Linkage Mapping

The observations by Thomas Hunt Morgan that the amount of crossing over between linked genes differs led to the idea that crossover frequency might indicate the distance separating genes on the chromosome. Morgan's student Alfred Sturtevant developed the first genetic map, also called a linkage map.

Sturtevant proposed that the greater the distance between linked genes, the greater the chance that non-sister chromatids would cross over in the region between the genes. By working out the number of recombinants it is possible to obtain a measure for the distance between the genes. This distance is called a genetic map unit (m.u.), or a centimorgan and is defined as the distance between genes for which one product of meiosis in 100 is recombinant. A recombinant frequency (RF) of 1 % is equivalent to 1 m.u. A linkage map is created by finding the map distances between a number of traits that are present on the same chromosome, ideally avoiding having significant gaps between traits to avoid the inaccuracies that will occur due to the possibility of multiple recombination events.

Linkage mapping is critical for identifying the location of genes that cause genetic diseases. In an ideal population, genetic traits and markers will occur in all possible combinations with the frequencies of combinations determined by the frequencies of the individual genes. For example, if alleles A and a occur with frequency 90% and 10%, and alleles B and b at a different genetic locus occur with frequencies 70% and 30%, the frequency of individuals having the combination AB would be 63%, the product of the frequencies of A and B, regardless of how close together the genes are. However, if a mutation in gene B that causes some disease happened recently in a particular subpopulation, it almost always occurs with a particular allele of gene A if the individual in which the mutation occurred had that variant of gene A and there have not been sufficient generations for recombination to happen between them (presumably due to tight linkage on the genetic map). In this case, called linkage disequilibrium, it is possible to search potential markers in the subpopulation and identify which marker the mutation is close to, thus determining the mutation's location on the map and identifying the gene at which the mutation occurred. Once the gene has been identified, it can be targeted to identify ways to mitigate the disease.

http://en.wikipedia.org/wiki/Genetic_mapping

Genetic linkage

Genetic linkage occurs when particular genetic loci or alleles for genes are inherited jointly. Genetic loci on the same chromosome are physically connected and tend to segregate together during meiosis, and are thus genetically linked. Alleles for genes on different chromosomes are usually not linked, due to independent assortment of chromosomes during meiosis.

Because there is some crossing over of DNA when the chromosomes segregate, alleles on the same chromosome can be separated and go to different daughter cells. There is a greater probability of this happening if the alleles are far apart on the chromosome, as it is more likely that a cross-over will occur between them.

The relative distance between two genes can be calculated using the offspring of an organism showing two linked genetic traits, and finding the percentage of the offspring where the two traits do not run together. The higher the percentage of descendents that does not show both traits, the further apart on the chromosome they are.

Among individuals of an experimental population or species, some phenotypes or traits occur randomly with respect to one another in a manner known as independent assortment. Today scientists understand that independent assortment occurs when the genes affecting the phenotypes are found on different chromosomes.

An exception to independent assortment develops when genes appear near one another on the same chromosome. When genes occur on the same chromosome, they are usually inherited as a single unit. Genes inherited in this way are said to be linked, and are referred to as "linkage groups." For example, in fruit flies the genes affecting eye color and wing length are inherited together because they appear on the same chromosome.

But in many cases, even genes on the same chromosome that are inherited together produce offspring with unexpected allele combinations. This results from a process called crossing over. At the beginning of normal meiosis, a chromosome pair (made up of a chromosome from the mother and a chromosome from the father) intertwine and exchange sections or fragments of chromosome. The pair then breaks apart to form two chromosomes with a new combination of genes that differs from the combination supplied by the parents. Through this process of recombining genes, organisms can produce offspring with new combinations of maternal and paternal traits that may contribute to or enhance survival.

