Category Archives: DNA

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Can A DNA Test Really Help You Lose Weight? Women's Health It seems as though a new diet hits the market every other week. Needless to say, wading through the endless sea of Whole30, high-protein, low-carb, and everything in between can be exhausting. But the reason we have all these endless options is because ...

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Can A DNA Test Really Help You Lose Weight? - Women's Health

A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA (dsDNA) but may also be single-stranded DNA (ssDNA). DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses. Single-stranded DNA is usually expanded to double-stranded in infected cells. Although Group VII viruses such as hepatitis B contain a DNA genome, they are not considered DNA viruses according to the Baltimore classification, but rather reverse transcribing viruses because they replicate through an RNA intermediate. Notable diseases like smallpox, herpes, and chickenpox are caused by such DNA viruses.

Genome organization within this group varies considerably. Some have circular genomes (Baculoviridae, Papovaviridae and Polydnaviridae) while others have linear genomes (Adenoviridae, Herpesviridae and some phages). Some families have circularly permuted linear genomes (phage T4 and some Iridoviridae). Others have linear genomes with covalently closed ends (Poxviridae and Phycodnaviridae).

A virus infecting archaea was first described in 1974. Several others have been described since: most have head-tail morphologies and linear double-stranded DNA genomes. Other morphologies have also been described: spindle shaped, rod shaped, filamentous, icosahedral and spherical. Additional morphological types may exist.

Orders within this group are defined on the basis of morphology rather than DNA sequence similarity. It is thought that morphology is more conserved in this group than sequence similarity or gene order which is extremely variable. Three orders and 31 families are currently recognised. A fourth orderMegaviralesfor the nucleocytoplasmic large DNA viruses has been proposed.[1] Four genera are recognised that have not yet been assigned a family.

Fifteen families are enveloped. These include all three families in the order Herpesvirales and the following families: Ascoviridae, Ampullaviridae, Asfarviridae, Baculoviridae, Fuselloviridae, Globuloviridae, Guttaviridae, Hytrosaviridae, Iridoviridae, Lipothrixviridae, Nimaviridae and Poxviridae.

Bacteriophages (viruses infecting bacteria) belonging to the families Tectiviridae and Corticoviridae have a lipid bilayer membrane inside the icosahedral protein capsid and the membrane surrounds the genome. The crenarchaeal virus Sulfolobus turreted icosahedral virus has a similar structure.

The genomes in this group vary considerably from ~10 kilobases to over 2.5 megabases in length. The largest bacteriophage known is Klebsiella Phage vB_KleM-RaK2 which has a genome of 346 kilobases.[2]

A recently proposed clade is the Megavirales which includes the nucleocytoplasmic large DNA viruses.[1][3] This proposal has yet to be ratified by the ICTV.

The virophages are a group of viruses that infect other viruses. Their classification has yet to be decided. A family Lavidaviridae has been proposed for the genera Mavirus and Sputnikvirus.[4]

A virus with a novel method of genome packing infecting species of the genus Sulfolobus has been described.[5] As this virus does not resemble any known virus it seems likely that a new family will be created for it.

Species of the order Caudovirales and of the families Corticoviridae and Tectiviridae infect bacteria.

Species of the order Ligamenvirales and the families Ampullaviridae, Bicaudaviridae, Clavaviridae, Fuselloviridae, Globuloviridae, Guttaviridae and Turriviridae infect hyperthermophilic archaea species of the Crenarchaeota.

Species of the order Herpesvirales and of the families Adenoviridae, Asfarviridae, Iridoviridae, Papillomaviridae, Polyomaviridae and Poxviridae infect vertebrates.

Species of the families Ascovirus, Baculovirus, Hytrosaviridae, Iridoviridae and Polydnaviruses and of the genus Nudivirus infect insects.

Species of the family Mimiviridae and the species Marseillevirus, Megavirus, Mavirus virophage and Sputnik virophage infect protozoa.

Species of the family Nimaviridae infect crustaceans.

Species of the family Phycodnaviridae and the species Organic Lake virophage infect algae. These are the only known dsDNA viruses that infect plants.

Species of the family Plasmaviridae infect species of the class Mollicutes.

Species of the family Pandoraviridae infect amoebae.

Species of the genus Dinodnavirus infect dinoflagellates. These are the only known viruses that infect dinoflagellates.

Species of the genus Rhizidiovirus infect stramenopiles. These are the only known dsDNA viruses that infect stramenopiles.

Species of the genus Salterprovirus and Sphaerolipoviridae infect species of the Euryarchaeota.

A group known as the pleolipoviruses, although having a similar genome organisation, differ in having either single or double stranded DNA genomes.[6] Within the double stranded forms have runs of single stranded DNA.[7] These viruses have been placed in the family Pleolipoviridae.[8] This family has been divided in three genera: Alphapleolipovirus, Betapleolipovirus and Gammapleolipovirus.

These viruses are nonlytic and form virions characterized by a lipid vesicle enclosing the genome.[9] They do not have nucleoproteins. The lipids in the viral membrane are unselectively acquired from host cell membranes. The virions contain two to three major structural proteins, which either are embedded in the membrane or form spikes distributed randomly on the external membrane surface.

This group includes the following viruses:

Although bacteriophages were first described in 1927, it was only in 1959 that Sinshemer working with phage Phi X 174 showed that they could possess single-stranded DNA genomes.[10][11] Despite this discovery until relatively recently it was believed that the majority of DNA viruses belonged to the double-stranded clade. Recent work suggests that this may not be the case with single-stranded viruses forming the majority of viruses found in sea water, fresh water, sediment, terrestrial, extreme, metazoan-associated and marine microbial mats.[12][13] Many of these "environmental" viruses belong to the family Microviridae.[14] However, the vast majority has yet to be classified and assigned to genera and higher taxa. Because most of these viruses do not appear to be related or are only distantly related to known viruses additional taxa will be created for these.

Although ~50 archaeal viruses are known, all but two have double stranded genomes. These two viruses have been placed in the families Pleolipoviridae and Spiraviridae

Families in this group have been assigned on the basis of the nature of the genome (circular or linear) and the host range. Ten families are currently recognised.

A division of the circular single stranded viruses into four types has been proposed.[15] This division seems likely to reflect their phylogenetic relationships.

