document_title: Rudolph the Red-Nosed Reindeer (TV special)

question_text: who narrated the christmas tv special rudolph the red-nosed reindeer

text: Plot[edit]

text: Sam the Snowman welcomes the viewers to Christmastown at the North Pole and introduces Santa and Mrs. Claus who live in a castle located north of the Christmas Tree Forest. Mrs. Claus fusses over Santa as she wants him to fatten up by Christmas Eve. Sam then recalls the year Christmas was almost cancelled due to a snowstorm and tells the story of how a very special reindeer saved the day.

text: Donner, Santa's lead reindeer, and his wife have given birth to their new baby fawn, Rudolph. Upon admiring him, they are surprised to see that Rudolph has been born with a glowing red nose. When Santa arrives, he warns Donner that Rudolph will not make the sleigh team because of his nose. Donner then decides to hide the nose by covering it with mud to allow Rudolph to fit in with all the other reindeer.

text: Over Rudolph's first year of life, Donner trains him in the basics of being a reindeer, including hiding from the Abominable Snow Monster of the North. Rudolph enters the reindeer games, competing against his fellow fawns and befriends a young buck named Fireball. During flight practice, Rudolph meets a doe named Clarice who tells him he is cute, and kisses him, which causes an elated Rudolph to fly higher and faster than everyone else. However, while celebrating with Fireball, Rudolph's nose cover pops off, and Fireball and the others react with fear, then scorn and finally rejection as Comet expels Rudolph from the Reindeer Games. Walking away, Rudolph walks with Clarice, who supports him, until her father firmly tells her to never have any more contact with a red-nosed reindeer. Then, Rudolph meets up with Hermey, an elf who ran away from Santa's workshop because he wanted to be a dentist instead of making toys, and they decide to run away together. The pair then meet a prospector named Yukon Cornelius, who has fruitlessly searched his whole life for silver and gold. After escaping the snow monster on an ice floe, the trio crash land on the Island of Misfit Toys where unloved or unwanted toys live with their ruler, a winged lion named King Moonracer. The king allows the group to stay one night on the island in exchange for returning to Christmastown to ask Santa to find homes for the unwanted toys. However, Rudolph leaves the island in the middle of the night on his own, fearing that his nose, which attracts the snow monster, will endanger his friends.

text: Time goes by and Rudolph grows into adulthood; he tries and fails to find a place to settle where he will be accepted despite his nose and eventually decides to return home. There, he finds that Fireball continues to bully him and that his parents and Clarice have been out looking for him for months; he sets out once again to find them, only to discover that the snow monster has captured them. Rudolph tries to save Clarice and his parents, but the monster hits him in the head with a stalactite, knocking him unconscious. Hermey and Yukon arrive, and discovering Rudolph's plight, they hatch a plan to save him: Hermey lures the monster out of his cave by posing as a pig, Yukon drops rocks on his head to knock him out, and Hermey then pulls out all the monster's teeth. When the monster awakens, it has also lost its confidence, and Yukon effortlessly scares the beast off a cliff, himself falling off with his pack of dogs in the process. Mourning Yukon's presumed death, Rudolph, Hermey, Clarice, and the Donners return home. After hearing the group's story, everyone apologizes to Rudolph and Hermey for their mistreatment, and Santa welcomes them back to Christmastown, promising that he will find homes for the Misfit Toys; in addition, Hermey opens his own dentist's office, and Clarice's father apologizes for being so hard on Rudolph. Yukon then returns and shows the wary Christmastown residents that the now-tamed snow monster can be useful by having it trim a Christmas tree. Santa interrupts the celebration, grimly informing everyone that because of the storm, he is forced to cancel the Christmas trip. Santa is soon distracted by Rudolph's red nose and realizes that its light could cut through the storm. He asks Rudolph to lead the sleigh and Rudolph agrees. The team then flies off to the island and pick up the toys. The special ends with Santa wishing the viewers a merry Christmas as he and Rudolph fly off into the night.

text: Cast[edit]

text:
Billie Mae Richards[3][4] voices Rudolph, a reindeer of formidable acumen (he learns to speak shortly after birth) and physical strength who is shunned for his nonconforming red nose, but later saves Christmas.
Stan Francis voices:

Santa Claus, portrayed in the special as a moody, nervous and "skinny Santa" whose fears are only allayed when he conjures the idea of using Rudolph's nose to lead the sleigh.
King Moonracer, a winged lion who rules the entire Island of Misfit Toys. King Moonracer's voice uses a reverb effect to distinguish it from Santa Claus.

Paul Kligman voices:

Donner, Rudolph's father and Santa's most prized reindeer. While he loves and accepts Rudolph, he shows great concern that society will reject him for his nose and tries to protect him by creating a nose cover.
Comet, head coach of the Reindeer Games.
Clarice's unnamed father, who forbids Clarice from shaming the family by associating with a red-nosed reindeer.