Genetic linkage was first discovered by the British geneticists William Bateson and Reginald Punnett shortly after Mendel's laws were rediscovered.

http://en.wikipedia.org/wiki/Genetic_mapping

Genomics

Genomics is the study of an organism's entire genome. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis, epistasis, pleiotropy and other interactions between loci and alleles within the genome. In contrast, the investigation of single genes, their functions and roles, something very common in today's medical and biological research, and a primary focus of molecular biology, does not fall into the definition of genomics, unless the aim of this genetic, pathway, and functional information analysis is to elucidate its effect on, place in, and response to the entire genome's networks.

History of the field

Genomics can be said to have appeared in the 1980s, and took off in the 1990s with the initiation of genome projects for several biological species. A major branch of genomics is still concerned with sequencing the genomes of various organisms, but the knowledge of full genomes has created the possibility for the field of functional genomics, mainly concerned with patterns of gene expression during various conditions. The most important tools here are microarrays and bioinformatics. Study of the full set of proteins in a cell type or tissue, and the changes during various conditions, is called proteomics.

In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent (Ghent, Belgium) were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.^[1] In 1976, the team determined the complete nucleotide-sequence of bacteriophage MS2-RNA.^[2] The first DNA-based genome to be sequenced in its entirety was that of bacteriophage Φ-X174; (5,368 bp), sequenced by Frederick Sanger in 1977^[3]. The first free-living organism to be sequenced was that of Haemophilus influenzae (1.8 Mb) in 1995, and since then genomes are being sequenced at a rapid pace. A rough draft of the human genome was completed by the Human Genome Project in early 2001, creating much fanfare.

As of September 2007, the complete sequence was known of about 1879 viruses ^[4], 577 bacterial species and roughly 23 eukaryote organisms, of which about half are fungi. ^[5] Most of the bacteria whose genomes have been completely sequenced are problematic disease-causing agents, such as Haemophilus influenzae. Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast (Saccharomyces cerevisiae) has long been an important model organism for the eukaryotic cell, while the fruit fly Drosophila melanogaster has been a very important tool (notably in early pre-molecular genetics). The worm Caenorhabditis elegans is an often used simple model for multicellular organisms. The zebrafish Brachydanio rerio is used for many developmental studies on the molecular level and the flower Arabidopsis thaliana is a model organism for flowering plants. The Japanese pufferfish (Takifugu rubripes) and the spotted green pufferfish (Tetraodon nigroviridis) are interesting because of their small and compact genomes, containing very little non-coding DNA compared to most species. ^{[6] [7]} The mammals dog (Canis familiaris), ^[8] brown rat (Rattus norvegicus), mouse (Mus musculus), and chimpanzee (Pan troglodytes) are all important model animals in medical research.

Bacteriophage Genomics

Bacteriophages have played and continue to play a key role in bacterial genetics and molecular biology. Historically, they were used to define gene structure and gene regulation. Also the first genome to be sequenced was a bacteriophage. However, bacteriophage research did not lead the genomics revolution, which is clearly dominated by bacterial genomics. Only very recently has the study of bacteriophage genomes become prominent, thereby enabling researchers to understand the mechanisms underlying phage evolution. Bacteriophage genome sequences can be obtained through direct sequencing of isolated bacteriophages, but can also be derived as part of microbial genomes. Analysis of bacterial genomes has shown that a substantial amount of microbial DNA consists of prophage sequences and prophage-like elements. A detailed database mining of these sequences offers insights into the role of prophages in shaping the bacterial genome.^[9]

Cyanobacteria Genomics

At present there are 24 cyanobacteria for which a total genome sequence is available. 15 of these cyanobacteria come from the marine environment. These are six Prochlorococcus strains, seven marine Synechococcus strains, Trichodesmium erythraeum IMS101 and Crocosphaera watsonii [[WH8501. Several studies have demonstrated how these sequences could be used very successfully to infer important ecological and physiological characteristics of marine cyanobacteria. However, there are many more genome projects currently in progress, amongst those there are further Prochlorococcus and marine Synechococcus isolates, Acaryochloris and Prochloron, the N₂-fixing filamentous cyanobacteria Nodularia spumigena, Lyngbya aestuarii and Lyngbya majuscula, as well as bacteriophages infecting marine cyanobaceria. Thus, the growing body of genome information can also be tapped in a more general way to address global problems by applying a comparative approach. Some new and exciting examples of progress in this field are the identification of genes for regulatory RNAs, insights into the evolutionary origin of photosynthesis, or estimation of the contribution of horizontal gene transfer to the genomes that have been analyzed.^[10]