Type I genomes are characterized by a small circular DNA genome (approximately 2-kb), with the Rep protein and the major open reading frame (ORF) in opposite orientations. This type is characteristic of the circoviruses, geminiviruses and nanoviruses.

Type II genomes have the unique feature of two separate Rep ORFs.

Type III genomes contain two major ORFs in the same orientation. This arrangement is typical of the anelloviruses.

Type IV genomes have the largest genomes of nearly 4-kb, with up to eight ORFs. This type of genome is found in the Inoviridae and the Microviridae.

Given the variety of single stranded viruses that have been described this schemeif it is accepted by the ICTVwill need to be extended.

The families Bidnaviridae and Parvoviridae have linear genomes while the other families have circular genomes. The Bidnaviridae have a two part genome and infect invertebrates. The Inoviridae and Microviridae infect bacteria; the Anelloviridae and Circoviridae infect animals (mammals and birds respectively); and the Geminiviridae and Nanoviridae infect plants. In both the Geminiviridae and Nanoviridae the genome is composed of more than a single chromosome. The Bacillariodnaviridae infect diatoms and have a unique genome: the major chromosome is circular (~6 kilobases in length): the minor chromosome is linear (~1 kilobase in length) and complementary to part of the major chromosome. Members of the Spiraviridae infect archaea. Members of the Genomoviridae infect fungi.

All viruses in this group require formation of a replicative forma double stranded DNA intermediatefor genome replication. This is normally created from the viral DNA with the assistance of the host's own DNA polymerase.

In the 9th edition of the viral taxonomy of the ICTV (published 2011) the Bombyx mori densovirus type 2 was placed in a new familythe Bidnaviridae on the basis of its genome structure and replication mechanism. This is currently the only member of this family but it seems likely that other species will be allocated to this family in the near future.

A new genus Bufavirus was proposed on the basis of the isolation of two new viruses from human stool.[16] Another member of this genusmegabat bufavius 1has been reported from bats.[17] The human viruses have since been renamed Primate protoparvovirus and been placed in the genus Protoparvovirus.[18][19]

The most recently introduced family of ssDNA viruses is the Genomoviridae (the family name is an acronym derived from geminivirus-like, no movement protein).[20]

The family includes 9 genera, namely Gemycircularvirus, Gemyduguivirus, Gemygorvirus, Gemykibivirus, Gemykolovirus, Gemykrogvirus, Gemykroznavirus, Gemytondvirus and Gemyvongvirus.[21]

The genus name Gemycircularvirus stands for Gemini-like myco-infecting circular virus.[22][23] the type species of the genus Gemycircularvirus - Sclerotinia sclerotiorum hypovirulence associated DNA virus 1 - is currently the only cultivated member of the family.[20] The rest of genomoviruses are uncultivated and have been discovered using metagenomics techniques.[21]

Isolates from this group have also been isolated from the cerebrospinal fluid and brains of patients with multiple sclerosis.[24]

A isolate from this group has also been identified in a child with encephalitis.[25]

Viruses from this group have also been isolated from the blood of HIV+ve patients.[26]

Ostrich faecal associated ssDNA virus has been placed in the genus Gemytondvirus. Rabbit faecal associated ssDNA virus has been placed in the genus Gemykroznavirus.

Another virus from this group has been isolated from mosquitoes.[27]

Ten new circular viruses have been isolated from dragonfly larvae.[28] The genomes range from 1628 to 2668 nucleotides in length. These dragonfly viruses have since been placed in the Gemycircularviridae.

Additional viruses from this group have been reported from dragonflies and damselflies.[29]

Three viruses in this group have been isolated from plants.[30]

A virus Cassava associated circular DNA virus that has some similarity to Sclerotinia sclerotiorum hypovirulence associated DNA virus 1 has been isolated.[31] This virus has been placed in the Gemycircularviridae.

Some of this group of viruses may infect fungi.[32]

A number of additional single stranded DNA viruses have been described but are as yet unclassified.

Viruses in this group have been isolated from other cases of encephalitis, diarrhoea and sewage.[33]

Two viruses have been isolated from human faeces circo-like virus Brazil hs1 and hs2 with genome lengths of 2526 and 2533 nucleotides respectively.[34] These viruses have four open reading frames. These viruses appear to be related to three viruses previously isolated from waste water, a bat and from a rodent.[35] This appears to belong to a novel group.

A novel species of virus - human respiratory-associated PSCV-5-like virus - has been isolated from the respiratory tract.[36] The virus is approximately 3 kilobases in length and has two open reading frames - one encoding the coat protein and the other the DNA replicase. The significance - if any - of this virus for human disease is unknown presently.

An unrelated group of ssDNA viruses, also discovered using viral metagenomics, includes the species bovine stool associated circular virus and chimpanzee stool associated circular virus.[37] The closest relations to this genus appear to be the Nanoviridae but further work will be needed to confirm this. Another isolate that appears to be related to these viruses has been isolated from pig faeces in New Zealand.[38] This isolate also appears to be related to the pig stool-associated single-stranded DNA virus. This virus has two large open reading frames one encoding the capsid gene and the other the Rep gene. These are bidirectionally transcribed and separated by intergenic regions. Another virus of this group has been reported again from pigs.[39] A virus from this group has been isolated from turkey faeces.[40] Another ten viruses from this group have been isolated from pig faeces.[41] Viruses that appear to belong to this group have been isolated from other mammals including cows, rodents, bats, badgers and foxes.[32]

Another virus in this group has been isolated from birds.[42]

Fur seal feces-associated circular DNA virus was isolated from the faeces of a fur seal (Arctocephalus forsteri) in New Zealand.[43] The genome has 2 main open reading frames and is 2925 nucleotides in length. Another virus - porcine stool associated virus 4[44] - has been isolated. It appears to be related to the fur seal virus.