Burl Ives voices Sam the Snowman, the narrator.
Paul Soles voices Hermey, an elf who dreams of pursuing a career in dentistry and "feels different" from the other elves. He eventually is forced out and runs off with Rudolph.
Janis Orenstein voices Clarice, a female reindeer who is the only one of Rudolph's age to not reject him. She later joins Rudolph's parents in the search party.
Larry D. Mann voices Yukon Cornelius, the "greatest prospector of the North" who joins Rudolph and Hermey on their journey but never finds the silver and gold he seeks.
Peg Dixon voices:

Mrs. Claus, a pushy wife who mocks her husband's lack of appetite.
Mrs. Donner, a loving and mostly submissive wife.

Carl Banas voices:

The Head Elf. For the Head Elf's voice, Banas uses a meek Bill Thompson-like voice when speaking in front of Santa Claus, but turns into a ruthless boss with a voice similar to Mel Blanc's Yosemite Sam or Cosmo Spacely when Santa is not around.
Various Misfit Toys, including a Spotted Elephant, King Moonracer's footman; a bird that swims, a cowboy who rides an ostrich, a train with square wheels on his caboose, two teddy bears (one on a bicycle and one with wings), a boat that doesn't float, a set of clown nesting dolls with a wind-up mouse as the last one, a water pistol that shoots jelly, a plane that can't fly, a toy car that only drives in reverse, and a scooter with two wheels in front and one in back.

Alfie Scopp voices:

Fireball, who introduces Rudolph to the opposite sex, but later snubs Rudolph when his red nose is revealed.
Charlie-In-The-Box, the island's sentry.

Corinne Conley voices Dolly, a seemingly normal girl rag doll on the Island of Misfit Toys. Her misfit problem is never explained on the special; many decades later, on NPR's Wait Wait… Don't Tell Me! news quiz show (broadcast December 8, 2007), Rudolph's producer, Arthur Rankin Jr., noted that Dolly's problem was psychological, caused by being abandoned by her owner (named as Sue in the special) and suffering depression from feeling uncared-for.[5]

text: Production[edit]

text: The TV special, with the teleplay by Romeo Muller, introduced several new characters inspired by the song's lyrics. Muller told an interviewer shortly before his death that he would have preferred to base the teleplay on May's original book, but could not find a copy.[6] Other than Burl Ives, all characters were portrayed by Canadian actors recorded at RCA studios in Toronto under the supervision of Bernard Cowan.[7]

text: After the script, concept designs and storyboards for Rudolph were done by Arthur Rankin, Jr. and his staff of artists at Rankin/Bass in New York City. The company's trademark stop motion animation process, known as "Animagic", was filmed at MOM Productions in Tokyo with supervision by Tadahito Mochinaga and associate direction by Kizo Nagashima.[6] Besides Rudolph, Mochinaga and the rest of the Japanese puppet animation staff are also known for their partnership with Rankin/Bass on their other Animagic productions almost throughout the 1960s, from The New Adventures of Pinocchio, to Willy McBean and his Magic Machine, to The Daydreamer and Mad Monster Party?.[6]

text: Aftermath[edit]

text: Since those involved with the production had no idea of the future value of the stop-motion puppet figures used in the production, many were not preserved. Rankin claimed in 2007 to be in possession of an original Rudolph figure.[8] Nine other puppets—including Santa and young Rudolph—were given to a secretary, who gave them to family members. Eventually seven were discarded.[8] In 2005, the remaining two puppets of Rudolph and Santa were appraised on Antiques Roadshow; the episode aired in 2006 on PBS. At that time, their appraised value was between $8,000 and $10,000. The puppets had been damaged through years of rough handling by children and storage in an attic.[9] Toy aficionado Kevin Kriess bought Santa and Rudolph in 2005; in 2007, he had both puppets restored by Screen Novelties, a Los Angeles-based collective of film directors specializing in stop motion animation with puppet fabricator Robin Walsh leading the project.[8][10] The figures have been shown at conventions since then.[11]

text: Production credits[edit]

text:
Directed by Larry Roemer
Produced by Arthur Rankin, Jr.
Co-Producer: Jules Bass
Written by Romeo Muller
Adapted from the Story by Robert L. May
Adapted from the Song by Johnny Marks
Music and Lyrics by Johnny Marks
Music Conducted and Arranged by Maury Laws
Associate Director: Kizo Nagashima
Recording Engineers: Bill Giles, Alan Mirchin, Ralph Friedman
Sound Effects: Walter Gustafson
Recording Supervisor: Bernard Cowan
"Animagic" Supervisor: Tadahito Mochinaga (aka Tad Mochinaga)
Continuity Design: Anthony Peters

text: Different versions[edit]

text: Original 1964 NBC broadcast edit[edit]

text: This version has the NBC "living color" peacock at the introduction. It includes the original end credits, where an elf drops presents that list all the technical credits. It also includes commercials that were exclusively for GE small appliances with some of the same animated elves from the main program introducing each of the products, and closing NBC network bumpers, including promos for the following week's episodes of GE College Bowl and Meet the Press, which were presumably pre-empted that Sunday for the inaugural 5:30 PM (EST) telecast. The College Bowl quiz show was also sponsored by GE.[12] The original does not include Santa traveling to the Island of Misfit Toys, but does include a scene near the end of the special in which Yukon Cornelius discovers a peppermint mine near Santa's workshop. He can be seen throughout the special tossing his pickax into the air, sniffing, then licking the end that contacts the snow or ice. Deletion of the peppermint segment in 1965, to make room for Santa traveling to the Island of Misfit Toys, leaves audience to assume that Cornelius was attempting to find either silver or gold by taste alone.[6]