http://en.wikipedia.org/wiki/Genomics

Genome - Types

Most biological entities more complex than a virus sometimes or always carry additional genetic material besides that which resides in their chromosomes. In some contexts, such as sequencing the genome of a pathogenic microbe, "genome" is meant to include this auxiliary material, which is carried in plasmids. In such circumstances then, "genome" describes all of the genes and non-coding DNA that have the potential to be present.

In vertebrates such as sheep and other various animals however, "genome" carries the typical connotation of only chromosomal DNA. So although human mitochondria contain genes, these genes are not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome, often referred to as the "mitochondrial genome".

Genomes and genetic variation

Note that a genome does not capture the genetic diversity or the genetic polymorphism of a species. For example, the human genome sequence in principle could be determined from just half the DNA of one cell from one individual. To learn what variations in DNA underlie particular traits or diseases requires comparisons across individuals. This point explains the common usage of "genome" (which parallels a common usage of "gene") to refer not to any particular DNA sequence, but to a whole family of sequences that share a biological context.

Although this concept may seem counter intuitive, it is the same concept that says there is no particular shape that is the shape of a cheetah. Cheetahs vary, and so do the sequences of their genomes. Yet both the individual animals and their sequences share commonalities, so one can learn something about cheetahs and "cheetah-ness" from a single example of either.

http://en.wikipedia.org/wiki/Genome

Human genome

A graphical representation of the normal human karyotype.

The human genome is the genome of Homo sapiens, which has 24 distinct chromosomes (22 autosomal + X + Y) with a total of approximately 3 billion DNA base pairs containing an estimated 20,000–25,000 genes. ^[1] The Human Genome Project has produced a reference sequence of the euchromatic human genome, which is used worldwide in biomedical sciences. The human genome had fewer genes than expected, with only about 1.5% coding for proteins, and the rest comprised by RNA genes, regulatory sequences, introns and controversially so-called junk DNA.^[2]

Features

Chromosomes

The human genome is composed of 23 pairs of chromosomes (46 in total), each of which contain hundreds of genes separated by intergenic regions. Intergenic regions may contain regulatory sequences and non-coding DNA.

There are 24 distinct human chromosomes: 22 autosomal chromosomes, plus the sex-determining X and Y chromosomes. Chromosomes 1–22 are numbered roughly in order of decreasing size. Somatic cells usually have 23 chromosome pairs: one copy of chromosomes 1–22 from each parent, plus an X chromosome from the mother, and either an X or Y chromosome from the father, for a total of 46.

Genes

There are an estimated 20,000–25,000 human protein-coding genes ^[1]

Surprisingly, the number of human genes seems to be less than a factor of two greater than that of many much simpler organisms, such as the roundworm and the fruit fly. However, human cells make extensive use of alternative splicing to produce several different proteins from a single gene, and the human proteome is thought to be much larger than those of the aforementioned organisms.

Most human genes have multiple exons, and human introns are frequently much longer than the flanking exons.

Human genes are distributed unevenly across the chromosomes. Each chromosome contains various gene-rich and gene-poor regions, which seem to be correlated with chromosome bands and GC-content. The significance of these nonrandom patterns of gene density is not well understood. In addition to protein coding genes, the human genome contains thousands of RNA genes, including tRNA, ribosomal RNA, microRNA, and other non-coding RNA genes.