Two viruses have been described from the nesting material yellow crowned parakeet (Cyanoramphus auriceps) Cyanoramphus nest-associated circular X virus (2308 nt) and Cyanoramphus nest-associated circular K virus (2087 nt)[45] Both viruses have two bidirectional open reading frames. Within these are the rolling-circle replication motifs I, II, III and the helicase motifs Walker A and Walker B. There is also a conserved nonanucleotide motif required for rolling-circle replication. CynNCKV has some similarity to the picobiliphyte nano-like virus (Picobiliphyte M5584-5)[46] and CynNCXV has some similarity to the rodent stool associated virus (RodSCV M-45).[47]

A virus with a circular genome sea turtle tornovirus 1 has been isolated from a sea turtle with fibropapillomatosis.[48] It is sufficiently unrelated to any other known virus that it may belong to a new family. The closest relations seem to be the Gyrovirinae. The proposed genus name for this virus is Tornovirus.

Among these are the parvovirus-like viruses. These have linear single-stranded DNA genomes but unlike the parvoviruses the genome is bipartate. This group includes Hepatopancreatic parvo-like virus and Lymphoidal parvo-like virus. A new family Bidensoviridae has been proposed for this group but this proposal has not been ratified by the ICTV to date.[49] Their closest relations appear to be the Brevidensoviruses (family Parvoviridae).[50]

A virus Acheta domesticus volvovirus - has been isolated from the house cricket (Acheta domesticus).[51] The genome is circular, has four open reading frames and is 2,517 nucleotides in length. It appears to be unrelated to previously described species. The genus name Volvovirus has been proposed for these species.[52] The genomes in this genus are ~2.5 nucleotides in length and encode 4 open reading frames.

Two new viruses have been isolated from the copepods Acartia tonsa and Labidocera aestiva Acartia tonsa copepod circo-like virus and Labidocera aestiva copepod circo-like virus respectively.

A virus has been isolated from the mud flat snail (Amphibola crenata).[53] This virus has a single stranded circular genome of 2351 nucleotides that encoded 2 open reading frames that are oriented in opposite directions. The smaller open reading frame (874 nucleotides) encodes a protein with similarities to the Rep (replication) proteins of circoviruses and plasmids. The larger open reading frame (955 nucleotides) has no homology to any currently known protein.

An unusual and as yet unnamed virus has been isolated from the flatwom Girardia tigrina.[54] Because of its genome organisation, this virus appears to belong to an entirely new family. It is the first virus to be isolated from a flatworm.

From the hepatopancreas of the shrimp (Farfantepenaeus duorarum) a circular single stranded DNA virus has been isolated.[55] This virus does not appear to cause disease in the shrimp.

A circo-like virus has been isolated from the shrimp (Penaeus monodon).[56] The 1,777-nucleotide genome is circular and single stranded. It has some similarity to the circoviruses and cycloviruses.

Ten viruses have been isolated from echinoderms.[57] All appear to belong to as yet undescribed genera.

A circular single stranded DNA virus has been isolated from a grapevine.[58] This species may be related to the family Geminiviridae but differs from this family in a number of important respects including genome size.

Several viruses baminivirus, nepavirus and niminivirus related to geminvirus have also been reported.[32]

A virus - Ancient caribou feces associated virus - has been cloned from 700-y-old caribou faeces.[59]

More than 600 single-stranded DNA viral genomes were identified in ssDNA purified from seawater .[60] These fell into 129 genetically distinct groups that had no recognizable similarity to each other or to other virus sequences, and thus many likely represent new families of viruses. Of the 129 groups, eleven were much more abundant than the others, and although their hosts have yet to be identified, they are likely to be eukaryotic phytoplankton, zooplankton and bacteria.

A virus Boiling Springs Lake virus appears to have evolved by a recombination event between a DNA virus (circovirus) and an RNA virus (tombusvirus).[61] The genome is circular and encodes two proteinsa Rep protein and a capsid protein.

Further reports of viruses that appear to have evolved from recombination events between ssRNA and ssDNA viruses have been made.[62]

A new virus has been isolated from the diatom Chaetoceros setoensis.[63] It has a single stranded DNA genome and does not appear to be a member of any previously described group.

A virus - FLIP (Flavobacterium-infecting, lipid-containing phage) - has been isolated from a lake.[64] This virus has a circular ssDNA genome (9,174 nucleotides) and an internal lipid membrane enclosed in a icosahedral capsid. The capsid organisation is he capsid organization pseudo T = 21 dextro. The major capsid protein has two -barrels. The capsid organisation is similar to bacteriophage PM2 - a double stranded bacterial virus.

Satellite viruses are small viruses with either RNA or DNA as their genomic material that require another virus to replicate. There are two types of DNA satellite virusesthe alphasatellites and the betasatellitesboth of which are dependent on begomoviruses. At present satellite viruses are not classified into genera or higher taxa.

Alphasatellites are small circular single strand DNA viruses that require a begomovirus for transmission. Betasatellites are small linear single stranded DNA viruses that require a begomovirus to replicate.

Phylogenetic relationships between these families are difficult to determine. The genomes differ significantly in size and organisation. Most studies that have attempted to determine these relationships are based either on some of the more conserved proteinsDNA polymerase and othersor on common structural features. In general most of the proposed relationships are tentative and have not yet been used by the ICTV in their classification.

While determining the phylogenetic relations between the various known clades of viruses is difficult, on a number of grounds the herpesviruses and caudoviruses appear to be related.

While the three families in the order Herpesvirales are clearly related on morphological grounds, it has proven difficult to determine the dates of divergence between them because of the lack of gene conservation.[65] On morphological grounds they appear to be related to the bacteriophagesspecifically the Caudoviruses.

The branching order among the herpesviruses suggests that Alloherpesviridae is the basal clade and that Herpesviridae and Malacoherpesviridae are sister clades.[66] Given the phylogenetic distances between vertebrates and molluscs this suggests that herpesviruses were initially fish viruses and that they have evolved with their hosts to infect other vertebrates.

The vertebrate herpesviruses initially evolved ~400 million years ago and underwent subsequent evolution on the supercontinent Pangaea.[67] The alphaherpesvirinae separated from the branch leading to the betaherpesvirinae and gammaherpesvirinae about 180 million years ago to 220 million years ago.[68] The avian herpes viruses diverged from the branch leading to the mammalian species.[69] The mammalian species divided into two branchesthe Simplexvirus and Varicellovirus genera. This latter divergence appears to have occurred around the time of the mammalian radiation.