text: 1965–1997 telecasts[edit]

text: The 1965 broadcast also included a new duet between Rudolph and Hermey called "Fame and Fortune", which replaced a scene in which the same characters sang "We're a Couple of Misfits". Viewers of the 1964 special complained that Santa was not shown fulfilling his promise to the Misfit Toys (to include them in his annual toy delivery).[6] In reaction, a new scene for subsequent rebroadcasts was produced with Santa making his first stop at the Island to pick up the toys. This is the ending that has been shown on all telecasts and video releases ever since. Until sometime in the 1970s the special aired without additional cuts, but eventually more commercial time was required by the network. In 1978, several sequences were deleted to make room for more advertising: the instrumental bridge from "We Are Santa's Elves" featuring the elf orchestra, additional dialogue by Burl Ives, and the "Peppermint Mine" scene resolving the fate of Yukon Cornelius.[6] The special's 1993 restoration saw "Misfits" returned to its original film context, and the 2004 DVD release showcases "Fame and Fortune" as a separate musical number.

text: 1998– CBS telecasts[edit]

text: Most of the 1965 deletions were restored in 1998, and "Fame and Fortune" was replaced with the original "We're a Couple of Misfits" reprise. A short slide reading "Rankin/Bass Presents" was inserted at the beginning of the special to reflect the company's name change. The "Peppermint Mine" scene was not restored; it has not aired on CBS since the mid 70s.

text: Starting in 2005, CBS aired the video of the "Fame and Fortune" scene with the soundtrack replaced by an edited version of "We're a Couple of Misfits".[6] The special has been edited to make more time for commercial advertising by shortening some musical numbers.

text: Home media[edit]

text: When Rudolph was first issued on VHS, Betamax, and LaserDisc by Family Home Entertainment and Broadway Video from 1989 to 1997 under the Christmas Classics Series label, the 1965 rebroadcast print described above was used. All current video prints of Rudolph by Classic Media are a compendium of the two previous telecast versions of the special. All the footage in the current versions follow the original NBC airing (without the original GE commercials) up until the "Peppermint Mine" scene, followed by the final act of the 1965 edit (with the Island of Misfit Toys finale and the 1965 alternate credits in place of the original end credit sequence).

text: In 1998, the special was released by Sony Wonder on VHS. In 2000, it was released on DVD, and on Blu-ray Disc in 2010 (although the Blu-ray does not contain the bonus features from the previous DVD release.) This edit has been made available in original color form by former rights holders Classic Media,[13] (which in 2012 became the DreamWorks Classics division of DreamWorks Animation, and finally in 2016, part of Universal Pictures)[14] As previously mentioned, this is also the version currently airing on CBS, albeit in edited form to accommodate more commercial time. In November 2014, Classic Media released a 50th anniversary edition of the special on Blu-ray.[15] Walmart released an exclusive 50th anniversary Blu-ray edition with a storybook.

text: Soundtrack[edit]

text: The songs and incidental music were all written by Johnny Marks, with Maury Laws supervising. In addition to the songs previously mentioned, the score also includes the film's love theme "There's Always Tomorrow", sung by Clarice after Rudolph is kicked out of the reindeer games. Marks' holiday standard "Rockin' Around the Christmas Tree" appears as instrumental background music when Rudolph first arrives at the Reindeer Games. Also included in the soundtrack is an instrumental version of Marks' setting of the Christmas hymn "I Heard the Bells on Christmas Day."

text: In 1964, an LP record of the soundtrack was released on Decca Records. It contained all the original songs performed as they are in the special, with the exception of Burl Ives' material, which has been re-recorded. MCA Special Products released the soundtrack on CD in June 1995. It is an exact duplication of the original LP released in 1964. Tracks 1-9 are the original soundtrack selections while tracks 10-19 are the same songs performed by the Decca Concert Orchestra. The song "Fame and Fortune" is not contained on either release. On November 30, 2004 the soundtrack was certified Gold by the Recording Industry Association of America for selling over 500,000 copies.

text: Ives re-recorded "Rudolph the Red-Nosed Reindeer" and "A Holly Jolly Christmas", with different arrangements, for his own album Have a Holly Jolly Christmas in 1965.[16]

text: Merchandise[edit]

text: Books and other items related to the show have in some cases misspelled "Hermey" as "Herbie". Rich Goldschmidt, who wrote Rudolph the Red-Nosed Reindeer: The Making of the Rankin/Bass Holiday Classic, says the scripts by Romeo Muller show the spelling to be "Hermey".[17]

text: A Rudolph the Red-Nosed Reindeer video game was released on November 9, 2010. The adaptation was published by Red Wagon Games for the Wii and Nintendo DS, and was developed by High Voltage Software and Glyphic Entertainment respectively. The Wii version was received poorly, and garnered extremely negative reviews from sites such as IGN giving it a 1.5/10.[18]

text: Reception[edit]

text: Rudolph the Red-Nosed Reindeer received an approval rating of 92% on review aggregator website Rotten Tomatoes, based on thirteen reviews.[19]