Regulatory sequences

The human genome has many different regulatory sequences which are crucial to controlling gene expression. These are typically short sequences that appear near or within genes. A systematic understanding of these regulatory sequences and how they together act as a gene regulatory network is only beginning to emerge from computational, high-throughput expression and comparative genomics studies.

Identification of regulatory sequences relies in part on evolutionary conservation. The evolutionary branch between the human and mouse, for example, occurred 70–90 million years ago.^[3] So computer comparisons of gene sequences that identify conserved non-coding sequences will be an indication of their importance in duties such as gene regulation. ^[4]

Another comparative genomic approach to locating regulatory sequences in humans is the gene sequencing of the puffer fish. These vertebrates have essentially the same genes and regulatory gene sequences as humans, but with only one-eighth the "junk" DNA. The compact DNA sequence of the puffer fish makes it much easier to locate the regulatory genes.^[5]

Other DNA

Protein-coding sequences (specifically, coding exons) comprise less than 1.5% of the human genome.^[2] Aside from genes and known regulatory sequences, the human genome contains vast regions of DNA the function of which, if any, remains unknown. These regions in fact comprise the vast majority, by some estimates 97%, of the human genome size. Much of this is comprised of:

elements

• Tandem repeats
  • Satellite DNA
  • Minisatellite
  • Microsatellite
• Interspersed repeats
  • SINEs
  • LINEs

transposons

• Retrotransposons
  • LTR
    • Ty1-copia
    • Ty3-gypsy
  • Non-LTR
    • SINEs
    • LINEs
• DNA Transposons

pseudogenes

However, there is also a large amount of sequence that does not fall under any known classification.

Much of this sequence may be an evolutionary artifact that serves no present-day purpose, and these regions are sometimes collectively referred to as "junk" DNA. There are, however, a variety of emerging indications that many sequences within are likely to function in ways that are not fully understood. Recent experiments using microarrays have revealed that a substantial fraction of non-genic DNA is in fact transcribed into RNA,^[6] which leads to the possibility that the resulting transcripts may have some unknown function. Also, the evolutionary conservation across the mammalian genomes of much more sequence than can be explained by protein-coding regions indicates that many, and perhaps most, functional elements in the genome remain unknown.^[7] The investigation of the vast quantity of sequence information in the human genome whose function remains unknown is currently a major avenue of scientific inquiry. ^[8]

Variation

Most studies of human genetic variation have focused on single nucleotide polymorphisms (SNPs), which are substitutions in individual bases along a chromosome. Most analyses estimate that SNPs occur on average somewhere between every 1 in 100 and 1 in 1,000 base pairs in the euchromatic human genome, although they do not occur at a uniform density. Thus follows the popular statement that "we are all, regardless of race, genetically 99.9% the same", ^[9] although this would be somewhat qualified by most geneticists. For example, a much larger fraction of the genome is now thought to be involved in copy number variation. ^[10] A large-scale collaborative effort to catalog SNP variations in the human genome is being undertaken by the International HapMap Project.

The genomic loci and length of certain types of small repetitive sequences are highly variable from person to person, which is the basis of DNA fingerprinting and DNA paternity testing technologies. The heterochromatic portions of the human genome, which total several hundred million base pairs, are also thought to be quite variable within the human population (they are so repetitive and so long that they cannot be accurately sequenced with current technology). These regions contain few genes, and it is unclear whether any significant phenotypic effect results from typical variation in repeats or heterochromatin.

Most gross genomic mutations in germ cells probably result in inviable embryos; however, a number of human diseases are related to large-scale genomic abnormalities. Down syndrome, Turner Syndrome, and a number of other diseases result from nondisjunction of entire chromosomes. Cancer cells frequently have aneuploidy of chromosomes and chromosome arms, although a cause and effect relationship between aneuploidy and cancer has not been established.

http://en.wikipedia.org/wiki/Human_genome

Philips to Unveil 52-inch Multi-Touch LCD at CES

Philips says it will unveil a 52-inch multi-touch LCD at next week's Consumer Electronics Show.

