Gene maps help describe the spatial arrangement of genes on a

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

. Genes are designated to a specific location on a chromosome known as the

locus Locus (plural loci) is Latin for "place". It may refer to: Entertainment * Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front * ''Locus'' (magazine), science fiction and fantasy magazine ** ''Locus Award' ...

and can be used as

molecular markers A molecular marker is a molecule, sampled from some source, that gives information about its source. For example, DNA is a molecular marker that gives information about the organism from which it was taken. For another example, some proteins can be ...

to find the distance between other genes on a chromosome. Maps provide researchers with the opportunity to predict the inheritance patterns of specific traits, which can eventually lead to a better understanding of disease-linked traits. The genetic basis to gene maps is to provide an outline that can potentially help researchers carry out

DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...

. A gene map helps point out the relative positions of genes and allows researchers to locate regions of interest in the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

. Genes can then be identified quickly and

sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...

quickly. Two approaches to generating gene maps include physical mapping and genetic mapping. Physical mapping utilizes molecular biology techniques to inspect chromosomes. These techniques consequently allow researchers to observe chromosomes directly so that a map may be constructed with relative gene positions. Genetic mapping on the other hand uses genetic techniques to indirectly find association between genes. Techniques can include cross-breeding (see

Hybrid (biology) In biology, a hybrid is the offspring resulting from combining the qualities of two organisms of different breeds, varieties, species or genera through sexual reproduction. Hybrids are not always intermediates between their parents (such as in ...

) experiments and examining pedigrees. These technique allow for maps to be constructed so that relative positions of genes and other important sequences can be analyzed.

Physical mapping

Physical mapping techniques used to generate a gene map include: Restriction mapping, Fluorescent ''in situ'' hybridization (FISH), and Sequence tagged site (STS) mapping.

Restriction mapping

Restriction map A restriction map is a map of known restriction sites within a sequence of DNA. Restriction mapping requires the use of restriction enzymes. In molecular biology, restriction maps are used as a reference to engineer plasmids or other relatively ...

ping is a method in which structural information regarding a segment of DNA is obtained using restriction enzymes. Restriction enzymes are

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s that help cut segments of DNA at specific recognition sequences. The basis to restriction mapping involves digesting (or cutting) DNA with restriction enzymes. The digested DNA fragments are then run on an agarose gel using electrophoresis, which provides one with information regarding the size of these digested fragments. The sizes of these fragments help indicate the distance between restriction enzyme sites on the DNA analyzed, and provides researchers with information regarding the structure of DNA analyzed.

Fluorescent ''in situ'' hybridization (FISH)

FISH Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...

is a method used to detect the presence (or absence) of a DNA sequence within a cell. DNA probes that are specific for chromosomal regions or genes of interest are labeled with fluorochromes. By attaching fluorochromes to probes, researchers are able to visualize multiple DNA sequences simultaneously. When a probe comes into contact with DNA on a specific chromosome, hybridization will occur. Consequently, information regarding the location of that sequence of DNA will be attained. FISH analyzes single stranded DNA ( ssDNA). Once the DNA is in its single stranded state, the DNA can bind to its specific probe.

Sequence-tagged site (STS) mapping

sequence-tagged site A sequence-tagged site (or STS) is a short (200 to 500 base pair) DNA sequence that has a single occurrence in the genome and whose location and base sequence are known. Usage STSs can be easily detected by the polymerase chain reaction (PCR) usin ...

(STS) is a short sequence of DNA (about 100 - 500

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s in length) that is seen to appear multiple times within an individual's genome. These sites are easily recognizable, usually appearing at least once in the DNA being analyzed. These sites usually contain genetic polymorphisms making them sources of viable genetic markers (as they differ from other sequences). Sequenced tagged sites can be mapped within our genome and require a group of overlapping DNA fragments. PCR is generally used to produce the collection of DNA fragments. After overlapping fragments are created, the map distance between STSs can be analyzed. In order to calculate the map distance between STSs, researchers determine the frequency at which breaks between the two markers occur (see

shotgun sequencing In genetics, shotgun sequencing is a method used for sequencing random DNA strands. It is named by analogy with the rapidly expanding, quasi-random shot grouping of a shotgun. The chain-termination method of DNA sequencing ("Sanger sequencing ...

)

Genetic mapping

Genetic mapping is focused on the principles first established by

Gregor Mendel Gregor Johann Mendel, Augustinians, OSA (; cs, Řehoř Jan Mendel; 20 July 1822 – 6 January 1884) was a biologist, meteorologist, mathematician, Augustinians, Augustinian friar and abbot of St Thomas's Abbey, Brno, St. Thomas' Abbey in Br� ...

. This approach primarily focuses on linkage analysis and gene association techniques.

Linkage analysis

The basis to

linkage analysis Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separ ...

is understanding chromosomal location and identifying disease genes. Certain genes that are linked or associated with each other are found to reside close to each other on the same chromosome. During

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...

, these genes are capable of being inherited together and can be used as a

genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...

to help identify the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

of diseases. Because linkage analysis can identify inheritance patterns, these studies are usually family based.

Gene association analysis

Gene association analysis is population based; it is not focused on inheritance patterns, but rather is based on the entire history of a population. Gene association analysis looks at a particular population and tries to identify whether the frequency of an

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

in affected individuals is different from that of a control set of unaffected individuals of the same population. This method is particularly useful to identify complex diseases that do not have a

Mendelian inheritance Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularize ...

pattern.

Utilizing gene maps: disease genes

Using the methods mentioned above, researchers are capable of mapping disease genes. Generating a gene map is the critical first step towards identifying disease genes. Gene maps allow for variant alleles to be identified and allow for researchers to make predictions about the genes they think are causing the

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

phenotype. An example of a disorder that was identified by Linkage analysis is

Cystic Fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

. For example, with Cystic Fibrosis (CF), DNA samples from fifty families affected by CF were analyzed using linkage analysis. Hundreds of markers pertaining to CF were analyzed throughout the genome until CF was identified on the long arm of chromosome 7. Researchers then had completed linkage analysis on additional DNA markers within chromosome 7 to identify an even more precise location of the CF gene. They found that the CF gene resides around 7q31-q32 (see chromosomal nomenclature).

References

{{DEFAULTSORT:Gene Map Genetic mapping Genes