text: Sequels[edit]

text: The Rankin/Bass special, which currently airs on CBS, inspired numerous television sequels made by the same studio:

text:
Rudolph's Shiny New Year (1976), a special that first aired on ABC and is still aired annually on both ABC and Freeform.
Rudolph and Frosty's Christmas in July (1979), a feature-length special that paired Rudolph with the song-inspired character Frosty the Snowman.
Rudolph the Red-Nosed Reindeer and the Island of Misfit Toys (2001), a direct-to-video computer-animated film that is considered[by whom?] an unofficial sequel to the 1964 film.
"Rudolph the Red-Nosed Reindeer - 4D Attraction"[20] (2016), A faithful, 10-minute stop motion story adaptation in the form of a 4D film for SimEx-Iwerks;[21] produced by Bent Image Lab and directed by Chel White.

text: In popular culture[edit]

text: The television special's familiarity to American audiences through its annual rebroadcasts, along with its primitive stop-motion animation that is easy to recreate with modern technology and the special's ambiguous copyright status, has lent itself to numerous parodies and homages over the years.

text: Films by Corky Quakenbush[edit]

text: Animator Corky Quakenbush has produced parodies of Rudolph for several American television shows:

text:
In its December 16, 1995 episode, the Fox Network's comedy series MADtv aired "Raging Rudolph",[22] which also parodied Martin Scorsese's films. In it, Sam The Snowman narrates in a Joe Pesci-like voice how Rudolph and Hermey got violent Mafia-style revenge on their tormentors. This was followed by two sequels: "The Reinfather",[23] spoofing The Godfather trilogy and "A Pack of Gifts Now",[24] spoofing Apocalypse Now.
A 2001 episode of That '70s Show, titled "An Eric Forman Christmas", featured a subplot where Kelso was taunted by his friends for still watching "kiddie shows" like Rudolph even though he was in high school. A dream sequence produced and directed by Quakenbush, Kelso himself appears in stop-motion form with Rudolph and Santa who encourage him to continue watching their show.
In December 2005, the George Lopez Show featured an animated segment in which Lopez sees a stop-motion version of himself on television in a Rudolph-style special mirroring the theme of the holiday episode.
In the stop-motion animated film The Nightmare Before Christmas (1993), Jack looks through a book version of Rudolph the Red Nosed Reindeer to find a logical answer to explain Christmas to the other citizens of Halloween Town. Later, Zero, the ghost dog, has a magnificently glowing pumpkin nose, which is bright enough to break through the fog that Sally has conjured up. Jack lets Zero go to the head of his skeleton reindeer team and light the way for him.
Chel White, of Bent Image Lab, directed two parodies that played on Saturday Night Live', on Robert Smigel's TV Funhouse:

In a 2001 TV Funhouse episode, Sam the Snowman refuses to narrate the story because of the September 11, 2001 attacks. He then takes two children to Ground Zero at New York City, but Santa Claus convinces him to narrate the story, because people need comforting stories like Rudolph the Red-Nosed Reindeer. Sam decided to narrate the tale, but was immediately interrupted by a special news report.
In 2004, TV Funhouse referenced the Red state-blue state divide. In the segment, Santa hangs out with liberal celebrities Natalie Merchant, Margaret Cho, Al Franken, and Moby while skipping over the Red states ("screw the red states, voting for that dumbass president just because of that moral values crap. I don't want any part of them!"). Rudolph's red nose turns blue.

In 2004, for Rudolph the Red-Nosed Reindeer's 40th anniversary, CBS produced stop motion promos for their programming line-up, done in the style of Rankin/Bass animation. Appearing as elves in the CBS promos were puppet versions of CBS stars Jeff Probst from Survivor, Ray Romano and Doris Roberts from Everybody Loves Raymond, William Petersen and Marg Helgenberger from CSI, Charlie Sheen from Two and a Half Men, Phil Simms and Greg Gumbel from The NFL on CBS, and late-night talk show host David Letterman. A new stop-motion animation featuring Rudolph and Santa meeting even more CBS network stars was also aired in 2005.
Mystery Science Theater 3000 made numerous references to the special in their movie hecklings, such as Rudolph's line "I'm cute!! I'm cuute!! She said I'm cuuuuuutte!!!!". In episode 321, which screened Santa Claus Conquers the Martians, the MST3K cast had their own ideas for potential residents on the Island of Misfit Toys including Toaster Dolls, Patrick Swayze's Roadhouse board game, the EZ Bake Foundry, and Mr. Mashed Potato Head.
In 2010, the comedy website CollegeHumor made a short parody video called "Rudolph The Regular Reindeer", depicting what the special would've been like if Rudolph had a normal nose.