Several dsDNA bacteriophages and the herpesviruses encode a powerful ATP driven DNA translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The critical components of the packaging machine are the packaging enzyme (terminase) which acts as the motor and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex consists of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase) and cuts viral genome concatemers. It forms a motor complex containing five large terminase subunits. The terminase-viral DNA complex docks on the portal vertex. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. Only a single gene encoding the putative ATPase subunit of the terminase (UL15) is conserved among all herpesviruses. To a lesser extent this gene is also found in T4-like bacteriophages suggesting a common ancestor for these two groups of viruses.[70] Another paper has also suggested that herpesviruses originated among the bacteriophages.[71]

A common origin for the herpesviruses and the caudoviruses has been suggested on the basis of parallels in their capsid assembly pathways and similarities between their portal complexes, through which DNA enters the capsid.[72] These two groups of viruses share a distinctive 12-fold arrangement of subunits in the portal complex. A second paper has suggested an evolutionary relationship between these two groups of viruses.[71]

It seems likely that the tailed viruses infecting the archaea are also related to the tailed viruses infecting bacteria.[73][74]

The nucleocytoplasmic large DNA virus group (Asfarviridae, Iridoviridae, Marseilleviridae, Mimiviridae, Phycodnaviridae and Poxviridae) along with three other familiesAdenoviridae, Cortiviridae and Tectiviridae and the phage Sulfolobus turreted icosahedral virus and the satellite virus Sputnik all possess double -barrel major capsid proteins suggesting a common origin.[75]

Several studies have suggested that the family Ascoviridae evolved from the Iridoviridae.[76][77][78][79] A study of the Iridoviruses suggests that the Iridoviridae, Ascoviridae and Marseilleviridaeare are related with Ascoviruses most closely related to Iridoviruses.[80]

The family Polydnaviridae may have evolved from the Ascoviridae.[81] Molecular evidence suggests that the Phycodnaviridae may have evolved from the family Iridoviridae.[82] These four families (Ascoviridae, Iridoviridae, Phycodnaviridae and Polydnaviridae) may form a clade but more work is needed to confirm this.

Some of the relations among the large viruses have been established.[83] Mimiviruses are distantly related to Phycodnaviridae. Pandoraviruses share a common ancestor with Coccolithoviruses within the Phycodnaviridae family.[84] Pithoviruses are related to Iridoviridae and Marseilleviridae.

Based on the genome organisation and DNA replication mechanism it seems that phylogenetic relationships may exist between the rudiviruses (Rudiviridae) and the large eukaryal DNA viruses: the African swine fever virus (Asfarviridae), Chlorella viruses (Phycodnaviridae) and poxviruses (Poxviridae).[85]

Based on the analysis of the DNA polymerase the genus Dinodnavirus may be a member of the family Asfarviridae.[86] Further work on this virus will required before a final assignment can be made.

Based on the analysis of the coat protein, Sulfolobus turreted icosahedral virus may share a common ancestry with the Tectiviridae.

The families Adenoviridae and Tectiviridae appear to be related structurally.[87]

Baculoviruses evolved from the nudiviruses 310 million years ago.[88][89]

The Hytrosaviridae are related to the baculoviruses and to a lesser extent the nudiviruses suggesting they may have evolved from the baculoviruses.[90]

The Nimaviridae may be related to nudiviruses and baculoviruses.[91]

The Nudiviruses seem to be related to the polydnaviruses.[92]

A protein common to the families Bicaudaviridae, Lipotrixviridae and Rudiviridae and the unclassified virus Sulfolobus turreted icosahedral virus is known suggesting a common origin.[93]

Examination of the pol genes that encode the DNA dependent DNA polymerase in various groups of viruses suggests a number of possible evolutionary relationships.[94] All know viral DNA polymerases belong to the DNA pol families A and B. All possess a 3'-5'-exonuclease domain with three sequence motifs Exo I, Exo II and Exo III. The families A and B are distinguishable with family A Pol sharing 9 distinct consensus sequences and only two of them are convincingly homologous to sequence motif B of family B. The putative sequence motifs A, B, and C of the polymerase domain are located near the C-terminus in family A Pol and more central in family B Pol.

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DNA virus - Wikipedia

NEW YORK -- At Jef Boeke's lab, you can whiff an odor that seems out of place, as if they were baking bread here.

But he and his colleagues are cooking up something else altogether: yeast that works with chunks of man-made DNA.

Scientists have long been able to make specific changes in the DNA code. Now, they're taking the more radical step of starting over, and building redesigned life forms from scratch. Boeke, a researcher at New York University, directs an international team of 11 labs on four continents working to "rewrite" the yeast genome, following a detailed plan they published in March.

Their work is part of a bold and controversial pursuit aimed at creating custom-made DNA codes to be inserted into living cells to change how they function, or even provide a treatment for diseases. It could also someday help give scientists the profound and unsettling ability to create entirely new organisms.

The genome is the entire genetic code of a living thing. Learning how to make one from scratch, Boeke said, means "you really can construct something that's completely new."

The research may reveal basic, hidden rules that govern the structure and functioning of genomes. But it also opens the door to life with new and useful characteristics, like microbes or mammal cells that are better than current ones at pumping out medications in pharmaceutical factories, or new vaccines. The right modifications might make yeast efficiently produce new biofuels, Boeke says.

Some scientists look further into the future and see things like trees that purify water supplies and plants that detect explosives at airports and shopping malls.

Also on the horizon is redesigning human DNA. That's not to make genetically altered people, scientists stress. Instead, the synthetic DNA would be put into cells, to make them better at pumping out pharmaceutical proteins, for example, or perhaps to engineer stem cells as a safer source of lab-grown tissue and organs for transplanting into patients.

Some have found the idea of remaking human DNA disconcerting, and scientists plan to get guidance from ethicists and the public before they try it.

Still, redesigning DNA is alarming to some. Laurie Zoloth of Northwestern University, a bioethicist who's been following the effort, is concerned about making organisms with "properties we cannot fully know." And the work would disturb people who believe creating life from scratch would give humans unwarranted power, she said.

"It is not only a science project," Zoloth said in an email. "It is an ethical and moral and theological proposal of significant proportions."

Rewritten DNA has already been put to work in viruses and bacteria. Australian scientists recently announced that they'd built the genome of the Zika virus in a lab, for example, to better understand it and get clues for new treatments.