LG.Philips LCD is planning to unveil a 52-inch multi-touch LCD (liquid crystal display) at next week's Consumer Electronics Show, it said Monday. The screen is 5-inches larger than one it recently showed in Japan and is the largest display of its type in the world, the company said.

Multi-touch screens differ from conventional touchpanels because they allow input from more than one spot on the screen so, for example, an image can be manipulated from opposite corners. Probably the most famous current example of the technology is the display on Apple's hit iPhone and iPod Touch devices.

With the technology helping to make the iPhone a smash hit display makers are now pursuing its inclusion in screens. The LG.Philips 52-inch screen uses an infrared image sensor to gauge input from fingers or other instruments and can recognize gestures such as the movement of fingers. It boasts full HD resolution (1,920 pixels by 1,080 pixels).

Additionally, the company will be showing an 84-inch multi-touch display that is made up of four 42-inch panels joined together.

LG.Philips LCD will also unveil a 47-inch "triple-view" screen. This has a filter over the front that sends light from pixels in one of three different directions so that three images can be displayed at once: one to viewers on the right of the screen, one to people in front of it and one to those on the left. The feature is being positioned at public display applications for use in advertising.

Also at CES the company will show a 47-inch double-sided screen that is made up of a single backlight sandwiched between two LCD panels and a 42-inch transreflective panel for outdoor advertising use.

International CES opens in Las Vegas on Jan. 7.

http://www.pcworld.com/article/id,140910-c,ces/article.html

Toshiba XF LCD TV's to get 100Hz

Most notable for an ultra slim profile of just 23mm the XF range of LCD TV's from Toshiba is also a very well equipped flat screen. From this March the 46in model in the XF series is set to become even more desirable with the addition of 100Hz processing.

Sporting a 10-bit panel for a broader range of colours and Full HD (1920 x 1080) resolution along with 3 HDMI as well as the usual component, Composite and S-video inputs, the XF series has certainly not relied on its good looks to make its way in the world.

Toshiba's ultra slim series of LCD TV's have gained a loyal following not only because of their looks but also for the successful implementation of innovative technology. Complementing Full HD, the XF series also includes an "Exact Scan" mode that allows a 1080i (such as Sky SD) broadcasted signal to be processed by the TV in the original broadcasted format, with no scaling of the original image.

The slim line nature of the Toshiba's XF series make the screens appear much smaller than they actually are, and the impact is that much greater, especially with HD material. With the forthcoming addition of 100Hz processing, the overall performance of these screens should improve, especially with Standard Definition material.

http://hdtvorg.co.uk/news/articles/2007123101.htm

Mitochondrial DNA

Mitochondrial DNA (some captions in German)

Mitochondrial DNA (mtDNA) is the DNA located in organelles called mitochondria. Most other DNA present in eukaryotic organisms is found in the cell nucleus. Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA being derived from the circular genomes of the bacteria that were engulfed by the early ancestors of today's eukaryotic cells. Each cell is estimated to contain 2-10 mtDNA copies.^[1] In the cells of extant organisms, the vast majority of the proteins present in the mitochondria (numbering approximately 1500 different types in mammals) are coded for by nuclear DNA, but the genes for some of them, if not most, are thought to have originally been of bacterial origin, having since been transferred to the eukaryotic nucleus during evolution. Among multicellular animals (metazoans), nearly all of the mtDNA in a fertilized egg (zygote) is inherited from only one parent - the female. One mechanism for this is simple dilution: an egg contains 100,000 to 1,000,000 mitochondria, whereas a sperm contains only 10 to 100. Another mechanism, documented for a few organisms, is that the sperm mitochondria do not enter the egg. Whatever the mechanism, this single parent (uniparental) pattern of mtDNA inheritance is found in most animals, most plants and in fungi as well.