text: Uses in advertising[edit]

text:
In 1964, Rankin & Bass produced several commercials for the General Electric-sponsored broadcast.[12]
In November 2007, the Aflac insurance company released a commercial that featured Rudolph, who has a cold but does not want to miss work. All his friends say he will be unable to pay for his expenses. Santa then tells them about Aflac. Charlie wonders what will happen if Rudolph is not better by Christmas, but Rudolph thinks the Aflac duck can do the work. Rudolph gets better in a week, but Blitzen is sick, so the Aflac duck fills in for him.[25]
In 2009, Verizon began showing a commercial of the Misfit Toys with an AT&T phone. The characters wonder why it is there with all of its features but soon discover why, when the phone shows a map of where it has 3G coverage. (Verizon's ad campaign touts its much wider 3G coverage compared to AT&T's.) The toy airplane replies: "You're gonna fit right in here!" and falls on the ground laughing.[citation needed]
Starting in 2011, there have been several Bing.com commercials, filmed to look like the same stop-motion style as the special, which feature several characters including Rudolph, Yukon Cornelius, Hermey, the Bumble, and the Misfit Toys.[citation needed]
A 2012 commercial for Windows phone features Bumble the Abominable Snowman (with his full set of teeth), speed-dating and getting advice from friends through Live Tiles. A follow-up features Bumble at Santa's North Pole pool party, and Santa using Live Tiles on his new Windows Phone to help him give his elves the holiday-season toy production directives.[citation needed]
A 2013 commercial for Nissan shows a woman in a dealership briefly entering a fantasy, wherein Santa's Elves, including Boss Elf and Hermey, have expanded their manufacturing line to include Nissan cars. Furthermore, the Bumble makes an appearance test driving one to his obvious approval.[citation needed]
CBS celebrated the special's 50th anniversary in 2014 with Rudolph and Sam the Snowman celebrating with cast members from The Big Bang Theory and NCIS while passing by their studio lots.[citation needed]
In 2014, the United States Postal Service used four characters (Rudolph, Hermey, Yukon Cornelius, and Bumble) for the year's "Contemporary Christmas" stamp issue.[2][26]
In 2015, the Rudolph characters began appearing in commercials for AT&T with a stop-motion version of spokes-character Lily Adams.

text: Other References[edit]

text: In the sci-fi/comedy series The Orville, in the episode "About a Girl", characters watch Rudolph to make the character Bortus consider his plans to arrange gender reassignment surgery for his newborn daughter (Bortus's species, the Moclans, are a single-gender species who statistically produce only one female every seventy-five years, with females thus having no clear place in their society) by demonstrating how unconventional people can accomplish great things, although Bortus humorously misinterprets the film to suggest that Rudolph's father might have considered euthanizing his child as an anomaly.

text: Copyright issues[edit]

text: The copyright of the Rudolph the Red-Nosed Reindeer special lies in an area of uncertainty in regard to American federal copyright law. When the recording was originally published, the date of copyright (published in Roman numerals) was accidentally listed as 1164 (MCLXIV), omitting an M that should have been present (1964 in Roman numerals is MCMLXIV); this mistake was not corrected with subsequent edits and remains on televised prints to this day.[27] The songs were validly and separately copyrighted, and the original character on which the special was based also remains under copyright and trademark protection, extending some indirect copyright protection to the special as a derivative work. (A number of films, such as It's a Wonderful Life and His Girl Friday, fall under similar circumstances: a public domain film loosely based on a copyrighted work.)

text: Assuming the error in the copyright is considered substantial enough to invalidate it (U.S. copyright law before 1988 required works to have a valid date on a copyright notice, while providing some leeway in regard to non-substantial errors), the error puts large portions of the special not directly tied to the songs or original story into the public domain. (Some of the characters, particularly Santa Claus and the adult reindeer, relied on material that was already public domain anyway; all of the characters except Rudolph, most of the images, and large portions of the spoken soundtrack would thus be public domain in this interpretation.) Because of the indirect copyright protections and uncertainty over their extent, permission is still required to show the program as a whole. The extensive derivative works seen in popular culture are likely a byproduct of this uncertain copyright status.


document_title: Genetics

question_text: when did modern study of genetics begin and with whom

root

text: Genetics

text: Etymology[edit]

text: The word genetics stems from the ancient Greek γενετικός genetikos meaning "genitive"/"generative", which in turn derives from γένεσις genesis meaning "origin".[3][4][5]

tag: p

text: History[edit]

text: The observation that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding.[6] The modern science of genetics, seeking to understand this process, began with the work of the Augustinian friar Gregor Mendel in the mid-19th century.[7]

text: Prior to Mendel, Imre Festetics, a Hungarian noble, who lived in Kőszeg before Mendel, was the first who used the word "genetics." He described several rules of genetic inheritance in his work The genetic law of the Nature (Die genetische Gesätze der Natur, 1819). His second law is the same as what Mendel published. In his third law, he developed the basic principles of mutation (he can be considered a forerunner of Hugo de Vries).[8]

text: Other theories of inheritance preceded his work. A popular theory during Mendel's time was the concept of blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents.[9] Mendel's work provided examples where traits were definitely not blended after hybridization, showing that traits are produced by combinations of distinct genes rather than a continuous blend. Blending of traits in the progeny is now explained by the action of multiple genes with quantitative effects. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children,[10] although evidence in the field of epigenetics has revived some aspects of Lamarck's theory.[11] Other theories included the pangenesis of Charles Darwin (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.[12]

text: Mendelian and classical genetics[edit]

text: Modern genetics started with Mendel's studies of the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brünn, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically.[13] Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.