At Harvard University, Jeffrey Way and Pamela Silver are working toward developing a harmless strain of salmonella to use as a vaccine against food poisoning from salmonella and E. coli, as well as the diarrhea-causing disease called shigella.

A key goal is to prevent the strain from turning harmful as a result of picking up DNA from other bacteria. That requires changing its genome in 30,000 places.

"The only practical way to do that," Way says, "is to synthesize it from scratch."

The cutting edge for redesigning a genome, though, is yeast. Its genome is bigger and more complex than the viral and bacterial codes altered so far. But it's well-understood and yeast will readily swap man-made DNA for its own.

Still, rewriting the yeast genome is a huge job.

It's like a chain with 12 million chemical links, known by the letters, A, C, G and T. That's less than one-hundredth the size of the human genome, which has 3.2 billion links. But it's still such a big job that Boeke's lab and scientists in the United States, Australia, China, Singapore, and the United Kingdom are splitting up the work. By the time the new yeast genome is completed, researchers will have added, deleted or altered about a million DNA letters.

Boeke compares a genome to a book with many chapters, and researchers are coming out with a new edition, with chapters that allow the book to do something it couldn't do before.

To redesign a particular stretch of yeast DNA, scientists begin with its sequence of code letters - nature's own recipe. They load that sequence into a computer, then tell the computer to make specific kinds of changes. For example one change might let them rearrange the order of genes, which might reveal strategies to make yeast grow better, says NYU researcher Leslie Mitchell.

Once the changes are made, the new sequence used as a blueprint. It is sent to a company that builds chunks of DNA containing the new sequence. Then these short chunks are joined together in the lab to build ever longer strands.

The project has so far reported building about one-third of the yeast genome. Boeke hopes the rest of the construction will be done by the end of the year. But he says it will take longer to test the new DNA and fix problems, and to finally combine the various chunks into a complete synthetic genome.

Last year, Boeke and others announced a separate effort, what is now called Genome Project-write or GP-write . It is chiefly focused on cutting the cost of building and testing large genomes, including human ones, by more than 1,000-fold within 10 years. The project is still seeking funding.

In the meantime, leaders of GP-write have started discussions of ethical, legal and social issues. And they realize the idea of making a human genome is a sensitive one.

"The notion that we could actually write a human genome is simultaneously thrilling to some and not so thrilling to others," Boeke said. "So we recognize this is going to take a lot of discussion."

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Scientists build DNA from scratch to alter life's blueprint - CBS News

A 63-year-old man serving a life sentence for the 1988 murder of a Lincoln woman has won a push to get new DNA testing on previously untested evidence that he thinks could clear him of the crime.

Herman Buckman has served more than 29 years for the first-degree murder of Denise Strawkowski. He is at the Nebraska State Penitentiary.

On Feb. 19, 1988, she was found dead in the front seat of her car in a ravine near U.S. 34 and Northwest 48th Street. Strawkowski had been shot twice in the head.

At a trial, prosecutors said Buckman had killed her over a drug debt. The Lancaster County jury found him guilty.

Last September, Buckman filed a motion for forensic DNA testing of biological material asking that testing be done on the victim's underwear, as well as the floor mat and steering wheel cover.

Buckman contends that the testing could point to someone else as her killer.

He said the state never tested the evidence before and that the floor mats and steering wheel cover hadn't shown up on an earlier inventory.

In an order late last week, Lancaster County District Judge Susan Strong sustained the motion over an objection by the County Attorney's office. And she appointed the Commission on Public Advocacy to represent Buckman.

It's not the first time Buckman has filed a petition under the DNA Testing Act, which enables convicted people to request DNA testing at state expense if it could lead to a new trial or to outright exoneration.

In 2004, he lost his bid for a new trial after testing on cigarette butts found at the crime scene were inconclusive.

At best, Buckman could neither be included or excluded as being a contributor of some of the genetic material found on the tested cigarettes, according to the Nebraska Supreme Court opinion.

In 2001, Buckman petitioned the Lancaster County District Court for DNA testing on bloodied clothing belonging to him, and on cigarette butts found in the back seat of the car in which Stawkowski was murdered.

A judge approved the testing, but the examination of the clothing found no blood traces to test; and testing on the cigarette butts was inconclusive, partly because of contamination during storage.

At the 1988 trial, an expert witness for the state testified the butts had blood substances consistent with Buckman's blood type.

The later tests found DNA from more than one person, one of whom could have been Buckman.

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Judge OKs DNA testing in 1988 Lincoln murder case - Lincoln Journal Star

BERKELEY A DNA match has led to a first-degree murder charge in a 2012 beating death in Berkeley.

Kavion L. Thomas, 27, was charged Tuesday with beating Patti Ann Harvill to death April 25, 2012, in her Berkeley home.

Charges say Thomas DNA was found on Harvills body and in droplets of blood at her home in the 9000 block of Harold Drive.

She was found in a hallway; police found no evidence of a break-in, and no valuables were taken.

Thomas is serving an eight-year sentence in Kentucky for manslaughter in the October 2014 beating death of a man at a closed-down car wash in Lexington, Ky.

News reports say he and two others were accused of killing Brian DePreta, 50. Records show Thomas became eligible for parole for that conviction on July 1.

Harvills sister said Tuesday she is relieved about the charges but says she is still frustrated, particularly with Berkeley police, that a resolution has taken more than five years.

Once they didnt get a hit on DNA, they sat back and waited for (the killer) to mess up, said Harvills sister, Gina Giardina, of Park Hills, Mo. I thought I was going to go to my grave not knowing who killed her.

Police have said they think Harvill knew her killer, but Giardina said her sister did not know Thomas.

Harvills family has held annual vigils near Harvills home seeking clues in her murder. Giardina said she can now finish her forearm tattoo of a cross with her sisters name and date of death. She plans to have Rest in Peace inked above the cross.

Harvill was divorced, had lived in Berkeley since 2003 and worked as a receptionist for the Skypark garage near St. Louis Lambert International Airport.

Bail for Thomas on the murder charge was set at $500,000.

Joel Currier 314-621-5804 @joelcurrier on Twitter jcurrier@post-dispatch.com

Excerpt from:
DNA match leads to charges in woman's 2012 beating death in her Berkeley home - STLtoday.com

He will seek the job permanently.