In humans (and probably in metazoans in general), 100-10,000 separate copies of mtDNA are usually present per cell (egg and sperm cells are exceptions). In mammals, each circular mtDNA molecule consists of 15,000-17,000 base pairs, which encode the same 37 genes: 13 for proteins (polypeptides), 22 for transfer RNA (tRNA) and one each for the small and large subunits of ribosomal RNA (rRNA). This pattern is also seen among most metazoans, although in some cases one or more of the 37 genes is absent and the mtDNA size range is greater. Even greater variation in mtDNA gene content and size exists among fungi and plants, although there appears to be a core subset of genes that are present in all eukaryotes (except for the few that have no mitochondria at all). Some plant species have enormous mtDNAs (as many as 2,500,000 base pairs per mtDNA molecule!) but, surprisingly, even those huge mtDNAs contain the same number and kinds of genes as related plants with much smaller mtDNAs.

http://en.wikipedia.org/wiki/Mitochondrial_DNA

Mitochondrial genome

The mitochondrial genome is the genetic material of the mitochondria. The mitochondria are organelles that reproduce themselves semi-autonomously within eukaryotic cells.

The genetic material forming the mitochondrial genome is similar in structure to that of the prokaryotic genetic material. The mitochondrial chromosome is a circular DNA molecule, but unlike prokaryotes it is much smaller and several copies are present. This similarity supports the hypothesis that mitochondria arose from intracellular bacterial symbiotes, i.e. the endosymbiotic theory.

The mitochondria of a sexually-reproducing species are inherited maternally. In this way, mitochondrial genetic diseases can affect both males and females, but can only be transmitted by females to their offspring. The human mitochondrial genome consists of 16,569 base pairs, which encodes only 13 proteins, 22 tRNAs, and 2 rRNAs.

Compared to the nuclear genome, the mitochondrial genome possesses some very interesting features:

• All the genes are carried on a single circular DNA molecule.
• The genetic material is not bounded by a nuclear envelope.
• The DNA is not packed into chromatin.
• The genome contains little non-coding DNA ("junk" DNA, or introns).
• Some codons do not follow the universal rules in translation. Instead they resemble those of purple non-sulfur bacteria.
• Some bases are considered part of two different genes: both as the last base of one gene and as the first base of the next gene.

http://en.wikipedia.org/wiki/Mitochondrial_genome

Genome

In biology the genome of an organism is its whole hereditary information and is encoded in the DNA (or, for some viruses, RNA). This includes both the genes and the non-coding sequences of the DNA. The term was coined in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany, as a portmanteau of the words gene and chromosome.^[1]

More precisely, the genome of an organism is a complete DNA sequence of one set of chromosomes; for example, one of the two sets that a diploid individual carries in every somatic cell. The term genome can be applied specifically to mean the complete set of nuclear DNA (i.e., the "nuclear genome") but can also be applied to organelles that contain their own DNA, as with the mitochondrial genome or the chloroplast genome. When people say that the genome of a sexually reproducing species has been "sequenced," typically they are referring to a determination of the sequences of one set of autosomes and one of each type of sex chromosome, which together represent both of the possible sexes. Even in species that exist in only one sex, what is described as "a genome sequence" may be a composite from the chromosomes of various individuals. In general use, the phrase "genetic makeup" is sometimes used conversationally to mean the genome of a particular individual or organism. The study of the global properties of genomes of related organisms is usually referred to as genomics, which distinguishes it from genetics which generally studies the properties of single genes or groups of genes.

Both the number of base pairs and the number of genes vary widely from one species to another, and there is little connection between the two. At present, the highest known number of genes is around 60,000, for the protozoan causing trichomoniasis (see List of sequenced eukaryotic genomes), almost three times as many as in the human genome.

An analogy to the human genome is that of a book:

• The book is over one billion words long.
• The book is bound in 5,000 300 page volumes.
• The book fits into a cell nucleus the size of a pinpoint.
• A copy of the book (all 5000 volumes) is contained in every cell (except red blood cells) as a strand of DNA over two metres in length.

http://en.wikipedia.org/wiki/Genome