text: The importance of Mendel's work did not gain wide understanding until 1900, after his death, when Hugo de Vries and other scientists rediscovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905[14][15] (the adjective genetic, derived from the Greek word genesis—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860[16]). Bateson both acted as a mentor and was aided significantly by the work of female scientists from Newnham College at Cambridge, specifically the work of Becky Saunders, Nora Darwin Barlow, and Muriel Wheldale Onslow.[17] Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London in 1906.[18]

text: After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1911, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.[19] In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.[20]

text: Molecular genetics[edit]

text: Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA, and scientists did not know which of the two is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation (see Griffith's experiment): dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, the Avery–MacLeod–McCarty experiment identified DNA as the molecule responsible for transformation.[21] The role of the nucleus as the repository of genetic information in eukaryotes had been established by Hämmerling in 1943 in his work on the single celled alga Acetabularia.[22] The Hershey–Chase experiment in 1952 confirmed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.[23]

text: James Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA has a helical structure (i.e., shaped like a corkscrew).[24][25] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what look like rungs on a twisted ladder.[26] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for replication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand. This property is what gives DNA its semi-conservative nature where one strand of new DNA is from an original parent strand.[27]

text: Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of protein production.[28] It was discovered that the cell uses DNA as a template to create matching messenger RNA, molecules with nucleotides very similar to DNA. The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide sequences and amino acid sequences is known as the genetic code.[29]

text: With the newfound molecular understanding of inheritance came an explosion of research.[30] A notable theory arose from Tomoko Ohta in 1973 with her amendment to the neutral theory of molecular evolution through publishing the nearly neutral theory of molecular evolution. In this theory, Ohta stressed the importance of natural selection and the environment to the rate at which genetic evolution occurs.[31] One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger. This technology allows scientists to read the nucleotide sequence of a DNA molecule.[32] In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of DNA from a mixture.[33] The efforts of the Human Genome Project, Department of Energy, NIH, and parallel private efforts by Celera Genomics led to the sequencing of the human genome in 2003.[34][35]

text: Features of inheritance[edit]

text: Discrete inheritance and Mendel's laws[edit]

text: At its most fundamental level, inheritance in organisms occurs by passing discrete heritable units, called genes, from parents to offspring.[36] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.[13][37] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white—but never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles.

text: In the case of the pea, which is a diploid species, each individual plant has two copies of each gene, one copy inherited from each parent.[38] Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene are called homozygous at that gene locus, while organisms with two different alleles of a given gene are called heterozygous.

text: The set of alleles for a given organism is called its genotype, while the observable traits of the organism are called its phenotype. When organisms are heterozygous at a gene, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.[39]

text: When a pair of organisms reproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known as Mendel's first law or the Law of Segregation.

text: Notation and diagrams[edit]

text: Geneticists use diagrams and symbols to describe inheritance. A gene is represented by one or a few letters. Often a "+" symbol is used to mark the usual, non-mutant allele for a gene.[40]

text: In fertilization and breeding experiments (and especially when discussing Mendel's laws) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is the Punnett square.

text: When studying human genetic diseases, geneticists often use pedigree charts to represent the inheritance of traits.[41] These charts map the inheritance of a trait in a family tree.

text: Multiple gene interactions[edit]

text: Organisms have thousands of genes, and in sexually reproducing organisms these genes generally assort independently of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law" or the "law of independent assortment," means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)

text: Often different genes can interact in a way that influences the same trait. In the Blue-eyed Mary (Omphalodes verna), for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all or are white. When a plant has two copies of this white allele, its flowers are white—regardless of whether the first gene has blue or magenta alleles. This interaction between genes is called epistasis, with the second gene epistatic to the first.[42]

text: Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height and skin color). These complex traits are products of many genes.[43] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is called heritability.[44] Measurement of the heritability of a trait is relative—in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a trait with complex causes. It has a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.[45]

text: Molecular basis for inheritance[edit]

text: DNA and chromosomes[edit]

text: The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[46] Viruses are the only exception to this rule—sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material.[47] Viruses cannot reproduce without a host and are unaffected by many genetic processes, so tend not to be considered living organisms.

text: DNA normally exists as a double-stranded molecule, coiled into the shape of a double helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.[48]

text: Genes are arranged linearly along long chains of DNA base-pair sequences. In bacteria, each cell usually contains a single circular genophore, while eukaryotic organisms (such as plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.[49] The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes, chromatin is usually composed of nucleosomes, segments of DNA wound around cores of histone proteins.[50] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome.

text: While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene.[38] The two alleles for a gene are located on identical loci of the two homologous chromosomes, each allele inherited from a different parent.

text: Many species have so-called sex chromosomes that determine the gender of each organism.[51] In humans and many other animals, the Y chromosome contains the gene that triggers the development of the specifically male characteristics. In evolution, this chromosome has lost most of its content and also most of its genes, while the X chromosome is similar to the other chromosomes and contains many genes. The X and Y chromosomes form a strongly heterogeneous pair.

text: Reproduction[edit]

text: When cells divide, their full genome is copied and each daughter cell inherits one copy. This process, called mitosis, is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that are genetically identical to their parents are called clones.