Danny Monteverde, WWLTV 5:21 PM. CDT July 25, 2017

Joe Lopinto

GRETNA -- Former state Rep. Joe Lopinto will, at least on an interim basis, helm the Jefferson Parish Sheriffs Office once Jefferson Parish Sheriff Newell Normand steps down Aug. 31 to take on a role as a host on WWL Radio.

And though the soft spoken married father of two will assume a high-profile role, he is far from a household name and will have six months to introduce himself to the citizens of the parish as possible political jockeying begins to replace Normand.

It wont be much of a sell, those who know him say.

The son of a veteran New Orleans police officer, he was a JPSO deputy and detective for eight years while he put himself through law school at Loyola University. He later was elected to the state House of Representatives, where he represented the Metairie area and served as chairman of the Committee on the Administration of Criminal Justice.

Its in his DNA -- law enforcement, said Clancy DuBos, WWL-TV political analyst and Gambit columnist.

Lopinto announced last May he would resign from the Legislature, before his term was over, to take on a job as in-house counsel to the Sheriffs Office, a post he held until recently when Normand named him chief deputy.

Speculation in political circles at the time of Lopinto's departure from the Legislature was that Normand was grooming him has his hand-picked successor.

During his time in Baton Rouge, Lopinto, a Republican, developed a reputation as a hard worker but was ousted from his chairmanship since he crossed party lines to endorse John Bel Edwards for governor and voted for Rep. Walt Leger, D-New Orleans, to be the House speaker.

State Sen. Danny Martiny, R-Kenner, described Lopinto as practical during his time in the Legislature.

He was one of four people I thought were really going to make a difference when his class took over, said Martiny, who is seeking a seat on the Jefferson Parish council.

Martiny described Lopinto as an up and comer whose low-key demeanor disguises an effective leader.

Since Normand is retiring, state statute dictates his number two step in as an interim sheriff. An election will be held next spring.

DuBos said its unlikely a large field will challenge Lopinto once the campaign for sheriff starts, thanks largely to Normands support. Well know in the next couple of weeks.

Normand, for his part, wasnt known much outside of the JPSO before he was named interim sheriff after Harry Lees death in October 2007, but that did little to hinder his chances at landing the job permanently -- also thanks to Lees endorsement before he died.

Normand was swept into office with 91 percent of the vote in November 2007 and won reelection in 2011 with 92 percent of the vote and 88 percent in 2015.

Having only learned Sunday that Normand was retiring and he would replace him, Lopinto said hes not yet focused on a campaign but will seek the job on a permanent basis.

The citizens of Jefferson Parish will have to look at me and my resume and determine who they think is the best person, he said. I know during the interim I have a job to do.

2017 WWL-TV

The rest is here:
Lopinto has law enforcement 'in his DNA' - WWL

NEW YORK DAILY NEWS

Tuesday, July 25, 2017, 8:13 PM

A DNA match helped police catch the suspect in the attempted rape of a Bronx clothing store clerk nearly two years ago, police sources said.

Cops on Tuesday arrested Oumar Fofana, accusing him of cornering a 41-year-old woman inside the South Bronx store on Aug. 1, 2015.

He walked into the store which police have not named, to protect the womans identity at about 1:30 p.m. and browsed the clothes on the rack before he attacked, cops said.

The woman fought him off, and he took off, police said.

DNA match yields conviction for fraudsters 1998 subway rape

The 20-year-old is charged with attempted rape and sexual abuse.

Fofana, who sources said has eight prior arrests, was out on $5,000 bail after a June bust for weapon possession in the Bronx. Sources said police had his DNA in a database following one of his arrests.

Last July, authorities said, he got into Enterprise rental car a Dodge Challenger without permission at JFK Airport, then crashed it into a wall.

He pleaded guilty to misdemeanor criminal mischief in February and received a conditional discharge.Fofana awaits arraignment in Bronx Criminal Court.

NYC expands controversial DNA testing on seized guns

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DNA helped cops nab suspect in attempted rape of Bronx store clerk - New York Daily News

July 25, 2017 by Marieke Oudelaar, Oxford Science Blog Abstract illustration of self-interacting domains and their boundaries. Hanssen and colleagues show that removal of such boundaries extends the self interacting domains to include other genes which are inappropriately activated. Credit: Oxford Science Blog

Our bodies are composed of trillions of cells, each with its own job. Cells in our stomach help digest our food, while cells in our eyes detect light, and our immune cells kill off bugs. To be able to perform these specific jobs, every cell needs a different set of tools, which are formed by the collection of proteins that a cell produces. The instructions for these proteins are written in the approximately 20,000 genes in our DNA.

Despite all these different functions and the need for different tools, all our cells contain the exact same DNA sequence. But one central question remains unanswered how does a cell know which combination of the 20,000 genes it should activate to produce its specific toolkit?

The answer to this question may be found in the pieces of DNA that lie between our protein-producing genes. Although our cells contain a lot of DNA, only a small part of this is actually composed of genes. We don't really understand the function of most of this other sequence, but we do know that some of it has a function in regulating the activity of genes. An important class of such regulatory DNA sequences are the enhancers, which act as switches that can turn genes on in the cells where they are required.

However, we still don't understand how these enhancers know which genes should be activated in which cells. It is becoming clear that the way DNA is folded inside the cell is a crucial factor, as enhancers need to be able to interact physically with genes in order to activate them. It is important to realise that our cells contain an enormous amount of DNA approximately two meters! which is compacted in a very complex structure to allow it to fit into our tiny cells. The long strings of DNA are folded into domains, which cluster together to form larger domains, creating an intricate hierarchical structure. This domain organisation prevents DNA from tangling together like it would if it were an unwound ball of wool, and allows specific domains to be unwound and used when they are needed.

Researchers have identified key proteins that appear to define and help organise this domain structure. One such protein is called CTCF, which sticks to a specific sequence of DNA that is frequently found at the boundaries of these domains. To explore the function of these CTCF boundaries in more detail and to investigate what role they may play in connecting enhancers to the right genes, our team studied the domain that contains the -globin genes, which produce the haemoglobin that our red blood cells use to circulate oxygen in our bodies.

