an appropriate vector. The ends of these clones are sequenced. The two ends from the same clone are referred to as mate pairs. The distance between two mate pairs can be inferred if the library size is known and should have a narrow window of deviation.
references:
Weber JL, Myers EW. Human whole-genome shotgun sequencing. Genome Res 1997; 7(5): 401-409.
Venter JC et al. The sequence of the human genome. Science 2001; 291(5507):1304-51.
Batzogluo S et al. ARACHNE: a whole-genome shotgun assembler. Genome Res 2002; 12(1):177-89.
Mullikin JC, Ning Z. The phusion assembler. Genome Res 2003; 13(1):81-90.