text: Eukaryotic organisms often use sexual reproduction to generate offspring that contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction alternates between forms that contain single copies of the genome (haploid) and double copies (diploid).[38] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell gametes such as sperm or eggs.

text: Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.[52] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known as transformation.[53] These processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated.

text: Recombination and genetic linkage[edit]

text: The diploid nature of chromosomes allows for genes on different chromosomes to assort independently or be separated from their homologous pair during sexual reproduction wherein haploid gametes are formed. In this way new combinations of genes can occur in the offspring of a mating pair. Genes on the same chromosome would theoretically never recombine. However, they do, via the cellular process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[54] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid cells.

text: The first cytological demonstration of crossing over was performed by Harriet Creighton and Barbara McClintock in 1931. Their research and experiments on corn provided cytological evidence for the genetic theory that linked genes on paired chromosomes do in fact exchange places from one homolog to the other.[55]

text: The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between the points. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated.[56] For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage; alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear linkage map that roughly describes the arrangement of the genes along the chromosome.[57]

text: Gene expression[edit]

text: Genetic code[edit]

text: Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell. Proteins are made up of one or more polypeptide chains, each of which is composed of a sequence of amino acids, and the DNA sequence of a gene (through an RNA intermediate) is used to produce a specific amino acid sequence. This process begins with the production of an RNA molecule with a sequence matching the gene's DNA sequence, a process called transcription.

text: This messenger RNA molecule is then used to produce a corresponding amino acid sequence through a process called translation. Each group of three nucleotides in the sequence, called a codon, corresponds either to one of the twenty possible amino acids in a protein or an instruction to end the amino acid sequence; this correspondence is called the genetic code.[58] The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but it never transfers from protein back into the sequence of DNA—a phenomenon Francis Crick called the central dogma of molecular biology.[59]

text: The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions.[60][61] Some are simple structural molecules, like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as enzymes by facilitating chemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein hemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.

text: A single nucleotide difference within DNA can cause a change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, sickle-cell anemia is a human genetic disease that results from a single base difference within the coding region for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.[62] Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease.

text: Some DNA sequences are transcribed into RNA but are not translated into protein products—such RNA molecules are called non-coding RNA. In some cases, these products fold into structures which are involved in critical cell functions (e.g. ribosomal RNA and transfer RNA). RNA can also have regulatory effects through hybridization interactions with other RNA molecules (e.g. microRNA).

text: Nature and nurture[edit]

text: Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotypes an organism displays. The phrase "nature and nurture" refers to this complementary relationship. The phenotype of an organism depends on the interaction of genes and the environment. An interesting example is the coat coloration of the Siamese cat. In this case, the body temperature of the cat plays the role of the environment. The cat's genes code for dark hair, thus the hair-producing cells in the cat make cellular proteins resulting in dark hair. But these dark hair-producing proteins are sensitive to temperature (i.e. have a mutation causing temperature-sensitivity) and denature in higher-temperature environments, failing to produce dark-hair pigment in areas where the cat has a higher body temperature. In a low-temperature environment, however, the protein's structure is stable and produces dark-hair pigment normally. The protein remains functional in areas of skin that are colder—such as its legs, ears, tail and face—so the cat has dark-hair at its extremities.[63]

text: Environment plays a major role in effects of the human genetic disease phenylketonuria.[64] The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive intellectual disability and seizures. However, if someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, they remain normal and healthy.

text: A common method for determining how genes and environment ("nature and nurture") contribute to a phenotype involves studying identical and fraternal twins, or other siblings of multiple births.[65] Because identical siblings come from the same zygote, they are genetically the same. Fraternal twins are as genetically different from one another as normal siblings. By comparing how often a certain disorder occurs in a pair of identical twins to how often it occurs in a pair of fraternal twins, scientists can determine whether that disorder is caused by genetic or postnatal environmental factors – whether it has "nature" or "nurture" causes. One famous example involved the study of the Genain quadruplets, who were identical quadruplets all diagnosed with schizophrenia.[66] However such tests cannot separate genetic factors from environmental factors affecting fetal development.

text: Gene regulation[edit]

text: The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. Transcription factors are regulatory proteins that bind to DNA, either promoting or inhibiting the transcription of a gene.[67] Within the genome of Escherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid tryptophan. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genes—tryptophan molecules bind to the tryptophan repressor (a transcription factor), changing the repressor's structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating negative feedback regulation of the tryptophan synthesis process.[68]

text: Differences in gene expression are especially clear within multicellular organisms, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into variant cell types in response to external and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.

text: Within eukaryotes, there exist structural features of chromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.[69] These features are called "epigenetic" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types grown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of paramutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.[70]

text: Genetic change[edit]

text: Mutations[edit]

text: During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can affect the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.[71][72] Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure.[73] Chemical damage to DNA occurs naturally as well and cells use DNA repair mechanisms to repair mismatches and breaks. The repair does not, however, always restore the original sequence.

text: In organisms that use chromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations.[74] Errors in crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequence – duplications, inversions, deletions of entire regions – or the accidental exchange of whole parts of sequences between different chromosomes (chromosomal translocation).