Firstly, as expected from CTCF's role in defining boundaries, we showed that CTCF boundaries help organise the -globin genes into a specific domain structure within red blood cells. This allows the enhancers to physically interact with and switch on the -globin genes in this specific cell type. We then used the gene editing technology of CRISPR/Cas9 to snip out the DNA sequences that normally bind CTCF, and found that the boundaries in these edited cells become blurred and the domain loses its specific shape. The -globin enhancers now not only activate the -globin genes, but cross the domain boundaries and switch on genes in the neighbouring domain.

This study provides new insights into the contribution of CTCF in helping define these domain boundaries to help organise our DNA and restrict the regulation of gene activity within the cells where it is needed. This is an important finding that could explain the misregulation of gene activity that contributes to many diseases. For example in cancer, mutations of these boundary sequences in our DNA could lead to inappropriate activation of the genes that drive tumour growth.

The full study, 'Tissue-specific CTCFcohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo', can be read in the journal Nature Cell Biology.

Explore further: New study helps solve a great mystery in the organization of our DNA

More information: Lars L. P. Hanssen et al. Tissue-specific CTCFcohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo, Nature Cell Biology (2017). DOI: 10.1038/ncb3573

After decades of research aiming to understand how DNA is organized in human cells, scientists at the Gladstone Institutes have shed new light on this mysterious field by discovering how a key protein helps control gene organization.

It seems like a feat of magic. Human DNA, if stretched out into one, long spaghetti-like strand, would measure 2 meters (six feet) long. And yet, all of our DNA is compacted more than 10,000 times to fit inside a single cell. ...

Twenty years ago, the protein complex cohesin was first described by researchers at the IMP. They found that its shape strikingly corresponds to its function: when a cell divides, the ring-shaped structure of cohesin keeps ...

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have discovered that the transcriptional regulator CTCF plays an essential role in antibody production. The study, led by Dr. Almudena ...

Within almost every human cell is a nucleus six microns in diameterabout one 300th of a human hair's widththat is filled with roughly three meters of DNA. As the instructions for all cell processes, the DNA must be ...

In cells, DNA is transcribed into RNAs that provide the molecular recipe for cells to make proteins. Most of the genome is transcribed into RNA, but only a small proportion of RNAs are actually from the protein-coding regions ...

Researchers from Monash University's Biomedicine Discovery Institute have helped solve the mystery of how emus became flightless, identifying a gene involved in the development and evolution of bird wings.

Researchers at the University of California San Diego have found that microbial species living on cheese have transferred thousands of genes between each other. They also identified regional hotspots where such exchanges ...

A team of scientists from the Kunming Institute of Botany in China and the Max Planck Institute for Chemical Ecology in Jena has discovered that parasitic plants of the genus Cuscuta (dodder) not only deplete nutrients from ...

Our bodies are composed of trillions of cells, each with its own job. Cells in our stomach help digest our food, while cells in our eyes detect light, and our immune cells kill off bugs. To be able to perform these specific ...

Humpback whales learn songs in segments like the verses of a human song and can remix them, a new study involving University of Queensland research has found.

New research from Australia and Sweden has shown how a dragonfly's brain anticipates the movement of its prey, enabling it to hunt successfully. This knowledge could lead to innovations in fields such as robot vision.

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Breaking boundaries in our DNA - Phys.Org

July 25, 2017 Credit: Cancer Research UK

Inhibitors of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) kill BRCA-deficient tumours, and have significant activity in single agent and combination therapy. Professor Herbie Newell, of Newcastle University (with Hilary Calvert, Nicola Curtin, Barbara Durkacz, Bernard Golding, Roger Griffin and Ruth Plummer), was part of the team responsible for making the PARP inhibitor rucaparib.

In December 2016, the FDA fast-tracked rucaparib (Rubraca) into the clinic to treat women with advanced ovarian cancer who have received two or more prior chemotherapies and whose tumours have a BRCA gene mutation. Here Herbie explains the start of the story.

"In the late 1980s, temozolomide, a DNA-methylating agent, was the drug of the moment. We reasoned that a PARP inhibitor should make temozolomide, as well as some other drugs and ionising radiation, more active by inhibiting DNA repair. There was lots of scepticism from pharma as they said a PARP inhibitor wouldn't be a standalone drug and would increase toxicity; consequently there was no major commercial interest. Nevertheless, in a collaboration between the Cancer Research Unit and the School of Chemistry, we established a drug discovery group in Newcastle in 1990 to make and test PARP inhibitors. Rucaparib was subsequently identified in collaboration with Agouron and Pfizer GRD, and is now being developed and marketed by Clovis Oncology.

The critical breakthrough for PARP inhibitors was the recognition of single agent activity in cells defective for homologous recombination repair, as found in BRCA-deficient tumours (reported independently in Nature in 2005 by two UK teams). With the help of the CRUK Centre for Drug Development, rucaparib went into phase 1 trials in 2003, and went on to stimulate high levels of commercial interest in PARP inhibitors in multiple companies. The FDA approved rucaparib in December 2016, having previously identified it as a breakthrough drug."

In 2003, Professor Ruth Plummer, now the chair of the New Agents Committee, wrote the prescription for the first patient in the world to be treated by rucaparib, the first ever cancer patient to be treated by a PARP inhibitor. "It was always clear we had a drug that did something. We have some patients whose scans are currently clear and have been for some years now. It's fantastic really great. The patient from our first trial doesn't even come to clinic now he's been discharged!"

Susan Ross: a patient's perspective on rucaparib

Susan Ross from Whitley Bay in Tyne and Wear was first diagnosed with ovarian cancer with a BRCA gene mutation 10 years ago. Here Susan explains her experience of being part of a clinical trial of rucaparib (Rubraca) at the Northern Centre for Cancer Care in Newcastle.

"Early in 2015 I was told the ovarian cancer had returned and unfortunately an operation was not possible. I was facing the prospect of having chemotherapy again. Previously I had had three rounds of chemotherapy as well as four operations, so knowing what treatment was going to entail, my heart sank. I thought 'Can I go through this again?' and 'Do I really want to go through this again?'

My consultant organised a BRCA gene mutation test, which showed I was a BRCA2 mutation carrier. I was then offered the opportunity to go on a clinical trial of this new treatment rucaparib, and I grabbed it with both hands.

My care is overseen by Dr Yvette Drew, and I attend the unit every three weeks to be monitored, and discuss any worries with the nurses and doctors. I've been taking rucaparib as part of this trial since December 2015 and it's the best I've felt in 10 years, both physically and mentally. With the help and support of all the staff, it feels like I've got my life back.

Being part of a clinical trial means I'm monitored very closely. I am so thankful for all those who have been involved in the development of rucaparib and for making this clinical trial possible. Being part of a clinical trial is an opportunity to help make a difference, help cancer patients in the future and hopefully find a cure for this awful disease. I'd do it again in an instant."

Explore further: Ovarian cancer patients get access to life-extending drug

Journal reference: Nature

Provided by: Cancer Research UK

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Rucaparibtargeting DNA repair and a patient's perpective - Medical Xpress

Recently, a DNA test appeared with a premise so far-fetched that its fate was profane and merciless ridicule. Soccer Genomics offers personalized, DNA-based training regimens to young players, and its goofy ad went viral amid internet outrage. It is, alas, only the most recent example of the growing field of sometimes-dubious lifestyle DNA tests.

Its a jungle out there, says Eric Topol, a genomicist at the Scripps Research Institute. As DNA sequencing has gotten cheaper, a number of small companies have looked to fill niches around the two big consumer DNA-testing behemoths, 23andMe and AncestryDNA. These newer tests usually dont offer disease-risk information, which would bring the scrutiny of the FDA, but they skirt the boundaries by focusing on nutrition and fitness. Sometimes, they just aim for fun, like a DNA test for wine preferences. Ive likened these lifestyle tests to horoscopesvague, occasionally informative, sometimes amusing.

The DNA Test as Horoscope

Into this jungle now comes a new player with an impressive pedigree. Helix is a new venture from private equity firms and Illumina, the company that makes most of the DNA-sequencing machines in the United States. 23andMe and AncestryDNA use Illuminas machines, as do most research labs. On Monday, after two years of anticipation since the initial announcement, Helix officially launched a marketplace for products based on DNA tests.

Helix has an innovative business model. Most DNA-testing companies only look for a set number of variants in DNA. Helix sequences all of the expressed genes in the bodya technique called whole-exome sequencing. This is very expensive, but Helix subsidizes most of the cost aside from one-time $80 sequencing fee. Then, it has third-party developers create products focused on specific genetic information. The products available now include everything from a National Geographic ancestry test, to personalized diet coaching, to a custom DNA-based scarf. You pay for each individual product, and the prices range from under $100 to a couple hundred.

The companys CEO, Robin Thurston, likens Helix to the Apple app store, which is a very deliberate comparison. Unlike Google, which takes a fairly hands-off approach to apps in the Google Play store, Apple individually reviews every app. Helix has a 14-person team that reviews the science behind each of the products they feature, too, which is how the company plans to differentiate itself from the world of pseudoscientific DNA tests. Hopefully it will translate into us telling consumers that being on the Helix platform is different, says Thurston. You can trust Helix in the long run. (Just to be clear, Soccer Genomics has nothing to do with Helix.)

Oleksandr Savsunenko, the CEO of Titanovo, whose DNA Diet Coach product was slated to be sold on the Helix platform, gave me a rundown of Helixs scientific review process. He says his company had originally submitted 200 scientific studies to back up the recommendations in their product60 to 70 percent of which did not meet Helixs standards. That includes a 68-person study that an earlier version of Titanovos product used to recommend cloudy apple juice for fat loss. Of course I was disappointed when they started to say this is bad, this is bad, this is bad, but in the end the product we have obtained is really strong, says Savsunenko. Titanovo is now discontinuing the earlier product, called DNA Lifestyle Coach, to focus exclusively on its DNA Diet Coach product through Helix.

(Sometime after the interview with Savsunenko, a Helix spokesperson said DNA Diet Coach would no longer be included in Mondays marketplace launch: Titanovos beta testing identified some areas that need fine-tuning before broad release and hence decided to hold off launching on Monday.)

Products currently available through Helix have gotten criticism though, especially a DNA test for wine preference, made by a company called Vinome. The gist of the skepticism goes like this: DNA can tell you what a person can taste, but it cant really tell you if that person will like it. Thurston says he thinks Vinome meets their scientific standard because the company makes clear that their taste algorithm is based on more than DNA. Vinome also uses an questionnaire, and sure, that can get at your personal taste preferences.

At that point, though, how much value is the DNA test itself adding? Even when there is solid evidence linking a gene to a predisposition, the relationship is probabilistic. Its more like you are 30 percent more likely to grow blue hair than you will definitely grow blue hair. Genes and the environment interact to affect health outcomes. At least some of the products on Helixs platform seem to resolve this ambiguity by basing advice on things that have nothing to do with DNA.

Another partner, EverlyWell, sells a number of tests for proteins and fats in the blood and breast milk. It is now selling through Helix a plus version of its food-sensitivity, metabolism, and breast-milk tests that also looks at DNA. If you already have the blood test that reveals what your body is doing now, whats the additional value of the DNA test that reveals what your body could potentially be doing?

My perspective is that genetic data is valuable to give you a baseline, says EverlyWells CEO, Julia Cheek. She points out that someone who has low magnesium levels might want to know they have a predisposition to low magnesium so they can adjust their diet. Alternatively, one or two low magnesium tests might prompt the same diet adjustments.

On one hand, this strategy of integrating DNA tests with other sources of information allows Helixs partners to hew closer to the established science of genetics. On the other, DNA sequencing is obviously the real draw of Helixs marketplace, and whole exome sequencing is orders of magnitude more expensive than a questionnaire or blood test.

Topol, who follows genomic medicine closely, is skeptical that current direct-to-consumer DNA tests have much utility for healthy people. Helix was created to help Illumina sell more DNA-sequencing machines by growing the space for consumer tests. And if these new tests dont actually demonstrate the value of DNA sequencing, Topol says it could lead to backlash. It could lead to a lesser opinion of genomics, he says. Im afraid of that as well.

Since Helix was announced in 2015 to fanfare and a $100 million investment, its unusual business model has been the subject of much speculation. Now its marketplace is finally here, and you can decide for yourself.

Excerpt from:
How Do You Know When a DNA Test Is BS? - The Atlantic