text: Natural selection and evolution[edit]

text: Mutations alter an organism's genotype and occasionally this causes different phenotypes to appear. Most mutations have little effect on an organism's phenotype, health, or reproductive fitness.[75] Mutations that do have an effect are usually detrimental, but occasionally some can be beneficial.[76] Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations will be harmful with the remainder being either neutral or weakly beneficial.[77]

text: Population genetics studies the distribution of genetic differences within populations and how these distributions change over time.[78] Changes in the frequency of an allele in a population are mainly influenced by natural selection, where a given allele provides a selective or reproductive advantage to the organism,[79] as well as other factors such as mutation, genetic drift, genetic draft,[80] artificial selection and migration.[81]

text: Over many generations, the genomes of organisms can change significantly, resulting in evolution. In the process called adaptation, selection for beneficial mutations can cause a species to evolve into forms better able to survive in their environment.[82] New species are formed through the process of speciation, often caused by geographical separations that prevent populations from exchanging genes with each other.[83] The application of genetic principles to the study of population biology and evolution is known as the "modern evolutionary synthesis."

text: By comparing the homology between different species' genomes, it is possible to calculate the evolutionary distance between them and when they may have diverged. Genetic comparisons are generally considered a more accurate method of characterizing the relatedness between species than the comparison of phenotypic characteristics. The evolutionary distances between species can be used to form evolutionary trees; these trees represent the common descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).[84]

text: Model organisms[edit]

text: Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research.[85] Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer.

text: Organisms were chosen, in part, for convenience—short generation times and easy genetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), and the common house mouse (Mus musculus).

text: Medicine[edit]

text: Medical genetics seeks to understand how genetic variation relates to human health and disease.[86] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a method especially useful for multigenic traits not clearly defined by a single gene.[87] Once a candidate gene is found, further research is often done on the corresponding (or homologous) genes of model organisms. In addition to studying genetic diseases, the increased availability of genotyping methods has led to the field of pharmacogenetics: the study of how genotype can affect drug responses.[88]

text: Individuals differ in their inherited tendency to develop cancer,[89] and cancer is a genetic disease.[90] The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process; signals are given to inappropriately dividing cells that should trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body.

text: Normally, a cell divides only in response to signals called growth factors and stops growing once in contact with surrounding cells and in response to growth-inhibitory signals. It usually then divides a limited number of times and dies, staying within the epithelium where it is unable to migrate to other organs. To become a cancer cell, a cell has to accumulate mutations in a number of genes (three to seven) that allow it to bypass this regulation: it no longer needs growth factors to divide, continues growing when making contact to neighbor cells, ignores inhibitory signals, keeps growing indefinitely and is immortal, escapes from the epithelium and ultimately may be able to escape from the primary tumor, cross the endothelium of a blood vessel, be transported by the bloodstream and colonize a new organ, forming deadly metastasis. Although there are some genetic predispositions in a small fraction of cancers, the major fraction is due to a set of new genetic mutations that originally appear and accumulate in one or a small number of cells that will divide to form the tumor and are not transmitted to the progeny (somatic mutations). The most frequent mutations are a loss of function of p53 protein, a tumor suppressor, or in the p53 pathway, and gain of function mutations in the Ras proteins, or in other oncogenes.

text: Research methods[edit]

text: DNA can be manipulated in the laboratory. Restriction enzymes are commonly used enzymes that cut DNA at specific sequences, producing predictable fragments of DNA.[91] DNA fragments can be visualized through use of gel electrophoresis, which separates fragments according to their length.

text: The use of ligation enzymes allows DNA fragments to be connected. By binding ("ligating") fragments of DNA together from different sources, researchers can create recombinant DNA, the DNA often associated with genetically modified organisms. Recombinant DNA is commonly used in the context of plasmids: short circular DNA molecules with a few genes on them. In the process known as molecular cloning, researchers can amplify the DNA fragments by inserting plasmids into bacteria and then culturing them on plates of agar (to isolate clones of bacteria cells – "cloning" can also refer to the various means of creating cloned ("clonal") organisms).

text: DNA can also be amplified using a procedure called the polymerase chain reaction (PCR).[92] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences.

text: DNA sequencing and genomics[edit]

text: DNA sequencing, one of the most fundamental technologies developed to study genetics, allows researchers to determine the sequence of nucleotides in DNA fragments. The technique of chain-termination sequencing, developed in 1977 by a team led by Frederick Sanger, is still routinely used to sequence DNA fragments.[93] Using this technology, researchers have been able to study the molecular sequences associated with many human diseases.

text: As sequencing has become less expensive, researchers have sequenced the genomes of many organisms using a process called genome assembly, which utilizes computational tools to stitch together sequences from many different fragments.[94] These technologies were used to sequence the human genome in the Human Genome Project completed in 2003.[34] New high-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars.[95]

text: Next-generation sequencing (or high-throughput sequencing) came about due to the ever-increasing demand for low-cost sequencing. These sequencing technologies allow the production of potentially millions of sequences concurrently.[96][97] The large amount of sequence data available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data. A common problem to these fields of research is how to manage and share data that deals with human subject and personally identifiable information. See also genomics data sharing.

text: Society and culture[edit]

text: On 19 March 2015, a leading group of biologists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited.[98][99][100][101] In April 2015, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[102][103]